morphine

Research Excerpts

Overview

Morphine is a drug of choice for the treatment of severe and chronic pain, but tolerance to the antinociceptive effect limits its use. Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED.

Excerpt	Reference	Relevance
"Morphine is a potent opioid analgesic with high propensity for the development of antinociceptive tolerance. "	( Morphine-induced kinase activation and localization in the periaqueductal gray of male and female mice. Bobeck, EN; Edwards, TM; McCarty, A; McDermott, MV; Ram, A, 2021)	3.51
"Morphine is a potent analgesic used to manage the pain following total knee arthroplasty (TKA). "	( Efficacy and safety of intrathecal morphine in total knee arthroplasty: A systematic review and meta-analysis. Abdelghany, EA; AbdelQadir, YH; Elmegeed, AA; Mohamed, AG; Nabhan, AE; Nourelden, AZ; Ragab, KM; Tokhey, ASE, )	1.85
"Morphine is an opioid drug often used in treating moderate to severe pain. "	( Cannabinoid Receptor Type 2 Agonist Reduces Morphine Tolerance via Mitogen Activated Protein Kinase Phosphatase Induction and Mitogen Activated Protein Kinase Dephosphorylation. Kong, Q; Ma, C; Tian, S; Wang, G; Zhang, M, 2022)	2.43
"Morphine is an analgesic agent used for cancer pain management. "	( Morphine promotes migration and lung metastasis of mouse melanoma cells. Abediny, R; Dana, N; Ghasemi, A; Javanmard, SH; Laher, I; Vaseghi, G, )	3.02
"IO morphine is a safe and effective method to lessen postoperative pain in TKA patients."	( Intraosseous Morphine Decreases Postoperative Pain and Pain Medication Use in Total Knee Arthroplasty: A Double-Blind, Randomized Controlled Trial. Brozovich, AA; Clyburn, TA; Incavo, SJ; Lambert, BS; Park, KJ; Sullivan, TC; Taraballi, F; Wininger, AE, 2022)	1.6
"Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. "	( Morphine analgesia in male inbred genetic diversity mice recapitulates the among-individual variance in response to morphine in humans. Guan, B; Meng, A; Wang, W; Wei, Q; Yang, Y, 2022)	3.61
"Morphine is a drug of choice for the treatment of severe and chronic pain, but tolerance to the antinociceptive effect limits its use. "	( Metformin prevents morphine-induced apoptosis in rats with diabetic neuropathy: a possible mechanism for attenuating morphine tolerance. Avci, O; Gursoy, S; Inan, ZDS; Ozdemir, E; Taskiran, AS, 2022)	2.49
"Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED."	( Efficacy and tolerability of oral morphine versus oxycodone/acetaminophen for analgesia in the emergency department. Brodie, K; Cacciapuoti, M; Gibson, C; Harvey, H; Mazer-Amirshahi, M; Motov, SM; Nelson, LS; Ramadan, L; Tefera, E; Yu, GG, )	0.92
"Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. "	( Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia. Avcı, O; Gunes, H; Gursoy, S; Inan, ZDS; Ozdemir, E; Taskiran, AS, 2023)	2.68
"Morphine is a potent analgesic opiate used to treat chronic pain, mostly in cancer patients. "	( Influence of chronic administration of morphine and its withdrawal on the behaviour of zebrafish. Agrewala, JN; Malik, JA; Nanda, S; Sehrawat, S; Zafar, MA, 2023)	2.62
"Morphine is a common analgesic often used to manage chronic pain, especially for patients with pain due to malignancies. "	( Roles of UGT2B7 C802T gene polymorphism on the efficacy of morphine treatment on cancer pain among the Chinese han population. Chen, Y; Guo, L; Hu, J; Hu, X; Ni, J; Ning, M; Shen, H; Tao, Y, 2019)	2.2
"Morphine tolerance is a classic, challenging clinical issue. "	( Liproxstatin-1 Attenuates Morphine Tolerance through Inhibiting Spinal Ferroptosis-like Cell Death. Chen, X; Feng, M; Liu, T; Wan, L; Yao, W; Zhang, B; Zhang, C; Zhang, Y, 2019)	2.26
"Morphine is a strong painkiller acting through mu-opioid receptor (MOR). "	( Morphine produces potent antinociception, sedation, and hypothermia in humanized mice expressing human mu-opioid receptor splice variants. Chang, HF; Chang, YC; Chuang, JY; Huang, YH; Loh, HH; Tao, PL; Wu, YW; Yeh, SH, 2020)	3.44
"Morphine is a natural alkaloid which derived from the opium poppy Papaver somniferum. "	( The neuroprotective effect of NeuroAid on morphine-induced amnesia with respect to the expression of TFAM, PGC-1α, ΔfosB and CART genes in the hippocampus of male Wistar rats. Hashemi, M; Malboosi, N; Nasehi, M; Vaseghi, S; Zarrindast, MR, 2020)	2.27
"Morphine is a potent analgesic agent used to control acute or chronic pain. "	( Melatonin and morphine: potential beneficial effects of co-use. Dehdashtian, E; Fatemi, I; Hemati, K; Hosseinzadeh, A; Mehrzadi, S; Pourhanifeh, MH; Reiter, RJ, 2021)	2.42
"Morphine pumps are a great help when patients in end-of-life stage cannot swallow oral morphine anymore."	( [Intensive treatment in family medicine : use of pumps and continuous glucose measurement systems]. Gastaldi, G; Jelk-Morales, L; Léocadie, F; Pautex, S; Sierro, C; Sommer, J, 2020)	1.28
"Morphine as an opioid is an important drug in the treatment of moderate to severe pain. "	( Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus. Akyuva, Y; Nazıroğlu, M; Osmanlıoğlu, HÖ; Yıldırım, MK; Yıldızhan, K, 2020)	3.44
"Morphine is a key drug for the treatment of pain but its side effects limit its clinical application. "	( Endomorphin analog exhibited superiority in alleviating neuropathic hyperalgesia via weak activation of NMDA receptors. Cui, J; Liu, X; Luo, K; Ma, M; Wang, J; Wang, R; Wang, Y; Wang, Z; Wei, S; Zhao, L, 2020)	2
"Morphine is a nonselective opioid receptor agonist that has been commonly used for analgesia and to treat ischaemic heart disease."	( Morphine and myocardial ischaemia-reperfusion. Hu, R; Wu, LN; Yu, JM, 2021)	2.79
"Morphine is an opiate alkaloid characterized by various clinical effects, among which the most prominent are its analgesic and psychoactive effects. "	( Cardiogenic shock induced by a high dose of intravenous morphine. Korolkiewicz, PK; Sein Anand, J; Sein Anand, Ł, 2021)	2.31
"Like morphine, methadone is a pure agonist at the µ opioid receptor. "	( Methadone: applications in pediatric anesthesiology and critical care medicine. Tobias, JD, 2021)	1.14
"Morphine is a commonly used opioid drug to treat acute pain by binding to the mu-opioid receptor (MOR), but its effective analgesic efficacy via triggering of the heterotrimeric G"	( Probing biased activation of mu-opioid receptor by the biased agonist PZM21 using all atom molecular dynamics simulation. Bong, D; Floyd, C; Liao, S; Pino, MJ; Tan, K; Wu, C, 2021)	2.06
"Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. "	( Morphine acts on spinal dynorphin neurons to cause itch through disinhibition. Ding, H; Hachisuka, J; Ko, MC; Lim, G; Nguyen, E; Ross, SE, 2021)	3.51
"Morphine is an opioid agonist and a nonselective mu, kappa and delta receptor agonist. "	( Involvement of TCF7L2 in generation of morphine-induced antinociceptive tolerance and hyperalgesia by modulating TLR4/ NF-κB/NLRP3 in microglia. Chen, J; Huo, X; Kong, Y; Ma, C; Sun, T; Wang, G, 2021)	2.33
"Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. "	( Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children. de Wildt, SN; Koenderink, JB; Litjens, CHC; Mathijssen, RHJ; Russel, FGM; Verbeek, MM; Verscheijden, LFM, 2021)	2.29
"Morphine (MOR) is a strong analgesic that is often used in treatment of severe pains during cancer treatment, and thus might be concomitantly used with anticancer drugs as cisplatin (CP). "	( Morphine Deteriorates Cisplatin-Induced Cardiotoxicity in Rats and Induces Dose-Dependent Cisplatin Chemoresistance in MCF-7 Human Breast Cancer Cells. El-Sheikh, AAK; Khired, Z, 2021)	3.51
"Morphine is an opioid analgesic indicated in the treatment of acute and chronic moderate to severe pain. "	( Pharmacogenomics and Morphine. B Ettienne, E; Ofoegbu, A, 2021)	2.38
"Morphine is an opioid pain killer and a strong analgesic that is used to treat chronic pain."	( Morphine attenuates neurotoxic effects of MPTP in zebrafish embryos by regulating oxidant/antioxidant balance and acetylcholinesterase activity. Alturfan, AA; Cansız, D; Emekli-Alturfan, E; Unal, I; Ustundag, UV, 2022)	2.89
"Morphine tolerance is a clinical challenge in pain management. "	( miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats. Ding, Z; Guo, Q; He, Z; Huang, J; Shao, J; Wang, J; Xu, W; Zou, W, 2017)	2.17
"Morphine (MOR) is an opiate alkaloid widely used to treat severe acute and chronic pain."	( Application of 1-Dimensional and 2-Dimensional Solid-State Nuclear Magnetic Resonance Spectroscopy to the Characterization of Morphine, Morphine Hydrochloride, and Their Hydrates. Alves de Santana, MS; Ayala, AP; Chattah, AK; Garro-Linck, Y; Manzo, RH; Monti, GA; Olivera, ME; Romañuk, CB, 2017)	1.38
"Morphine is a widely used analgesic for various types of pain. "	( Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats. Fan, Y; Liang, X; Song, L; Wang, R, 2017)	2.11
"Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). "	( Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord. Han, Y; Hu, L; Jiang, CY; Liu, WT; Qian, Y; Qu, J; Tao, GJ; Zhang, G; Zhang, Y, 2017)	2.22
"Morphine is a well-characterized and effective analgesic commonly used to provide pain relief to patients suffering from both acute and chronic pain conditions. "	( PolyMorphine provides extended analgesic-like effects in mice with spared nerve injury. Chen, R; Kolber, B; Lax, NC; Leep, SR; Uhrich, K; Yu, L, )	2.13
"Morphine is a representative pain killer. "	( Music therapy inhibits morphine-seeking behavior via GABA receptor and attenuates anxiety-like behavior induced by extinction from chronic morphine use. Kim, KJ; Lee, BH; Lee, SN, 2018)	2.23
"Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment, but the mechanisms of morphine tolerance remain unclear. "	( Identification of lncRNA expression profiles and ceRNA analysis in the spinal cord of morphine-tolerant rats. Guo, Q; Huang, J; Liu, C; Pan, Y; Shao, J; Wang, J; Zou, W, 2018)	2.15
"Morphine is a molecule of great cultural relevance, as the agent that single-handedly transformed our understanding of pharmacognosy, receptor dynamics, and substance abuse and dependence disorders."	( DARK Classics in Chemical Neuroscience: Morphine. Cunningham, CW; Devereaux, AL; Mercer, SL, 2018)	1.47
"Morphine is an opioid alkaloid commonly used in clinical practice for its analgesic properties. "	( Morphine, a potential inhibitor of myeloperoxidase activity. Franck, T; Hoebeke, M; Minguet, G; Mouithys-Mickalad, A; Nyssen, P; Sauvage, E; Wouters, J, 2018)	3.37
"Morphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. "	( Relative Oral Bioavailability of an Abuse-deterrent, Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period, Single-dose, Randomized Crossover Study in Healthy Subjects. Aigner, S; Kinzler, ER; Pantaleon, C, 2018)	2.15
"Morphine is an analgesic drug therapeutically administered to relieve pain. "	( The Impact of Morphine on the Characteristics and Function Properties of Human Mesenchymal Stem Cells. Bohacova, P; Cechova, K; Hajkova, M; Hermankova, B; Holan, V; Javorkova, E; Kossl, J; Krulova, M; Svoboda, P; Zajicova, A, 2018)	2.28
"Morphine is a substrate of OCT1 and OCT2. "	( Irinotecan Alters the Disposition of Morphine Via Inhibition of Organic Cation Transporter 1 (OCT1) and 2 (OCT2). Guo, D; Guo, J; Huang, S; Li, Q; Polli, JE; Shu, Y; Xiong, Z; Ye, Z; Zhang, W; Zhou, H; Zhu, P, 2018)	2.2
"Morphine-induced CPP is a common method to consider motivational properties of morphine in animals."	( Intra-hippocampal administration of orexin receptor antagonists dose-dependently attenuates reinstatement of morphine seeking behavior in extinguished rats. Alizamini, MM; Fatahi, Z; Haghparast, A; Karimi-Haghighi, S; Kavianpour, M, 2018)	1.41
"Morphine is a classic opioid drug used for reducing pain and is commonly prescribed as an effective drug to control cancer pain. "	( The dual effect of morphine on tumor development. Cui, J; Tuerxun, H, 2019)	2.29
"Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. "	( Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia. Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Dudink, J; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019)	2.28
"Morphine is a unique opioid analgesic that activates the mu-opioid receptor (MOR) without efficiently promoting its endocytosis that may underlie side effects. "	( Convallatoxin enhance the ligand-induced mu-opioid receptor endocytosis and attenuate morphine antinociceptive tolerance in mice. Chang, HF; Chang, WT; Chao, PK; Chen, SC; Chuang, JY; Hsu, JT; Law, PY; Lee, PT; Loh, HH; Ou, LC; Tao, PL; Ueng, SH; Yeh, SH, 2019)	2.18
"Morphine is a potent analgesic for cancer pain, and radiation therapy is a conventional treatment for cancer."	( Evaluation of effects of morphine and ionizing radiation in cancer cell lines. Amooheidari, A; Javanmard, SH; Naderi, J; Samani, F; Vahabzadeh, G; Vaseghi, G, 2019)	1.54
"Morphine is a potent opioid analgesic used to alleviate moderate or severe pain, but the development of drug tolerance and dependence limits its use in pain management. "	( The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence. Li, F; Li, J; Li, S; Lu, GY; Wang, ZY; Wu, N; Zhao, TY, 2019)	2.2
"Morphine tolerance is an adaptive process induced by chronic morphine that has been shown to result from complex alterations at the molecular level with"	( The Emerging Perspective of Morphine Tolerance: MicroRNAs. Hua, Z; Qiu, Y; Zhang, TJ, 2019)	1.53
"Morphine is a potent analgesic, but its molecular mechanism for tolerance formation is not fully understood. "	( [Endoplasmic reticulum stress and opioid tolerance withdrawal]. Aoe, T, 2013)	1.83
"Morphine was found to be a reasonable alternative to haloperidol in the treatment of postoperative hyperactive delirious patients after cardiac surgery."	( Morphine is a reasonable alternative to haloperidol in the treatment of postoperative hyperactive-type delirium after cardiac surgery. Akgün, S; Atalan, N; Başaran, C; Efe Sevim, M; Fazlıoğulları, O, 2013)	2.55
"Morphine is a transporter substrate at the human blood-brain barrier. "	( Cyclosporine-inhibitable blood-brain barrier drug transport influences clinical morphine pharmacodynamics. Avram, MJ; Blood, J; Francis, AM; Kharasch, ED; Meissner, K; Yermolenka, V, 2013)	2.06
"Morphine is a classic analgesic for the treatment of chronic pain. "	( An integrated quantitative proteomics and systems biology approach to explore synaptic protein profile changes during morphine exposure. Devi, LA; Stockton, SD, 2014)	2.05
"Morphine is a potent agonist of μ-opioid receptor and is widely used to relieve severe pain, including cancer pain. "	( Activation of CXCL10/CXCR3 signaling attenuates morphine analgesia: involvement of Gi protein. Bu, H; Gao, F; Guan, X; Guo, G; Shu, B; Tian, X; Wang, W; Xiang, H; Yang, H; Ye, D, 2014)	2.1
"Morphine is an opioid agonist widely used to treat severe and chronic pain, as for example cancer pain."	( Morphine modulates cell proliferation through mir133b &mir128 in the neuroblastoma SH-SY5Y cell line. Gonzalez-Nunez, V; Noriega-Prieto, JA; Rodríguez, RE, 2014)	2.57
"Morphine is a commonly encountered opiate in postmortem toxicology known to have stable blood concentrations in peripheral vessels."	( Morphine concentrations in skeletal muscle. Hargrove, VM; Molina, DK, 2014)	2.57
"Morphine is an opioid compound exhibiting special antagonistic interaction with 5-HT3A receptors. "	( Direct effects of morphine but not of fentanyl-type opioids on human 5-HT3A receptors in outside-out patch-clamp studies. Lyutenska, M; Schaaf, T; Urban, BW; Wittmann, M, 2014)	2.18
"Morphine appears to be an acceptable breathlessness treatment option to these people with CHF."	( Attitudes to morphine in chronic heart failure patients. Clark, AL; Johnson, MJ; Jones, L; Oxberry, SG, 2012)	1.47
"Morphine is a known substrate of P-glycoprotein (P-gp) at the blood-brain-barrier (BBB) however, little is known about the interaction of heroin and 6-MAM with P-gp."	( Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties. Chapy, H; Chiadmi, F; Cisternino, S; Courtin, C; Marie-Claire, C; Noble, F; Scherrmann, JM; Schlatter, J; Seleman, M; Smirnova, M, 2014)	1.12
"Morphine is a potent analgesic opioid used extensively for pain treatment. "	( Therapeutic concentration of morphine reduces oxidative stress in glioma cell line. Almeida, MB; Costa-Malaquias, A; Crespo-López, ME; Herculano, AM; Nascimento, JL; Oliveira, KR, 2014)	2.14
"Morphine is a commonly prescribed and commonly encountered opiate medication that is often found in postmortem examinations, both as a cause of death and also as an incidental finding."	( Peripheral postmortem redistribution of morphine. Hargrove, VM; Molina, DK, 2014)	1.39
"Morphine is a major option for pain management; its global consumption more than quadrupled in the last decade."	( Morphine protects against methylmercury intoxication: a role for opioid receptors in oxidative stress? Almeida, MB; Costa-Malaquias, A; Crespo-Lopez, ME; do Nascimento, JL; Macchi, Bde M; Souza Monteiro, JR, 2014)	2.57
"Morphine is an opioid analgesic drug commonly used for pain relief in cancer patients. "	( Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer. Gao, P; Guan, Z; Han, QN; Li, JL; Li, TT; Liu, Q; Niu, DG; Peng, F; Wang, KL; Wen, QP; Xu, F; Zhang, W; Zhang, Y; Zhao, HD; Zheng, FM, 2015)	3.3
"Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children."	( A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose. Aleksa, K; Carleton, BC; Castañeda-Hernandez, G; Cooke, E; Dawes, J; Gonzalez-Ramirez, R; Jacobo-Cabral, CO; Jimenez-Mendez, R; Koren, G; Montgomery, CJ; Rieder, MJ; Velez de Mendizabal, N, 2015)	1.16
"Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. "	( A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain. Christrup, LL; Drewes, AM; Kreilgaard, M; Lund, TM; Olesen, AE; Sverrisdóttir, E, 2015)	2.24
"Morphine is a psychoactive medication that is used as a standard analgesic treatment to relieve pain in clinics. "	( Investigation of genes in chronic and acute morphine-treated mice using microarray datasets. Ding, L; Sheng, LF; Yu, SH; Zhang, JL, 2015)	2.12
"Morphine is an opioid analgesic drug often used for pain relief in cancer patients. "	( Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Cao, LH; Li, HT; Lin, WQ; Tan, HY; Xie, L; Zhong, ZJ; Zhou, JH, 2016)	3.32
"Morphine is a well-known opioid used to treat different types of pain."	( Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. Go, D; Kim, MJ; Kim, SK; Kim, W; Min, BI; Na, HS, 2016)	1.41
"Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain."	( A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study. Dirksen, CD; Franssen, FM; Janssen, DJ; Schols, JM; van den Beuken-van Everdingen, MH; Verberkt, CA; Wouters, EF, 2016)	1.38
"Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known."	( Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats. Akella, A; Deshpande, SB; Rai, OP; Tiwari, AK, )	2.3
"Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. "	( Metabolism and pharmacokinetics of morphine in neonates: A review. Pacifici, GM, 2016)	2.15
"Morphine is an opioid analgesic drug often used for pain relief in cancer patients. "	( Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level. Ding, P; He, M; Ma, S; Ma, Y; Ren, Z; Wang, D; Yan, W, 2017)	3.34
"Morphine is a μ-opioid analgesic drug which is used in the treatment and management of chronic pain. "	( Thalidomide attenuates the development and expression of antinociceptive tolerance to μ-opioid agonist morphine through l-arginine-iNOS and nitric oxide pathway. Dehpour, AR; Ejtemaei-Mehr, S; Hassanipour, M; Khan, MI; Moghaddaskho, F; Momeny, M; Mumtaz, F; Ostadhadi, S, 2017)	2.11
"Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. "	( miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats. Ding, Z; Dong, X; Guo, Q; Song, Z; Wang, J; Xu, W; Zhong, T; Zou, W; Zou, Y, 2016)	2.14
"Morphine is an opioid analgesic used to relieve moderate-to-severe pain, including pain in neonates at the intensive care unit. "	( Morphine exposure during early life alters thermal and mechanical thresholds in rats. Caumo, W; de Freitas, JS; de Souza, A; Kuo, J; Macedo, IC; Medeiros, LF; Nunes, EA; Rozisky, JR; Torres, ILS, 2017)	3.34
"Morphine is a well-known mu-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. "	( Improvement of morphine-mediated analgesia by inhibition of β-arrestin2 expression in mice periaqueductal gray matter. Kang, J; Li, Y; Liu, C; Liu, X; Pei, G; Wu, C; Yang, J, 2009)	2.15
"Morphine sensitization is a model of latent, functionally inducible increase in dopamine D(1) receptor-mediated transmission, which may be unmasked by an external stimulus. "	( Dopamine D1 receptor-dependent modifications in the dopamine and cAMP-regulated phosphoprotein of Mr 32 kDa phosphorylation pattern in striatal areas of morphine-sensitized rats. Crociani, A; De Montis, MG; Gambarana, C; Scheggi, S; Tagliamonte, A, 2009)	1.99
"Morphine is a powerful analgesic natural product produced by the opium poppy Papaver somniferum. "	( CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy. Díaz Chávez, ML; Gesell, A; Huang, FC; Kutchan, TM; Rolf, M; Ziegler, J, 2009)	2.03
"Morphine is a mu-opioid receptor agonist commonly used for pain treatment but is associated with side effects that can be serious."	( NT69L, a novel analgesic, shows synergy with morphine. Barbut, D; Boules, M; Liang, Y; Richelson, E; Shaw, A, 2009)	1.33
"Morphine is an analgesic drug used to treat acute and chronic pain. "	( Pharmacology of morphine in obese patients: clinical implications. Bardin, C; Basdevant, A; Bergmann, JF; Clement, K; Declèves, X; Lepine, JP; Lloret Linares, C; Mouly, S; Oppert, JM; Scherrmann, JM, 2009)	2.14
"Morphine is a potent analgesic, but the molecular mechanism for tolerance formation after repeated use is not fully understood. "	( BiP, an endoplasmic reticulum chaperone, modulates the development of morphine antinociceptive tolerance. Aoe, T; Dobashi, T; Jin, H; Mimura, N; Nishino, T; Tanabe, S; Yamamoto, T, 2010)	2.04
"Morphine is a commonly prescribed analgesic for wound pain. "	( Morphine enhances tissue content of collagen and increases wound tensile strength. Chang, PJ; Chen, MY; Huang, CC; Huang, YS; Lam, CF; Lee, CH; Tsai, YC, 2010)	3.25
"Morphine is a potent opioid analgesic. "	( Valproate attenuates the development of morphine antinociceptive tolerance. Aoe, T; Dobashi, T; Jin, H; Nishino, T; Tanabe, S, 2010)	2.07
"Morphine is a widely used analgesic in humans that is associated with multiple untoward effects, such as addiction and physical dependence. "	( A dopamine D1 receptor-dependent β-arrestin signaling complex potentially regulates morphine-induced psychomotor activation but not reward in mice. Caron, MG; Daigle, TL; Urs, NM, 2011)	2.04
"Morphine is an analgesic widely used to alleviate cancer pain. "	( Morphine and tumor growth and metastasis. Afsharimani, B; Cabot, P; Parat, MO, 2011)	3.25
"Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process."	( Does sleep deprivation and morphine influence wound healing? Andersen, ML; Egydio, F; Tomimori, J; Tufik, S, 2011)	1.39
"Morphine is an antagonist at 5-HT(3) A receptors. "	( The 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by morphine. Baptista-Hon, DT; Deeb, TZ; Hales, TG; Othman, NA; Sharp, D, 2012)	2.05
"Morphine is a highly potent analgesic with high addictive potential in specific contexts. "	( Neuronal circuits underlying acute morphine action on dopamine neurons. Barrot, M; Bourdy, R; Courtin, J; Georges, F; Jalabert, M; Manzoni, OJ; Veinante, P, 2011)	2.09
"Morphine is a drug commonly administered via the epidural or intrathecal route, and is regarded by many as the 'gold-standard' single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action. "	( Neuraxial morphine and respiratory depression: finding the right balance. Carvalho, B; Gutierrez, MC; Sultan, P, 2011)	2.21
"Morphine is a widely used drug for analgesia and substance abuse. "	( Influence of morphine on host immunity. Chang, MC; Cheng, WF; Fan, SZ; Hsiao, PN; Sun, WZ, 2011)	2.18
"Morphine is a potent and effective analgesic, but substance abuse patients can manifest cross-tolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements."	( Carbamazepine potentiates morphine analgesia on postoperative pain in morphine-dependent rats. Moini Zanjani, T; Naseri, K; Sabetkasaei, M; Saghaei, E, 2012)	1.4
"Morphine is a widely abused, addictive drug that modulates immune function. "	( Morphine and galectin-1 modulate HIV-1 infection of human monocyte-derived macrophages. Aalinkeel, R; Hui, R; Law, WC; Mahajan, SD; Mammen, MJ; Nair, B; Prasad, PN; Reynolds, JL; Schwartz, SA; Sykes, DE; Yong, KT, 2012)	3.26
"Morphine is a drug with immunosuppressant properties whose chronic use may lead to increased infection and delayed wound healing."	( Influence of sleep deprivation and morphine on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in skin of hairless mice. Andersen, ML; Egydio, F; Noguti, J; Ribeiro, DA; Tufik, S, 2012)	1.38
"Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. "	( Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance. Derong, C; Jing, W; Li, W; Moxi, C; Quanhong, Z; Tao, X; Wei, J; Xiaoli, Z; Xin, Z; Ying, X, 2012)	2.06
"Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process."	( Can morphine interfere in the healing process during chronic stress? Andersen, ML; Egydio, F; Ruiz, FS; Tomimori, J; Tufik, S, 2012)	1.66
"Morphine tolerance is a common drawback of chronic morphine exposure, hindering use of this drug. "	( Proteomic analysis of PKCγ-related proteins in the spinal cord of morphine-tolerant rats. Guo, Q; Li, M; Liu, C; Song, Z; Zhang, J; Zou, W, 2012)	2.06
"Morphine is an important drug used to alleviate moderate to severe pain. "	( Inhibition of morphine glucuronidation in the liver microsomes of rats and humans by monoterpenoid alcohols. Iida, N; Ishii, Y; Mackenzie, PI; Miyauchi, Y; Yamada, H, 2012)	2.18
"Morphine is a powerful analgesic but its effect is often diminished owing to the development of tolerance. "	( Microglial activation involved in morphine tolerance is not mediated by toll-like receptor 4. Fukagawa, H; Fukuda, K; Kakuyama, M; Koyama, T, 2013)	2.11
"Morphine is an opioid commonly used in children to manage perioperative pain."	( Morphine clearance in children: does race or genetics matter? Chidambaran, V; Esslinger, HR; Fukuda, T; Krekels, EH; Ngamprasertwong, P; Sadhasivam, S; Vinks, AA; Zhang, K, )	2.3
"Morphine is an effective analgesic that acts by binding to the µ-opioid receptor (MOR) coded in the human by the OPRM1 gene. "	( Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine. Badisa, RB; Goodman, CB; Luscar, E; Prenus, RV; Zhu, ZP, 2012)	2.04
"Morphine is a gold standard analgesic commonly used to alleviate pain. "	( Antinociceptive effect of intrathecal loperamide: role of mu-opioid receptor and calcium channels. Kumar, R; Ray, SB; Reeta, KH, 2012)	1.82
"Oral morphine is a recommended option for the treatment of neonatal abstinence syndrome (NAS). "	( Stability of dilute oral morphine solution for neonatal abstinence syndrome. Kim, JH; Rossi, S; Sauberan, J, )	0.95
"Morphine is a widely used analgesic in management of postoperative pain with well documented analgesic properties and side effects. "	( [Comparison of postoperative analgesia with tramadol, morphine versus their combination in patients undergoing abdominal cancer surgery]. Li, W; Lin, WQ; Xu, MX; Zeng, WA; Zhong, ZJ, 2002)	2.01
"Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver."	( Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. Armstrong, SC; Cozza, KL, )	1.13
"Diamorphine is a semisynthetic derivative of morphine that is currently licensed for use in the treatment of moderate to severe acute pain, administered by the intramuscular, intravenous or subcutaneous routes. "	( Intranasal diamorphine as an alternative to intramuscular morphine: pharmacokinetic and pharmacodynamic aspects. Kendall, JM; Latter, VS, 2003)	1.3
"Morphine was shown to be an effective analgesic."	( Oral morphine for cancer pain. Barden, J; Edwards, JE; McQuay, HJ; Wiffen, PJ, 2003)	1.55
"Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals."	( Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Hoffer, C; Kharasch, ED; Sheffels, P; Whittington, D, 2003)	1.27
"Morphine is a poor inducer of micro-opioid receptor (MOR) internalization, but a potent inducer of cellular tolerance. "	( Morphine induces terminal micro-opioid receptor desensitization by sustained phosphorylation of serine-375. Höllt, V; Koch, T; Mayer, D; Pfeiffer, M; Schulz, S; Stumm, R, 2004)	3.21
"Morphine is a preferred narcotic since meperidine forms toxic metabolites. "	( Determinants of prescribing meperidine compared to morphine in hospitalized patients. Desbiens, N; Doshi, N; Panda, M; Sheldon, S, 2004)	2.02
"Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. "	( Endogenous formation of morphine in human cells. Brandsch, M; Dräger, B; Poeaknapo, C; Schmidt, J; Zenk, MH, 2004)	2.07
"Morphine is an effective analgesic, but adverse effects limit its clinical use in higher doses. "	( Dextromethorphan potentiates morphine antinociception at the spinal level in rats. Chow, LH; Ho, ST; Huang, EY; Lee, TY; Tao, PL, 2004)	2.06
"Morphine is a strong and widely used opioid analgesic in pain management, but some adverse effects limit its clinical use at high doses. "	( Dextromethorphan potentiates morphine-induced antinociception at both spinal and supraspinal sites but is not related to the descending serotoninergic or adrenergic pathways. Chow, LH; Ho, ST; Huang, EY; Tao, PL; Tsai, SK, )	1.87
"Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. "	( Morphine side effects in beta-arrestin 2 knockout mice. Bohn, LM; Raehal, KM; Walker, JK, 2005)	3.21
"Morphine is an exceptionally effective analgesic whose utility is compromised by the development of tolerance and dependence to the drug. "	( An opiate cocktail that reduces morphine tolerance and dependence. He, L; Whistler, JL, 2005)	2.05
"Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily."	( Opiate therapy in chronic cough. Everett, CF; Jackson, J; Menon, MS; Morice, AH; Mulrennan, SA; Thompson, R; Wright, C, 2007)	1.78
"Morphine is an opiate drug widely used as an analgesic in multiple medical diseases. "	( [Morphine maintenance treatment in opiate dependent patients]. Casas Brugué, M; Castells Cervelló, X; Roncero Alonso, C; Sáez Francàs, N, 2007)	2.69
"Morphine is an analgesic drug used for the treatment of acute and chronic pain syndromes for cancer patients. "	( Morphine glucuronosyltransferase activity in human liver microsomes is inhibited by a variety of drugs that are co-administered with morphine. Hara, Y; Miyamoto, K; Nakajima, M; Yokoi, T, 2007)	3.23
"Morphine was shown to be an effective analgesic."	( Oral morphine for cancer pain. McQuay, HJ; Wiffen, PJ, 2007)	1.57
"Morphine is a prototypical mu-opioid receptor (MOR) agonist, and can directly inhibit pain transmission at both spinal and supraspinal levels. "	( Post-synaptic action of morphine on glutamatergic neuronal transmission related to the descending antinociceptive pathway in the rat thalamus. Amano, T; Hashimoto, K; Nakamura, A; Narita, M; Niikura, K; Suzuki, T, 2008)	2.1
"Morphine is a better drug as compared to tramadol for attenuation of laryngoscopy and endotracheal intubation response."	( Haemodynamic response of intravenous tramadol and intravenous morphine during laryngoscopy and endotracheal intubation. Abbas, MQ; Hoda, MQ; Khan, MU; Sabir, S, 2008)	2.03
"Morphine is a long-standing therapy in acute decompensated heart failure (ADHF), despite few supporting data. "	( Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis. Diercks, DB; Emerman, CL; Fonarow, G; Hollander, JE; Lopatin, M; Peacock, WF, 2008)	3.23
"Morphine is a standard medication in pain therapy; opioids are grouped in step two and three of the WHO analgesic ladder. "	( [Does morphine have a life-shortening effect?]. Baust, G, 2008)	2.27
"Morphine chloride is a more potent inhibitor of 3H-ethylketocyclazocine binding and tritiated mu ligand in hypotonic Tris-HCl buffer than in isotonic HEPES buffer."	( The effect of two different buffers on the high affinity 3H-ethylketocyclazocine and 3H-SKF10047 binding to guinea pig brain membranes. Enger, M; Grynne, BH; Holmen, AT; Maurset, AR, 1984)	0.99
"Morphine sulfate is a weak analgesic in the frog Rana pipiens pipiens, causing a slight increase in nociceptive threshold at a dose of 10 mg/kg and a pronounced increase at 100 mg/kg. "	( Morphine-induced analgesia and explosive motor behavior in an amphibian. Pezalla, PD, 1983)	3.15
"Morphine is a relatively poorly lipophilic opioid but equilibrates with tissue of the brain relatively easily."	( 1994 John J. Bonica Lecture. The clinical effects of morphine pharmacology. Mather, LE, )	1.1
"Morphine dependence is a long lasting form of neuronal plasticity. "	( Precipitated morphine withdrawal stimulates multiple activator protein-1 signaling pathways in rat brain. Couceyro, P; Douglass, J, 1995)	2.1
"Morphine is a drug of abuse with an ability to down-regulate immune responsiveness that could have potentially serious consequences in both heroin addicts and in the clinical environment. "	( A mechanism of action for morphine-induced immunosuppression: corticosterone mediates morphine-induced suppression of natural killer cell activity. Freier, DO; Fuchs, BA, 1994)	2.03
"Morphine is a potent analgesic when microinjected into the periaqueductal gray (PAG), the rostral ventral medulla (RVM) which contains the nuclei raphe magnus and reticularis gigantocellularis and the dorsolateral pons (DLP) which includes the locus coeruleus. "	( Synergistic brainstem interactions for morphine analgesia. Bodnar, RJ; Pasternak, GW; Rossi, GC, 1993)	2
"Morphine-6-glucuronide is a metabolite of morphine that shows significant analgesic effects in animals and humans. "	( Disposition of morphine and its glucuronide metabolites after oral and rectal administration: evidence of route specificity. Babul, N; Darke, AC, 1993)	2.08
"Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long-term treatment of severe pain. "	( Morphine metabolites. Christrup, LL, 1997)	3.18
"Morphine is an analgesic agent used for the symptomatic relief of moderate to severe pain. "	( Preparation and use of morphine capsules in paediatric patients with burns. Amirat-Combralier, V; Balansard, G; Bues-Charbit, M; Dejode, JM; Elias, R; Jentile, B; Lagier, P, )	1.88
"Morphine is a potent inhibitor of nocturnal uterine contractions (UCs) in the pregnant baboon, and these contractions are known to be induced by oxytocin (OT). "	( Morphine inhibits nocturnal oxytocin secretion and uterine contractions in the pregnant baboon. Kowalski, WB; Pak, SC; Parsons, MT; Wilson, L, 1998)	3.19
"Morphine is a potent analgesic and is widely used in the clinical management of severe acute and chronic pain; however, its clinical usefulness is limited due to the development of both tolerance and dependence after repeated morphine administration. "	( [Production of morphinone as a metabolite of morphine and its physiological role]. Toki, S; Yamano, S, 1999)	2.01
"Morphine is a widely used analgesic for the treatment of severe cancer pain. "	( Stability and compatibility of morphine. Remon, JP; Vermeire, A, 1999)	2.03
"Morphine is an agonist of mu-opioid receptors and inhibits N-type VSCC channels via a G-protein coupling mechanism."	( Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats. Bowersox, SS; Gao, D; Pettus, M; Phillips, C; Wang, YX, 2000)	1.23
"Morphine (MOR) is an opioid analgesic used for the treatment of moderate to severe pain. "	( Simultaneous assay of morphine, morphine-3-glucuronide and morphine-6-glucuronide in human plasma using normal-phase liquid chromatography-tandem mass spectrometry with a silica column and an aqueous organic mobile phase. Hulse, JD; Jiang, X; Lee, JW; Lin, PP; Naidong, W; Wehling, M, 1999)	2.06
"Morphine is an effective training drug in drug discrimination procedures. "	( Morphine discriminative control is mediated by the mu opioid receptor: assessment of delta opioid substitution and antagonism. Cañadas, F; Rice, KC; Riley, AL; Stevenson, GW; Zhang, X, 2000)	3.19
"Morphine itself acts as a chemokinetic factor for fish leucocytes as it increases their random movements."	( Inhibitory effects of morphine on some inflammation-related parameters in the goldfish Carassius auratus L. Chadzinska, M; Plytycz, B; Scislowska-Czarnecka, A, 2000)	1.34
"Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. "	( Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Bohn, LM; Caron, MG; Gainetdinov, RR; Lefkowitz, RJ; Lin, FT, 2000)	1.99
"Morphine is a known substrate for rat UGT2B1 and human UGT2B7 and both total morphine glucuronidation (3-O- and 6-O-glucuronides) and diclofenac glucuronidation reactions showed a strong correlation with one another in human liver microsome samples."	( Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac. Braun, M; King, C; Ngui, J; Tang, W; Tephly, T, 2001)	1.03
"Morphine is a principal axis in drug therapy of pain, especially at the end stage of cancer."	( [Effects of morphine on cancer pain and tumor growth and metastasis]. Kuraishi, Y, 2001)	1.41
"morphine is a naloxone-sensitive, centrally mediated event not associated with activation of the central emetic mechanism."	( Centrally mediated intestinal stimulation by morphine. Burks, TF; Stewart, JJ; Weisbrodt, NW, 1977)	1.24
"Morphine-6-glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. "	( The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function. Foley, KM; Friedlander-Klar, H; Inturrisi, CE; Portenoy, RK; Thaler, HT, 1992)	2.08
"Morphine was confirmed to be a metabolite of pholcodine by reversed-phase chromatography and electrochemical detection."	( Column-switching high-performance liquid chromatographic detection of pholcodine and its metabolites in urine with fluorescence and electrochemical detection. Johansen, M; Rasmussen, KE; Tønnesen, F, 1992)	1
"Morphine is a very safe drug, correctly prescribed in chronic pain therapy, the only severe side effect being constipation."	( Morphine myths: sedation, tolerance, addiction. Zenz, M, 1991)	2.45
"Morphine is a key drug for cancer pain management. "	( Relationship between plasma concentration of morphine and analgesic effectiveness. Hiraga, K; Konishi, M; Oguma, T; Yokokawa, N, 1991)	1.98
"Morphine-6-glucuronide is an active metabolite of morphine that has analgesic properties and is measurable in the plasma and cerebrospinal fluid of patients treated with this opioid. "	( Chronic nausea and morphine-6-glucuronide. Cerbone, DJ; Foley, KM; Hagen, NA; Inturrisi, CE; Portenoy, RK, 1991)	2.05
"Morphine acts as a strong agonist with an EC50 of 50 to 100 nM which falls into the therapeutic range expected for narcotic analgesic effects mediated by the mu receptor."	( Efficacy and tolerance of narcotic analgesics at the mu opioid receptor in differentiated human neuroblastoma cells. Sadée, W; Yu, VC, 1988)	1

Effects

Morphine has a variety of actions on the release of pituitary hormones in addition to its analgesic actions. Morphine withdrawal has a manifest harm in hippocampal CA1 region of rat.

Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines.

Excerpt	Reference	Relevance
"Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. "	( The Dopaminergic System in the Ventral Tegmental Area Contributes to Morphine Analgesia and Tolerance. Gao, F; Li, Z; Tu, Y; Wang, J, 2023)	2.59
"Morphine has a phenolic and an alcoholic OH group, while codeine bears only an alcoholic OH group. "	( Using gas-phase chloride attachment for selective detection of morphine in a morphine/codeine mixture by ion mobility spectrometry. Ilbeigi, V; Valadbeigi, Y, 2021)	2.3
"Morphine has a direct role in the central nervous system to relieve pain, but because of its peripheral functions, morphine also has some side effects, such as nausea, constipation, and addiction (Gupta et al."	( The dual effect of morphine on tumor development. Cui, J; Tuerxun, H, 2019)	1.56
"Morphine has a profound role in neurofilament (NF) expression. "	( Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence. Das, S; Pal, A, 2015)	3.3
"Morphine chloride has an inhibitory effect on the contractility of rabbit small intestine in vitro or in vivo. "	( [Effect of morphine chloride on contractility of small intestinal muscle in vitro or in vivo and its mechanisms]. Feng, ZY; Lu, Y; Mao, LG, 2008)	2.18
"Morphine withdrawal has a manifest harm in hippocampal CA1 region of rat."	( [The expression of BDNF and PSD-95 in hippocampal CA1 region of morphine-withdrawn rat with different dependent times]. Chen, GD; Chen, P; Han, JG; Liu, XN; Luo, LM; Wang, CB; Zhu, H, 2008)	1.31
"Morphine has a negative effect on Th cell balance induced by PMA and ionomycin, the mechanism is related to T-bet and GATA3."	( Morphine, but not ketamine, decreases the ratio of Th1/Th2 in CD4-positive cells through T-bet and GATA3. Gao, M; Jin, W; Qian, Y; Sun, J, 2012)	2.54
"As morphine has a vasopressin releasing and a brain L-asparaginase inhibiting effect the antidiuretic action of morphine was considered to be linked to its inhibitory effect on the brain L-asparaginase."	( Vasopressin release by D-aspartic acid, morphine and prolyl-leucyl-glycinamide (PLG) in DI Brattleboro rats. Berkman, K; Hatipoğlu, I; Koyuncuoğlu, H; Sabuncu, H, 1984)	1.05
"Morphine has a variety of actions on the release of pituitary hormones in addition to its analgesic actions. "	( Different receptors mediate morphine-induced prolactin and growth hormone release. Kourides, IA; Pasternak, GW; Spiegel, K, )	1.87
"Morphine has a significant protective effect on ethanol-induced gastric lesions. "	( Gastric cytoprotective effect of morphine is probably not mediated by mu-receptors. Bhounsule, SA; D'Souza, RS; Dhume, VG, )	1.86
"Morphine augmentation has a reasonably good, though imperfect, specificity and positive predictive value, that are significantly better than for delayed imaging, in addition to its logistical advantage (shortening the imaging time)."	( Pharmacologic intervention for the diagnosis of acute cholecystitis: cholecystokinin pretreatment or morphine, or both? Kim, CK, 1997)	1.23
"Morphine, which has a single substituted ammonium group, avidly binds in vitro to antibodies that react with NMBDs."	( Immunoassays in the diagnosis of anaphylaxis to neuromuscular blocking drugs: the value of morphine for the detection of IgE antibodies in allergic subjects. Baldo, BA; Fisher, MM, 2000)	1.25
"Morphine alone has a longer time of onset, with less effect on the pain scores during the 24-hour observation period."	( The use of intra-articular opioids and bupivacaine for analgesia following temporomandibular joint arthroscopy: a prospective, randomized trial. Furst, IM; Kryshtalskyj, B; Weinberg, S, 2001)	1.03
"Morphine has a unique metabolism via glucuronidation (UGT2B7), which results in an active metabolite (morphine-6-glucuronide)."	( Morphine in cancer pain management: a practical guide. Davis, MP; Donnelly, S; Naughton, M; Walsh, D, 2002)	2.48
"A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon."	( [Morphine analgesia: neurobiologic data]. Besson, JM; Le Bars, D; Oliveras, JL, 1978)	1.68
"Morphine has a good arresting effect in attacks of cardiac asthma and corrects or reduces the respiratory alkalosis typical of the disease but at the same time reduces the saturation of blood with oxygen."	( [Acid-base state and blood oxygenation in cardiac insufficiency treated by drug agents]. Inzel', TN; Markov, VA; Shteingardt, IuN, 1978)	0.98
"Morphine probably has a direct effect on cholinergic neurons rather than modifying acetylcholine indirectly through catecholamine neurons."	( Effect of hydroxydopamine on the morphine-induced reduction in brain acetylcholine turnover. Slater, P, 1979)	1.26
"Morphine has a significant protective effect on ethanol-induced gastric lesions. "	( Protective effect of morphine on ethanol-induced gastric lesions in rats: are ATP-dependent potassium channels involved? Bhounsule, SA; Dhume, VG; Diniz D'Souza, RS, )	1.89
"The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL."	( Morphine and etorphine: XIV. Detection by ELISA in equine urine. Blake, J; Green, M; Henry, P; Jeganathan, A; Stanley, S; Tai, HH; Turner, S; Watt, D; Wood, T; Woods, WE, )	2.05
"Morphine has a dose-dependent biphasic effect on colonic myoelectric and contractile activity and alters colonic motility patterns by inhibiting migrating contractions and clusters of contractions."	( Effects of morphine on colonic myoelectric and motor activity in subhuman primates. Condon, RE; Cowles, V; Frantzides, CT; Schulte, WJ, 1990)	1.39
"Morphine has analgesic effects in both phases of the rat formalin test."	( The regulatory role of nitric oxide in morphine-induced analgesia in the descending path of pain from the dorsal hippocampus to the dorsolateral periaqueductal gray. Hashemi, M; Karami, M; Zarrindast, M, 2022)	1.71
"Morphine has no additive effect and there is insufficient evidence on epinephrine and clonidine."	( The Efficacy and Safety of Periarticular Injection in Total Joint Arthroplasty: A Direct Meta-Analysis. Casambre, FD; Della Valle, CJ; Fillingham, YA; Hamilton, WG; Hannon, CP; Kamath, AF; Karas, V; Nelson, N; Spangehl, MJ; Verity, TJ, 2022)	1.44
"Morphine has pharmacological properties that make it particularly difficult to assess the causality of morphine administration with a patient's death, such as its slow transfer between plasma and central nervous sites of action and the existence of the active metabolite morphine-6-glucuronide with opioid agonistic effects, Furthermore, there is no well-defined toxic dose or plasma/blood concentration for morphine."	( Pharmacological data science perspective on fatal incidents of morphine treatment. Dudziak, R; Kringel, D; Lötsch, J; Noufal, Y; Toennes, SW, 2023)	1.87
"Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. "	( The Dopaminergic System in the Ventral Tegmental Area Contributes to Morphine Analgesia and Tolerance. Gao, F; Li, Z; Tu, Y; Wang, J, 2023)	2.59
"Morphine addiction has been associated with astrocytic connexin 43 (Cx43), which plays a role in synaptic homeostasis."	( Maladaptive plasticity induced by morphine is mediated by hippocampal astrocytic Connexin-43. Darvishmolla, M; Heysieattalab, S; Hosseinmardi, N; Janahmadi, M; Saeedi, N; Tavassoli, Z, 2023)	1.91
"Morphine, for example, has shown a dysbiotic effect on the bacterial microbiota in addition to inducing an increase in intestinal permeability facilitating bacterial translocation."	( Opioid system influences gut-brain axis: Dysbiosis and related alterations. Cardona, D; Cruz, F; Hone, AJ; Molina-Torres, G; Roman, P; Rueda-Ruzafa, L; Sánchez-Labraca, N, 2020)	1.28
"Morphine has a phenolic and an alcoholic OH group, while codeine bears only an alcoholic OH group. "	( Using gas-phase chloride attachment for selective detection of morphine in a morphine/codeine mixture by ion mobility spectrometry. Ilbeigi, V; Valadbeigi, Y, 2021)	2.3
"Morphine has been widely used for pain relief, but chronic administration of morphine causes analgesic tolerance, hyperalgesia, and addiction, all of which limit its clinical usage."	( Molecular Mechanism of Neuroprotective Effect of Melatonin on Morphine Addiction and Analgesic Tolerance: an Update. Jiao, L; Liu, Q; Su, LY; Yao, YG, 2021)	1.58
"Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. "	( Morphine Withdrawal Increases Brain-Derived Neurotrophic Factor Precursor. Bachis, A; Campbell, LA; Jenkins, K; Mocchetti, I; Wenzel, E, 2017)	3.34
"Morphine has shown both tumor growth-promoting and growth-inhibiting effects in many published research studies."	( Morphine: double-faced roles in the regulation of tumor development. Chu, HC; Dai, Z; Liang, YX; Yan, Y; Zhang, XY, 2018)	2.64
"Morphine has unwanted hemodynamic and respiratory side effects."	( Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants: a study protocol for a randomized controlled trial. Bogers, AJJC; Jansen, NJG; Kneyber, MCJ; Koomen, E; Maebe, S; Tibboel, D; van den Berghe, G; van Dijk, M; van Rosmalen, J; Vlasselaers, D; Wildschut, ED; Zeilmaker-Roest, GA, 2018)	1.58
"Morphine has large pharmacokinetic variability, which is further complicated by developmental changes in neonates and small infants. "	( PBPK Model of Morphine Incorporating Developmental Changes in Hepatic OCT1 and UGT2B7 Proteins to Explain the Variability in Clearances in Neonates and Small Infants. Emoto, C; Fukuda, T; Hahn, D; Johnson, TN; Neuhoff, S; Vinks, AA, 2018)	2.28
"Morphine has potent pro-dopamine effects that can be manifested as hyper-locomotion and these behavioral effects can undergo conditioning and sensitization. "	( Reversal of morphine conditioned behavior by an anti-dopaminergic post-trial drug treatment during re-consolidation. Carey, RJ; Carrera, MP; de Mello Bastos, JM; Leite Junior, JB; Samuels, RI, 2019)	2.34
"Morphine has been used in the treatment of pain for centuries. "	( Morphine as a treatment of cancer-induced pain-is it safe? A review of in vivo studies and mechanisms. Brinkman, D; Redmond, HP; Wang, JH, 2018)	3.37
"Morphine has a direct role in the central nervous system to relieve pain, but because of its peripheral functions, morphine also has some side effects, such as nausea, constipation, and addiction (Gupta et al."	( The dual effect of morphine on tumor development. Cui, J; Tuerxun, H, 2019)	1.56
"Morphine has substantial pro-dopamine effects and in rodents, this is expressed in behavior as increased locomotor activation. "	( Morphine administered post-trial can induce potent conditioned morphine effects. Carey, RJ; Carrera, MP; de Mello Bastos, JM; Oliveira, LR; Samuels, RI; Santos, BGD, 2019)	3.4
"Morphine has long been the gold standard in first line treatment, but recent publications conclude that ziconotide has largely proven its efficiency and that adverse effects are controllable."	( Intrathecal therapy for pain in cancer patients. Dupoiron, D, 2019)	1.24
"Morphine has also protective properties, which were observed in low concentrations, for nerve cells and also seem to have the ability to reduce cell death in neural cell lines."	( Effects of low-dose morphine suppress methamphetamine-induced cell death by inhibiting the ROS generation and caspase-3 activity. Amini, K; Tahvilian, R; Zhaleh, H, 2019)	1.56
"Morphine has unfavorable side effects including analgesic tolerance. "	( The Emerging Perspective of Morphine Tolerance: MicroRNAs. Hua, Z; Qiu, Y; Zhang, TJ, 2019)	2.25
"Morphine has been a pivotal therapy in acute heart failure (AHF) for more than a century. "	( Adverse dose-dependent effects of morphine therapy in acute heart failure. Aronson, D; Caspi, O; Halfin, E; Naami, R, 2019)	2.24
"Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. "	( Conditioned aversive memory associated with morphine withdrawal increases brain-derived neurotrophic factor in dentate gyrus and basolateral amygdala. Almela, P; Laorden, ML; Martínez-Laorden, E; Milanés, MV; Navarro-Zaragoza, J, 2020)	2.26
"Morphine has also been shown to induce apoptotic cell death in vitro studies, but its in vivo effect in developing rat brain is unknown."	( Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Bajic, D; Commons, KG; Soriano, SG, 2013)	2.55
"Morphine has been reported to accelerate the progression of chronic kidney disease. "	( Morphine induces albuminuria by compromising podocyte integrity. Chandel, N; Cheng, K; Crosson, JT; Gupta, K; Husain, M; Lan, X; Lederman, R; Malhotra, A; Mathieson, PW; Rai, P; Saleem, MA; Singhal, PC, 2013)	3.28
"Morphine clearance has been successfully scaled from preterm neonates to 3-year-old children on the basis of a bodyweight-based exponential (BDE) function and age younger or older than 10 days. "	( Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model. Dahan, A; Danhof, M; Knibbe, CA; Krekels, EH; Sadhavisvam, S; Tibboel, D; Vinks, AA; Wang, C, 2013)	2.14
"Morphine has been used for many years to relieve pain."	( Oral morphine for cancer pain. Moore, RA; Wee, B; Wiffen, PJ, 2013)	1.63
"Morphine has been shown to induce a re-distribution of a MOR-interacting protein Wntless (WLS, a transport molecule necessary for secretion of neurotrophic Wnt proteins), from cytoplasmic to membrane compartments in rat striatal neurons."	( Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat locus coeruleus neurons. Berrettini, WH; Ebersole, B; Grigson, PS; Jaremko, KM; Jenney, CB; Jin, J; Levenson, R; Reyes, BA; Thompson, NL; Van Bockstaele, EJ, 2014)	2.57
"Morphine has been found to elevate dopamine levels, which indicates a potential therapeutic effect in PD treatment that has not been investigated previously."	( Acute morphine treatments alleviate tremor in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. Hu, X; Huang, B; Li, H; Ma, Y; Rizak, JD; Yan, T; Yang, S, 2014)	1.6
"As morphine has been shown to increase striatal dopamine, whereas 6-MAM has not been studied in this respect, we gave i.v."	( Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by intravenous heroin. Boix, F; Gottås, A; Mørland, J; Vindenes, V; Øiestad, EL, 2014)	1.24
"Morphine has been widely used for the treatment of acute, chronic, and cancer pain and is considered the strongest analgesic in clinical care. "	( [Mechanism of spinal pain transmission and its regulation]. Watanabe, C, 2014)	1.85
"Morphine has been used for several decades in cases of pulmonary oedema due to the anxiolytic and vasodilatory properties of the drug. "	( [Morphine in the treatment of acute pulmonary oedema]. Agewall, S; Ellingsrud, C, 2014)	2.76
"Morphine has a profound role in neurofilament (NF) expression. "	( Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence. Das, S; Pal, A, 2015)	3.3
"Morphine has long been known to affect VTA DA cells via GABAergic interneurons."	( Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal. Aston-Jones, G; Kaufling, J, 2015)	1.14
"Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. "	( Morphine in the treatment of acute pulmonary oedema--Why? Agewall, S; Ellingsrud, C, 2016)	3.32
"Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS."	( Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis. Aldrovani, M; Crivelaro, RM; Kobashigawa, KK; Laus, JL; Mineo, TW; Ortencio, KP; Renzo, R; Ribeiro, AP; Silva, GA; Sobrinho B, AA, )	1.96
"Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain."	( A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study. Dirksen, CD; Franssen, FM; Janssen, DJ; Schols, JM; van den Beuken-van Everdingen, MH; Verberkt, CA; Wouters, EF, 2016)	1.38
"Morphine has been used for many years to relieve pain."	( Oral morphine for cancer pain. Moore, RA; Wee, B; Wiffen, PJ, 2016)	1.67
"Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. "	( Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats. He, S; Hu, J; Jiang, L; Zhang, L; Zhang, Y, 2016)	2.14
"Oral morphine has been proposed as an effective and safe alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose."	( Oral morphine dosing predictions based on single dose in healthy children undergoing surgery. Aleksa, K; Anderson, BJ; Brand, KA; Carleton, BC; Cooke, EM; Dawes, JM; Hannam, JA; Jimenez-Mendez, R; Koren, G; Lauder, GR; Montgomery, CJ; Rieder, MJ; Winton, P, 2017)	1.48
"Morphine has been used for several decades in cases of acute pulmonary edema (APE) due to the anxiolytic and vasodilatory properties of the drug. "	( Study Design and Rationale of "A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus MOrphine in Acute Pulmonary Edema": MIMO Trial. Abreu-Gonzalez, P; Aldea-Perona, A; Burillo-Putze, G; Dominguez-Rodriguez, A; Garcia-Saiz, MDM; Harmand, MG; Mirò, O, 2017)	2.11
"Morphine chloride has an inhibitory effect on the contractility of rabbit small intestine in vitro or in vivo. "	( [Effect of morphine chloride on contractility of small intestinal muscle in vitro or in vivo and its mechanisms]. Feng, ZY; Lu, Y; Mao, LG, 2008)	2.18
"Morphine has been used for pain treatment with a long history. "	( Prolonged morphine application modulates Bax and Hsp70 levels in primary rat neurons. Chen, Q; Cui, J; Yu, LC; Zhang, Y, 2008)	2.19
"Morphine withdrawal has a manifest harm in hippocampal CA1 region of rat."	( [The expression of BDNF and PSD-95 in hippocampal CA1 region of morphine-withdrawn rat with different dependent times]. Chen, GD; Chen, P; Han, JG; Liu, XN; Luo, LM; Wang, CB; Zhu, H, 2008)	1.31
"Morphine addiction has become a long-time, serious medical and social problem. "	( Chronic morphine application is protective against cell death in primary human neurons. Chen, Q; Cui, J; Yu, LC; Zhang, Y, 2008)	2.22
"Morphine has demonstrated efficacy in the treatment of acute postoperative pain, yet codeine phosphate is commonly preferred as the standard treatment."	( Morphine infusions after pediatric cranial surgery: a retrospective analysis of safety and efficacy. Bowen-Roberts, T; Hammond, AM; Kent, SK; Ou, CH; Steinbok, P; Warren, DT, 2008)	2.51
"Morphine, which has been previously shown to be unable to desensitize or internalize deltaOR, also behaved as TIPP in failure to utilize Src to regulate deltaOR signaling."	( Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization. Chen, J; Chi, ZQ; Hong, MH; Ji, JL; Liu, JG; Tao, YM; Wang, YJ; Xie, X; Xu, C; Xu, XJ, 2009)	1.07
"Morphine has been widely used for pain management. "	( Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways. Chang, MC; Chen, CA; Cheng, WF; Hsiao, PN; Hsieh, CY; Lin, HW; Sun, WZ, 2009)	3.24
"Morphine has been shown to be an effective intra-articular analgesic, and its anti-inflammatory role seen in this study makes it a potential alternative to bupivacaine."	( The effect of bupivacaine and morphine in a coculture model of diarthrodial joints. Anz, A; Branson, K; Cook, JL; Linville, C; Markway, H; Smith, MJ; Stoker, A, 2009)	1.36
"Like morphine, heroin has high affinity and selectivity for mu-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action."	( Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions. Matulonis, JE; Pan, YX; Pasternak, GW; Rossi, GC; Xu, J; Xu, M, 2009)	1.03
"Morphine has been shown to affect the function of immune system, but the precise mechanism remains to be elucidated. "	( Morphine induces DNA damage and P53 activation in CD3+ T cells. Fukuda, K; Mizota, T; Shoda, T; Tsujikawa, H, 2009)	3.24
"Morphine has been used in a series of experiments in the baboon to characterize developmental changes in fetal glucuronidation."	( Molecular cloning of the baboon UDP-glucuronosyltransferase 2B gene family and their activity in conjugating morphine. Abildskov, K; Garland, M; Weldy, P, 2010)	1.29
"Morphine has been shown to alter gene expression of the major histocompatibility complex, class II (MHC-II) in circulating rat immunocytes. "	( Morphine suppresses MHC-II expression on circulating B lymphocytes via activation of the HPA. Bayer, BM; Houghtling, RA; Nugent, AL, 2011)	3.25
"Morphine has been predicted to show nonlinear blood-brain barrier transport at lower concentrations. "	( Morphine brain pharmacokinetics at very low concentrations studied with accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry. Forsgard, N; Hammarlund-Udenaes, M; Possnert, G; Sadiq, MW; Salehpour, M, 2011)	3.25
"Morphine has well-established antiinflammatory properties and likely attenuates the postburn inflammatory response more than fentanyl, resulting in lower body temperatures."	( Do fentanyl and morphine influence body temperature after severe burn injury? Beers, RJ; Kahn, SA; Lentz, CW, )	1.2
"Morphine has a negative effect on Th cell balance induced by PMA and ionomycin, the mechanism is related to T-bet and GATA3."	( Morphine, but not ketamine, decreases the ratio of Th1/Th2 in CD4-positive cells through T-bet and GATA3. Gao, M; Jin, W; Qian, Y; Sun, J, 2012)	2.54
"  Morphine has high interindividual variability in its analgesic response and side effects profile. "	( Is ethnicity associated with morphine's side effects in children? Morphine pharmacokinetics, analgesic response, and side effects in children having tonsillectomy. Anderson, GD; Farin, FM; Jimenez, N; Lynn, AM; Nielsen, SS; Seidel, K; Shen, DD, 2012)	1.39
"Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. "	( Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels. Angel, TE; Brown, JN; Chan, EY; Clauss, TR; Gritsenko, M; Jacobs, JM; Katze, MG; Larsen, K; McCune, JM; Murnane, RD; Ortiz, GM; Palermo, RE; Purdy, DE; Shukla, AK; Smith, RD, 2012)	3.26
"Morphine has become the preferred drug for analgesia. "	( Preventive and therapeutic effects of penehyclidine hydrochloride on morphine-induced increased bladder pressure, urinary bladder sphincter pressure and histological damage in rabbits. Cui, XG; Li, WZ; Pan, P; Shi, WD; Wang, WW; Zhang, B, 2012)	2.06
"Morphine has been considered the gold standard for treating moderate-to-severe pain, although many new opioid products and formulations have been marketed in the last two decades and should be considered when examining opioid consumption. "	( Using a morphine equivalence metric to quantify opioid consumption: examining the capacity to provide effective treatment of debilitating pain at the global, regional, and country levels. Cleary, JF; Gilson, AM; Maurer, MA; Rathouz, PJ; Ryan, KM, 2013)	2.27
"Morphine has long been used to relieve symptoms in acute failure, but there is little evidence about this potentially useful palliative therapy in CHF."	( Morphine for the relief of breathlessness in patients with chronic heart failure--a pilot study. Dargie, HJ; Harkness, A; Johnson, MJ; McDonagh, TA; McKay, SE, 2002)	2.48
"Morphine has been reported to alter immune function. "	( Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection. Malik, AA; Radhakrishnan, N; Reddy, K; Singhal, PC; Smith, AD, 2002)	3.2
"Morphine has been used to relieve pain for many years. "	( Oral morphine for cancer pain. Barden, J; Edwards, JE; McQuay, HJ; Wiffen, PJ, 2003)	2.28
"Morphine consumption has been increasing each year in many countries including Japan based on the understanding of the WHO report on the treatment of cancer pain."	( [Consumption of morphine preparations in Toyama Medical and Pharmaceutical University Hospital]. Adachi, I; Kawakami, J; Kawashiri, N; Mimura, Y; Nagata, Y; Yamanouchi, T, 2004)	1.39
"1. Morphine has been shown to slow the renal excretion of other drugs. "	( Effects of morphine on methotrexate disposition in mice. Hurwitz, A; Li, Y; Looney, GA, 2004)	1.33
"Morphine sulfate has long been used for analgesia, but clinical applications can be limited by side effects, tolerance, and potential for addiction at therapeutic doses. "	( Intrathecal gabapentin enhances the analgesic effects of subtherapeutic dose morphine in a rat experimental pancreatitis model. Lu, Y; Smiley, MM; Vera-Portocarrero, LP; Westlund, KN; Zidan, A, 2004)	2
"Morphine has cardioprotective effects against ischemic-reperfusion injuries. "	( Morphine mimics the antiapoptotic effect of preconditioning via an Ins(1,4,5)P3 signaling pathway in rat ventricular myocytes. Barrère-Lemaire, S; Combes, N; Nargeot, J; Piot, C; Richard, S; Sportouch-Dukhan, C, 2005)	3.21
"Morphine has long been the gold standard in the control of cancer pain."	( Morphine use for at-home cancer patients in Japan. Kotani, K, 2004)	2.49
"Morphine has been used as a potent analgesic, having a high propensity to induce tolerance and physical dependence following their repeated administration. "	( Proteomic analysis of phosphotyrosyl proteins in morphine-dependent rat brains. Chudapongse, N; Ho, IK; Kim, SY; Lee, SM; Levin, MC; Oh, JT; Park, HJ, 2005)	2.03
"Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. "	( Mast cells are responsible for the lack of anti-inflammatory effects of morphine in CBA mice. Plytycz, B; Stankiewicz, E; Wypasek, E, 2004)	2
"Morphine has been found in cancer cell lines originating from human and animal cells. "	( Human gliomas contain morphine. Olsen, P; Rasmussen, M; Stefano, GB; Tonnesen, E; Zhu, W, 2005)	2.09
"Morphine has been widely accepted as the opioid agonist that sustains signaling because it does not cause receptor desensitization or internalization. "	( Morphine-Induced mu-opioid receptor desensitization. Dang, VC; Williams, JT, 2005)	3.21
"Morphine has been an optimal choice for cancer pain management. "	( Immunosuppression by morphine-induced lymphocyte apoptosis: is it a real issue? Itoh, T; Ohara, T; Takahashi, M, 2005)	2.09
"(3) Morphine has no such effects."	( Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Ahrens, J; Dengler, R; Foadi, N; Haeseler, G; Hecker, H; Leuwer, M, 2006)	1.08
"Morphine has been used widely on the treatment of many types of chronic pain. "	( Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine. Ho, IK; Jang, S; Jeong, MW; Kim, D; Kim, H; Kim, S; Ma, T; Oh, S, 2006)	2.13
"Morphine has been reported to suppress human immune response. "	( Effects of morphine, fentanyl and tramadol on human immune response. Gao, F; Liu, Z; Tian, Y, 2006)	2.17
"Morphine has been shown to alter several behavioural processes. "	( Effects of intracerebroventricularly-injected morphine on anxiety, memory retrieval and locomotor activity in rats: involvement of vasopressinergic system and nitric oxide pathway. Gulec, G; Kahveci, N; Ozluk, K, 2006)	2.03
"Morphine has shown efficacy and tolerability."	( [Morphine maintenance treatment in opiate dependent patients]. Casas Brugué, M; Castells Cervelló, X; Roncero Alonso, C; Sáez Francàs, N, 2007)	1.97
"Morphine has been used for many years to relieve pain."	( Oral morphine for cancer pain. McQuay, HJ; Wiffen, PJ, 2007)	1.57
"Morphine tablets have been formulated to produce an easily ingested effervescent solution when placed in water. "	( Effervescent morphine results in faster relief of breakthrough pain in patients compared to immediate release morphine sulfate tablet. Braun, D; Freye, E; Levy, JV, 2007)	2.15
"Morphine has been contraindicated for pain treatment in acute pancreatitis because of its presumed opioid-induced sphincter of Oddi dysfunction. "	( Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain. de Madaria, E; Horga, JF; Llorens, P; Martínez, E; Martínez, J; Peiró, AM; Pérez-Mateo, M, 2008)	2.05
"Morphine has traditionally been the drug of choice for managing chest pain in acute coronary syndrome (ACS) due to its high analgesic potency, though its physiological effects are poorly understood."	( [Is morphine still the analgesic of choice in acute myocardial infarction?]. Bascuñana, P; Domínguez, B; Gancedo, V; Hernández, A; Rochera, MI; Sola, MA, 2008)	1.63
"Morphine has received intensive research interest for a long time. "	( Morphine: a protective or destructive role in neurons? Chen, Q; Yu, LC; Zhang, Y, 2008)	3.23
"Morphine has been shown to protect the myocardium against ischemia-reperfusion injury through inhibition of glycogen synthase kinase-3beta (GSK-3beta). "	( Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3 beta, SB216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via inhibition of the mitochondrial permeability transition pore. Assaly, R; Berdeaux, A; Dubois-Randé, JL; Morin, D; Obame, FN; Plin-Mercier, C; Zini, R, 2008)	2.09
"Morphine has been universally assumed to act solely on opiate receptors, and predominantly on mu receptors. "	( The role of dopaminergic mechanisms in mediating the central behavioral effects of morphine in rodents. Feigenbaum, J; Yanai, J, 1984)	1.94
"Morphine has been determined in serum, cerebrospinal fluid (c.s.f.) and in five brain regions in the rat after a single intravenous dose, using high performance liquid chromatography with an electrochemical detector. "	( Morphine concentrations in serum, brain and cerebrospinal fluid in the rat after intravenous administration of a single dose. Bolander, H; Kourtopoulos, H; Lundberg, S; Persson, SA, 1983)	3.15
"As morphine has a vasopressin releasing and a brain L-asparaginase inhibiting effect the antidiuretic action of morphine was considered to be linked to its inhibitory effect on the brain L-asparaginase."	( Vasopressin release by D-aspartic acid, morphine and prolyl-leucyl-glycinamide (PLG) in DI Brattleboro rats. Berkman, K; Hatipoğlu, I; Koyuncuoğlu, H; Sabuncu, H, 1984)	1.05
"Morphine has very little effect on the metabolism of DA and NA in the spinal cord."	( Mass fragmentographic analysis of monoamine metabolites in the spinal cord of rat after the administration of morphine. Commissiong, JW, 1983)	1.2
"Morphine has been found in cow and human milk at concentrations of 200 to 500 nanograms per liter. "	( Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (mu) receptors? Brent, DA; Chang, KJ; Cuatrecasas, P; Findlay, JW; Hazum, E; Sabatka, JJ, 1981)	3.15
"Morphine has a variety of actions on the release of pituitary hormones in addition to its analgesic actions. "	( Different receptors mediate morphine-induced prolactin and growth hormone release. Kourides, IA; Pasternak, GW; Spiegel, K, )	1.87
"Morphine (M) treatment has been shown to suppress LH release in rats. "	( Effects of intraventricular administration of catecholamines on luteinizing hormone release in morphine-treated rats. Gallo, RV; Kalra, SP, 1983)	1.93
"Morphine has both excitatory and disruptive effects on MMC cycling, while motilin has only excitatory effects."	( Morphine versus motilin in the initiation of migrating myoelectric complexes. Condon, RE; Cowles, V; Sarna, S, 1983)	2.43
"Morphine has no effect at all on behavioral performance of the unconditioned reflex response."	( Selective, naloxone-reversible morphine depression of learned behavioral and hippocampal responses. Mauk, MD; Thompson, RF; Warren, JT, 1982)	1.27
"Morphine, which has been suggested to inhibit stimulus-evoked substance P release from primary afferent terminals, reduced the early phase of the neurogenic oedema response but it also reduced blood pressure."	( Pharmacology of the neurogenic oedema response to electrical stimulation of the saphenous nerve in the rat. Chahl, LA; Morton, CR, 1980)	0.98
"Morphine has paradoxical effects in learning experiments. "	( Morphine-induced taste avoidance is attenuated with multiple conditioning trials. Moroz, I; Parker, LA; Siegel, S, 1995)	3.18
"Morphine has been shown to alter various aspects of the immune response. "	( Proinflammatory effects of morphine in the rat adjuvant arthritis model. Blake, DR; Claxson, AW; Earl, JR; Morris, CJ, 1994)	2.03
"Morphine has a significant protective effect on ethanol-induced gastric lesions. "	( Gastric cytoprotective effect of morphine is probably not mediated by mu-receptors. Bhounsule, SA; D'Souza, RS; Dhume, VG, )	1.86
"Morphine has no immediate effect on KA-induced activity but is able to bring about a long-term inhibition of sensitization to KA, an effect that is reversed by naloxone."	( Morphine modulates excitatory amino acid-induced activity in the mouse spinal cord: short-term effects on N-methyl-D-aspartate (NMDA) and long-term effects on kainic acid. Larson, AA, 1994)	2.45
"Morphine sulfate has previously been shown to produce a dose-dependent decrease in hepatic phagocytosis when administered as 8-, 25- and 75-mg pellets implanted subcutaneously. "	( Hepatic and splenic phagocytosis in female B6C3F1 mice implanted with morphine sulfate pellets. Brown, RD; Fuchs, BA; Harris, LS; Levier, DG; McCay, JA; Munson, AE, 1993)	1.96
"Morphine has been reported to possess immunosuppressive actions in both in vitro as well as in vivo assays of immune function. "	( Morphine-induced alterations in thymocyte subpopulations of B6C3F1 mice. Freier, DO; Fuchs, BA, 1993)	3.17
"Morphine has been extensively used in the treatment of pulmonary edema, and its action is believed to be mediated in part by its ability to produce peripheral venodilation. "	( Morphine-induced venodilation in humans. Abiose, A; Blaschke, TF; Grossmann, M; Hoffman, BB; Tangphao, O, 1996)	3.18
"Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to compete for opioid receptor binding."	( Morphine metabolites. Christrup, LL, 1997)	2.19
"Morphine augmentation has a reasonably good, though imperfect, specificity and positive predictive value, that are significantly better than for delayed imaging, in addition to its logistical advantage (shortening the imaging time)."	( Pharmacologic intervention for the diagnosis of acute cholecystitis: cholecystokinin pretreatment or morphine, or both? Kim, CK, 1997)	1.23
"Morphine has been demonstrated to modulate immune function. "	( Morphine induces splenocyte apoptosis and enhanced mRNA expression of cathepsin-B. Franki, N; Gibbons, N; Reddy, K; Sanwal, V; Singhal, PC, 1997)	3.18
"Morphine has been shown to decrease proliferative responses of rat T-lymphocytes via central opioid receptors, however, the specific receptor subtype(s) mediating this effect have not been established. "	( Role of central opioid receptor subtypes in morphine-induced alterations in peripheral lymphocyte activity. Bayer, BM; Mellon, RD, 1998)	2
"Morphine has been the standard opioid in patient-controlled analgesia (PCA). "	( Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia. Pitkänen, M; Rosenberg, P; Seppälä, T; Silvasti, M; Svartling, N, 1998)	2
"Morphine has stimulatory effects on feeding and locomotion that are in part mediated by the mesolimbic dopamine system."	( Individual differences in the feeding and locomotor stimulatory effects of acute and repeated morphine treatments. Sills, TL; Vaccarino, FJ, 1998)	1.24
"Morphine has been proposed as a treatment for breathlessness in patients with severe chronic obstructive pulmonary disease (COPD), but there is uncertainty as to whether or not it is effective. "	( The effect of sustained-release morphine on breathlessness and quality of life in severe chronic obstructive pulmonary disease. Black, PN; Poole, PJ; Veale, AG, 1998)	2.03
"Morphine has been reported to increase extracellular levels of dopamine in the brain of intact rats and to potentiate turning induced by amphetamine in nigrally-lesioned rats. "	( Dissociation of morphine-induced potentiation of turning and striatal dopamine release by amphetamine in the nigrally-lesioned rat. Holtzman, SG; Justice, JB; Kimmel, HL, 1998)	2.09
"The morphine metabolism has been studied in order to elucidate its pharmacological actions as well as its adverse effects."	( [Production of morphinone as a metabolite of morphine and its physiological role]. Toki, S; Yamano, S, 1999)	1.04
"Morphine, which has a single substituted ammonium group, avidly binds in vitro to antibodies that react with NMBDs."	( Immunoassays in the diagnosis of anaphylaxis to neuromuscular blocking drugs: the value of morphine for the detection of IgE antibodies in allergic subjects. Baldo, BA; Fisher, MM, 2000)	1.25
"Morphine has long been known to have potent effects on body temperature. "	( Involvement of NMDA receptors and nitric oxide in the thermoregulatory effect of morphine in mice. Akpolat, M; Dokmeci, D; Dokmeci, I; Dost, T; Karadag, CH; Ulugol, A, 2000)	1.98
"Morphine and codeine have been identified and measured in a human urine matrix using high-field asymmetric waveform ion mobility spectrometry (FAIMS) in a tandem combination with electrospray ionization (ESI) and mass spectrometric (MS) detection. "	( Quantitation of morphine and codeine in human urine using high-filed asymmetric waveform ion mobility spectrometry (FAIMS) with mass spectrometric detection. Barnett, DA; Ells, B; Guevremont, R; McCooeye, MA; Purves, RW, 2001)	2.1
"Morphine has multiple cardiovascular effects, but its action on hydrolysis of endothelin 1 (ET-1) has not been investigated."	( Intravenous morphine reduces plasma endothelin 1 concentration through activation of neutral endopeptidase 24.11 in patients with myocardial infarction. Chang, H; Wang, TL, 2001)	2.13
"Morphine alone has a longer time of onset, with less effect on the pain scores during the 24-hour observation period."	( The use of intra-articular opioids and bupivacaine for analgesia following temporomandibular joint arthroscopy: a prospective, randomized trial. Furst, IM; Kryshtalskyj, B; Weinberg, S, 2001)	1.03
"Morphine has a unique metabolism via glucuronidation (UGT2B7), which results in an active metabolite (morphine-6-glucuronide)."	( Morphine in cancer pain management: a practical guide. Davis, MP; Donnelly, S; Naughton, M; Walsh, D, 2002)	2.48
"Morphine has been shown to affect cell-mediated and humoral immune parameters. "	( Differential morphine tolerance development in the modulation of macrophage cytokine production in mice. Gaspani, L; Limiroli, E; Panerai, AE; Sacerdote, P, 2002)	2.13
"A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon."	( [Morphine analgesia: neurobiologic data]. Besson, JM; Le Bars, D; Oliveras, JL, 1978)	1.68
"Morphine has a good arresting effect in attacks of cardiac asthma and corrects or reduces the respiratory alkalosis typical of the disease but at the same time reduces the saturation of blood with oxygen."	( [Acid-base state and blood oxygenation in cardiac insufficiency treated by drug agents]. Inzel', TN; Markov, VA; Shteingardt, IuN, 1978)	0.98
"Morphine probably has a direct effect on cholinergic neurons rather than modifying acetylcholine indirectly through catecholamine neurons."	( Effect of hydroxydopamine on the morphine-induced reduction in brain acetylcholine turnover. Slater, P, 1979)	1.26
"Morphine has been reported to both lower blood pressure (BP) and cause excitation in some species. "	( Biphasic effects of morphine on cardiovascular system of the cat. Wallenstein, MC, 1979)	2.03
"Morphine has little if any effect on the enhanced stimulation produced by acetylcholine thus indicating that the drug does not act directly upon the ganglion."	( Mechanism of morphine block of electrical activity in ganglia of Auerbach's plexus. Comaty, JE; Ehrenpreis, S; Sato, T; Takagi, K; Takayanagi, I, 1976)	1.35
"This morphine-like compound has biological activity as it inhibits the electrically induced contractions both of the guinea pig ileum and mouse vas deferens but the inhibition is not reversed by naloxone or naltrexone."	( Antibodies as a means of isolating and characterizing biologically active substances: presence of a non-peptide, morphine-like compound in the central nervous system. Gintzler, AR; Levy, A; Spector, S, 1976)	0.92
"Morphine has a significant protective effect on ethanol-induced gastric lesions. "	( Protective effect of morphine on ethanol-induced gastric lesions in rats: are ATP-dependent potassium channels involved? Bhounsule, SA; Dhume, VG; Diniz D'Souza, RS, )	1.89
"Morphine treatment has been shown to suppress several immunologic parameters. "	( Differential effects of morphine and naltrexone on the antibody response in various mouse strains. Adler, MW; Bussiere, JL; Eisenstein, TK; Rogers, TJ, 1992)	2.03
"Morphine tolerance has proven to be accompanied by alterations in the efficiency of many neuronal signals, as well as by an inversion of the noradrenergic signal response of cortical acetylcholine terminals and gamma-aminobutyric acid (GABA) neurons in vivo (decreased acetylcholine and increased GABA release in normal animals, vice versa in tolerant). "	( Alpha-2 adrenoreceptor-mediated decrease in gamma-aminobutyric acid outflow in cortical slices and synaptosomes during morphine tolerance. Beani, L; Bianchi, C; Ferraro, L; Morari, M; Simonato, M; Spalluto, G; Tanganelli, S, 1991)	1.93
"Morphine has been considered to be primarily a mu opiate receptor agonist. "	( Delta receptor involvement in morphine suppression of noxiously evoked activity of spinal WDR neurons in cats. Collins, JG; Kitahata, LM; Nakatani, K; Omote, K, 1991)	2.01
"The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL."	( Morphine and etorphine: XIV. Detection by ELISA in equine urine. Blake, J; Green, M; Henry, P; Jeganathan, A; Stanley, S; Tai, HH; Turner, S; Watt, D; Wood, T; Woods, WE, )	2.05
"Morphine has been widely used in the treatment of acute left ventricular failure and ANP is a recently discovered hormone which possesses unique favourable effects in patients with congestive heart failure when administered exogenously."	( Morphine increases plasma immunoreactive atrial natriuretic peptide levels in humans. Isbir, M; Oğütman, C; Ozben, T; Sadan, G; Trakya, A, 1990)	2.44
"Morphine has a dose-dependent biphasic effect on colonic myoelectric and contractile activity and alters colonic motility patterns by inhibiting migrating contractions and clusters of contractions."	( Effects of morphine on colonic myoelectric and motor activity in subhuman primates. Condon, RE; Cowles, V; Frantzides, CT; Schulte, WJ, 1990)	1.39
"Morphine has been intraperitoneally administered twice daily for seven days into rats."	( Morphine affects prodynorphin gene expression in some areas of rat brain. Ferri, S; Lesa, G; Romualdi, P, 1990)	2.44
"Morphine sulfate has been used in hepatobiliary imaging to cause contraction of the sphincter of Oddi, thereby increasing pressure in the biliary tree. "	( Two false-negative results using morphine sulfate in hepatobiliary imaging. Mack, JM; Slavin, JD; Spencer, RP, 1989)	2
"Morphine has species-characteristic effects on pupillary size The effects of morphine on pupillary size, fluctuations and the light reflex were tested with an infrared video pupillometer in the gallamine-paralyzed cat. "	( Morphine-induced mydriasis and inhibition of pupillary light reflex and fluctuations in the cat. Pickworth, WB; Sharpe, LG, 1985)	3.15
"Both morphine and PGE2 have been shown to depress macrophage functions."	( Enhanced prostaglandin E2 and thromboxane B2 release from resident peritoneal macrophages isolated from morphine-dependent rats. Dzoljic, MR; Elliott, GR; van Batenburg, MJ, 1987)	0.94
"Morphine sulfate has been used by several investigators in the cholescintigraphic diagnosis of acute cholecystitis. "	( Intravenous administration of morphine sulfate in hepatobiliary imaging for acute cholecystitis: a review of clinical efficacy. Greenspan, G; Pretorius, HT; Rimkus, DS; Vasquez, TE, 1988)	2.01
"Morphine has been reported to both stimulate and suppress fetal breathing movements (FBM). "	( Dual action of morphine on fetal breathing movements. Amione, J; Clare, S; Dwyer, G; Szeto, HH; Umans, JG; Zhu, YS, 1988)	2.07
"Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. "	( Morphine effects on gentamicin disposition and toxicity in mice. Ben-Zvi, Z; Garty, M; Hurwitz, A, 1988)	3.16
"Morphine has been shown to produce a significant potentiation of indomethacin-induced gastric lesions in rats. "	( Studies on the possible mechanism of morphine-induced potentiation of the gastroulcerogenic effect of indomethacin in rats. Ageel, AM; Parmar, NS; Tariq, M, 1987)	1.99
"Morphine has been the most frequently used narcotic for epidural analgesia."	( Epidural catheter analgesia for the management of postoperative pain. Cullen, ML; Staren, ED, 1986)	0.99
"Morphine has active metabolic products and the accumulation of these in patients with impaired renal function may lead to a clinically observable prolongation of its effect."	( Pharmacokinetics of morphine in two children before and after liver transplantation. Cory, EP; Park, GR; Shelly, MP, 1986)	1.32

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Morphine did not lower arginine vasopressin or catecholamine levels. Morphine had a much slower onset of action with the peak effect being observed 30 min after dosing. The morphine-induced increase in ADP-ribosylation occurred in both Gi and Go.

Excerpt	Reference	Relevance
"Morphine/heroin may increase oxidative stress in drug-dependent persons. "	( Morphine may have a role in telomere shortening. Darvishi, FZ; Saadat, M, 2022)	3.61
"Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure."	( Opioid-blunted cortisol response to stress is associated with increased negative mood and wanting of social reward. Lamm, C; Massaccesi, C; Müller, D; Nater, UM; Quednow, BB; Silani, G; Willeit, M, 2022)	1.44
"Morphine plays an important role in postoperative analgesia after total knee arthroplasty (TKA). "	( Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study. Cao, L; Gu, W; Guo, X; Li, Y; Wulamu, W; Yushan, N; Zhang, X, 2023)	2.69
"Morphine does not cause significant MOR internalization or downregulation, and can readily induce tolerance."	( DAMGO-induced μ opioid receptor internalization and recycling restore morphine sensitivity in tolerant rat. Chen, R; Huang, M; Jiang, W; Kim, DK; Luo, L; Ma, X; Wang, W; Xu, T, 2020)	1.51
"Morphine promotes neuroinflammation after NOD-like receptor protein 3 (NLRP3) oligomerization in glial cells, but the capacity of other opioids to induce neuroinflammation and its relationship to the development of analgesic tolerance is unknown. "	( Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors. Carranza-Aguilar, CJ; Cruz, SL; González-Espinosa, C; Hernández-Mendoza, A; Mejias-Aponte, C; Morales, M; Rice, KC, 2022)	3.61
"Morphine did not enhance wound healing compared to placebo-treated patients. "	( Topical application of morphine for wound healing and analgesia in patients with oral lichen planus: a randomized, double-blind, placebo-controlled study. Güthoff, C; Schmidt-Westhausen, AM; Schramm, C; Stein, C; Zaslansky, R, 2018)	2.23
"Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells."	( Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis. Chen, J; Chen, Y; Li, L; Qin, Y; Xie, Y; Zhang, X, 2017)	2.62
"Morphine was able to increase total antioxidant capacity of H9c2 cells and to reduce the production of reactive oxygen species, protein carbonylation, and lipid peroxidation."	( Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells. Hejnova, L; Karlovska, I; Novotny, J; Skrabalova, J, 2018)	1.52
"Morphine can cause central nervous system side effects which impair driving skills. "	( In silico (computed) modelling of doses and dosing regimens associated with morphine levels above international legal driving limits. Berry, DJ; Boland, JW; Ferreira, D; Johnson, M, 2018)	2.15
"Morphine promotes cell proliferation, migration, and invasion in vitro and in vivo in mouse models."	( The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target. Chen, DT; Chen, YH; Pan, JH; Xing, W; Yan, Y; Yuan, YF; Zeng, WA, 2019)	1.24
"morphine PCA was lower in the ketorolac group vs control group {0-6 h: 0 (0-0) vs 5 (0-10) mg, P<0.0001; 0-48 h: 10 (0-22.5) vs 48.75 (30-82.5) mg, P<0.0001 [median (inter-quartile range, IQR)]}."	( Local infiltration analgesia for total knee arthroplasty: should ketorolac be added? Andersen, KV; Haraldsted, V; Nikolajsen, L; Odgaard, A; Søballe, K, 2013)	1.11
"I.t. morphine did not inhibit the display of CPA but significantly increased PWL, suppressing hyperalgesia (P<0.05)."	( DAMGO in the central amygdala alleviates the affective dimension of pain in a rat model of inflammatory hyperalgesia. Berman, BM; Lao, L; Li, A; Pan, L; Ren, K; Zhang, M; Zhang, RX, 2013)	0.84
"Morphine did not activate ERK and Dyn-DN administration had no effect on morphine-induced antinociception in saline-pretreated rats. "	( Change in functional selectivity of morphine with the development of antinociceptive tolerance. Bobeck, EN; Ingram, SL; Macey, TA; Morgan, MM; Suchland, KL, 2015)	2.13
"Morphine might increase testicular cell apoptosis and reduce sperm concentration by upregulating the expressions of Bax and Caspase-3 in the rat model of morphine tolerance."	( [Impact of morphine on the reproductivity of male rats]. Li, WY; Liu, QZ; Shang, XJ; Shao, Y, 2014)	2.23
"Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT."	( Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway. Mao, M; Qian, Y; Sun, J, 2016)	2.6
"Morphine was found to produce a longer-lasting analgesic effect in the tail immersion test in the control group than in rats. "	( Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion. Babuska-Roczniak, M; Brodziak-Dopierala, B; Cipora, E; Nowak, PG; Oswiecimska, JM; Roczniak, W, 2016)	2.15
"Morphine can increase the generation of free radicals."	( Protective Effect of Thymoquinone Against Morphine Injuries to Kidneys of Mice. Hoseini, M; Jalili, C; Roshankhah, S; Salahshoor, MR; Shabanizadeh, A; Sohrabi, M, 2017)	1.44
"The morphine-induced increase in ACh release was blocked by nor-BNI but not by naloxone."	( Morphine increases acetylcholine release in the trigeminal nuclear complex. Baghdoyan, HA; Bowman, HR; Lydic, R; Zhu, Z, 2008)	2.27
"Morphine caused an increase in antinociception, with early methylphenidate (5.0 mg/kg) exposure potentiating the effects of 5.0 mg/kg morphine."	( Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and locomotor activity in young adult rats. Chisum, AM; Crawford, CA; Furqan, F; Halladay, LR; Iñiguez, SD; Previte, MC, 2009)	1.37
"Morphine caused an increase in FBF at doses of 30 microg min(-1)[3.25 (0.26) ml min(-1) 100 ml(-1)][mean (SEM)] doubling at 100 microg min(-1) to 5.23 (0.53) ml min(-1) 100 ml(-1). "	( Morphine is an arteriolar vasodilator in man. Afshari, R; Bateman, DN; Maxwell, SR; Webb, DJ, 2009)	3.24
"Morphine had a slower onset of action than ROPI, but a stronger analgesic effect of longer duration."	( Effects of intraarticular ropivacaine and morphine on lipopolysaccharide-induced synovitis in horses. de Moraes, AN; Saito, ME; Santos, LC, 2009)	1.34
"The morphine had a lower level of MDA and higher levels of SOD and HSP27 than those in I/R."	( [Preconditioning of morphine protects rabbit myocardium from ischemia-reperfusion injury]. CHANG, YT; LU, XH; RAN, K; XU, JM, 2009)	1.16
"The morphine-induced increase in OA-sensitive PP activity was dependent on the dose and attenuated by the concurrent administration of naloxone (1 mg/kg)."	( Increment of activated serine/threonine protein phosphatase in brain membrane fraction synchronized with antinociceptive effect of morphine in mice. Kiguchi, N; Kishioka, S; Kobayashi, Y; Maeda, T; Ozaki, M, 2010)	1.05
"morphine is known to inhibit cholinergic contractions of the guinea pig small intestine. "	( Unexpected insensitivity of the cholinergic motor responses to morphine in the human small intestine. Bartho, L; Benko, R; Cseke, L; Dékány, A; Illényi, L; Kelemen, D; Molnár, Z; Nemes, D; Papp, A; Varga, G, 2010)	2.04
"Morphine could increase the activity of 5α-redutase, the enzyme that converts testosterone into its respective 5α-redutase derivative dihydrotestosterone (DHT)."	( Could the endogenous opioid, morphine, prevent neural stem cell proliferation? Sharif, S; Shoae-Hassani, A; Tabatabaei, SA; Verdi, J, 2011)	1.38
"Morphine was found to inhibit LPS-induced TNF-α but not CCL2 release in the peritoneal cavity. "	( Morphine decreases early peritoneal innate immunity responses in Swiss-Webster and C57BL6/J mice through the inhibition of mast cell TNF-α release. Cruz, SL; Gonzalez-Espinosa, C; Madera-Salcedo, IK, 2011)	3.25
"Morphine can inhibit metabolism and reduce the oxygen consumption."	( [Protection against acute hypoxic/reoxygenation injury to kidney for rabbit with morphine hypoxic preconditioning by observing the expression of caspase-3 protein]. Huang, W; Jiang, X; Li, H; Luo, J; Ni, J; Wang, Y; Yang, P, 2011)	1.32
"Morphine-induced SCS increase was prevented by NLX, but not MEC."	( Pharmacological relationship between nicotinic and opioid systems in analgesia and corticosterone elevation. Kiguchi, N; Kishioka, S; Kobayashi, Y; Maeda, T; Ueno, K; Yamamoto, A; Yamamoto, C, 2011)	1.09
"Morphine at lower doses (0.5, 1, and 3 mg/kg) increased and, at higher doses (15, 30, and 75 mg/kg), decreased the seizure threshold. "	( The role of alpha2-adrenoceptors in the modulatory effects of morphine on seizure susceptibility in mice. Dehpour, AR; Homayoun, H; Khavandgar, S, 2002)	2
"Morphine is known to inhibit nocturnal uterine contractions in several animal models, and oxytocin is known to be a primary causative factor of uterine contractions. "	( Tocolytic Effect of Morphine via Increased Metabolic Clearance of Oxytocin in the Baboon. Bai, YH; Choi, BC; Pak, SC; Wilson, L, 2002)	2.08
"Morphine use was lower in the femoral group than in the intra-articular group (P <.001)."	( Femoral block provides superior analgesia compared with intra-articular ropivacaine after anterior cruciate ligament reconstruction. Benard, A; Cochard, G; Iskandar, H; Manaud, B; Ruel-Raymond, J, )	0.85
"morphine and fentanyl cause variable degrees of urinary retention."	( Urodynamic changes following intrathecal administration of morphine and fentanyl to dogs. Abu el-Nasr, LM; el-Bindary, EM, )	1.1
"Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490 ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range, 18-3995 ng/mL) (P =.04)."	( A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. Badner, J; Boyett, JM; Cheng, C; Cook, E; Das, S; Innocenti, F; Pantle-Fisher, FH; Pei, D; Ramírez, J; Ratain, MJ; Sawyer, MB; Wright, C, 2003)	1.26
"Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine."	( Effect of morphine and M-cholinoceptor blocking drugs on human sphincter of Oddi during choledochofiberscopy manometry. Jin, JZ; Kong, J; Wang, W; Wu, SD; Zhang, Q, 2003)	1.44
"Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect."	( Sex and estrus cycle differences in the modulatory effects of morphine on seizure susceptibility in mice. Dehghani, M; Dehpour, AR; Gaskari, SA; Homayoun, H; Honar, H; Rashidi, N; Riazi, K; Sadeghipour, H, 2004)	1.29
"Morphine did not produce overestimation of time as assessed by the production or categorization of IRTs."	( The effects of morphine on the production and discrimination of interresponse times. Odum, AL; Ward, RD, 2004)	1.4
"Morphine use was lower in the celecoxib group at all postoperative time-intervals."	( The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion. Ekman, EF; Reuben, SS, 2005)	1.05
"Morphine at lower doses (1-3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threshold."	( The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha 2-adrenoceptors. Dehpour, AR; Ebrahimkhani, MR; Ghaffari, K; Homayoun, H; Honar, H; Jannati, A; Kiani, S; Noorian, AR; Rashidi, N; Riazi, K, 2005)	1.3
"Morphine at lower doses than that used for antinociceptive assay produced both retching and vomiting, whereas fentanyl failed to produce the retching and vomiting in ferrets."	( Effect of a selective GABA(B) receptor agonist baclofen on the mu-opioid receptor agonist-induced antinociceptive, emetic and rewarding effects. Imai, S; Khotib, J; Nakamura, A; Narita, M; Nurrochmad, A; Ozaki, M; Shibasaki, M; Suzuki, T; Yajima, Y, 2005)	1.05
"Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotatio"	( Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. Hefferan, MP; Kakinohana, O; Marsala, J; Marsala, M; Nakamura, S; Tomori, Z, 2005)	1.27
"IA morphine 5 mg does not produce clinically significant pain relief in patients with moderate or severe pain after knee arthroscopy."	( Intra-articular morphine 5 mg after knee arthroscopy does not produce significant pain relief when administered to patients with moderate to severe pain via an intra-articular catheter. Rosseland, LA; Solheim, N; Stubhaug, A, )	1.1
"Morphine failed to cause tolerance in beta2-AR knockout mice."	( The beta2 adrenergic receptor regulates morphine tolerance and physical dependence. Clark, JD; Li, J; Li, X; Liang, DY; Shi, X, 2007)	1.33
"The morphine-induced increase in DBI mRNA expression and its content were completely inhibited by naloxone and beta-FNA, and the inhibitory potential of naloxonazine was about half that of beta-FNA."	( Increase in diazepam binding inhibitor expression by sustained morphine exposure is mediated via mu-opioid receptors in primary cultures of mouse cerebral cortical neurons. Honda, T; Katsura, M; Ohkuma, S; Shibasaki, M; Sumimoto, A; Torigoe, F; Tsujimura, A, 2007)	1.06
"Morphine produces an increase in DA release in the brain, which may provide positive reinforcement contributing to the development of motivational aspects of drug-seeking and maintenance behavior."	( Potential roles of GABA receptors in morphine self-administration in rats. Choi, KH; Jang, EY; Kim, HS; Kim, JA; Kim, MR; Lee, BH; Shim, I; Yang, CH; Yoon, SS; Yun, J, 2007)	1.33
"Morphine can inhibit inflammatory edema in experimental animals. "	( Intrathecally injected morphine inhibits inflammatory paw edema: the involvement of nitric oxide and cyclic-guanosine monophosphate. Brock, SC; Tonussi, CR, 2008)	2.1
"The morphine induced increase of striatal DOPAC (3,4-dihydroxyphenylacetic acid) content was also inhibited by ACTH treatment, however, neither the analgesia, nor the hypermotility caused by morphine were affected."	( Loss of sensitivity to morphine induced by prolonged ACTH treatment. Fekete, MI; Kanyicska, B; Stark, E; Szentendrei, T, 1984)	1.06
"Morphine alone did not cause an increase in the number of jumping mice, but increased the reaction time which reached a maximum 1 h after administration and gradually returned to the control level after 6 h."	( Alterations by captopril of pain reactions due to thermal stimulation of the mouse foot: interactions with morphine, naloxone and aprotinin. Ercan, ZS; Ilhan, M; Türker, RK, 1980)	1.2
"Morphine-induced increase of dopamine metabolism in the striatum and nucleus accumbens was studied in rats treated with parachlorophenylalanine, an inhibitor of serotonin synthesis, or metergoline and mianserin, two serotonin antagonists. "	( Evidence of serotonin involvement in the effect of morphine on dopamine metabolism in the rat nucleus accumbens but not in the striatum. Invernizzi, R; Samanin, R; Spampinato, U, 1984)	1.96
"7 Morphine may produce peripheral analgesia by inhibiting adenylatecyclase activity at the nociceptors."	( Peripheral analgesia: mechanism of the analgesic action of aspirin-like drugs and opiate-antagonists. Ferreira, SH, 1980)	0.82
"Morphine was shown to produce the naloxone-removable activation of adenylate cyclase, the relationship between enzymatic activity and opiate concentration in the medium being complex in nature."	( [Effect of morphine on the cAMP level of lymphocytes]. Kost, NV; Zozulia, AA, )	1.24
"The morphine-induced increase in locomotor activity and analgesia was attenuated in PCP (40 mg/kg per day i.p."	( Attenuation of pharmacological effects and increased metabolism of phencyclidine in morphine tolerant mice. Ho, IK; Nabeshima, T; Sivam, SP, 1984)	0.97
"The morphine-induced increase did not require the presence of intact central connections."	( Effects of morphine on superior cervical ganglion and iris of the immature rat. Kirby, ML; Mattio, TG, 1983)	1.14
"Morphine caused an increase in urine flow which was variable in magnitude and duration."	( Antinatriuretic effect of acute morphine administration in conscious rats. Murphy, JC; Walker, LA, 1984)	1.27
"I.m. morphine caused an increase in forehead pain threshold, depression of the carbon dioxide response and some deterioration of cerebral function."	( Experimental comparison of extradural and i.m. morphine. Clark, M; Crawford, M; Liberman, H; Pybus, DA; Torda, TA, 1980)	0.97
"The morphine-produced increase in Type A cells was antagonized by 0.10 mg/kg of naloxone, whereas the suppression of B cells was blocked only by pretreatment with 5.0 mg/kg of naloxone."	( The effects of low doses of morphine on the activity of dopamine-containing cells and on behavior. Caggiula, AR; Hatfield, CB; Ostrowski, NL, )	0.91
"A morphine-induced increase in locomotion was first seen on Day 17 (after 0.5 mg/kg morphine)."	( Ontogenesis of morphine-induced behavior in the rat. Caza, PA; Spear, LP, 1980)	1.17
"Morphine is known to produce mydriasis in mice. "	( Enkephalin mydriasis in mice. Eshel, Y; Keren, O; Korczyn, AD, 1980)	1.7
"Morphine did not inhibit noncholinergic contractions."	( Differential inhibition of cholinergic and noncholinergic neurogenic contractions by mu opioid and alpha-2 adrenergic agonists in guinea pig ileum. Galligan, JJ, 1993)	1.01
"Morphine did not produce any modification in plasma corticosterone at doses of 3 or 10 mg/kg i.p., whereas it produced a significant increase in corticosterone secretion at doses of 20 or 30 mg/kg i.p., 30 min after its administration."	( Involvement of kappa-opioid receptor mechanisms in the calcitonin-induced potentiation of opioid effects at the hypothalamus-pituitary-adrenocortical axis. Martín, MI; Milanés, MV; Vargas, ML, 1994)	1.01
"Only morphine was able to increase the cAMP response to isoproterenol."	( Effects of opioid substances on cAMP response to the beta-adrenergic agonist isoproterenol in human mononuclear leukocytes. Ioverno, A; Lotti, G; Musso, NR; Pende, A; Vergassola, C, 1995)	0.75
"Morphine was found to inhibit sex behavior in a dose dependent way."	( Opioids and sexual behavior in the male rabbit: the role of central and peripheral opioid receptors. Agmo, A; Contreras, JL; Paredes, RG, 1994)	1.01
"The morphine induced increase in blood glucose in the fed rats was abolished by naloxone (p < 0.001)."	( Morphine and morphine/naloxone modification of glucose, glucagon and insulin levels in fasted and fed rats. Burhol, PG; Jensen, T; Johansen, O; Jorde, R; Reikerås, O; Tønnesen, T, 1993)	2.21
"morphine, produce analgesia that can be potentiated by restraint stress."	( Restraint stress potentiates analgesia induced by 5'-N-ethylcarboxamidoadenosine: comparison with morphine. Holtzman, SG; Woolfolk, DR, 1993)	1.22
"morphine did not produce antagonism of the antinociceptive action of this mu opiate, the leftward displacement of the i.c.v."	( Modulation of morphine antinociception by swim-stress in the mouse: involvement of supraspinal opioid delta-2 receptors. Bowen, WD; Hruby, VJ; Mosberg, HI; Porreca, F; Portoghese, PS; Sultana, M; Takemori, AE; Vanderah, TW; Wild, KD, 1993)	1.37
"Morphine prevented the increase of fluorescein uptake, but naloxone failed to antagonize this effect."	( Involvement of opioid receptors in shaking behaviour induced by paraquat in rats. Endo, T; Hara, S; Iwata, N; Kano, S; Kawaguchi, N; Kuriiwa, F, 1993)	1.01
"Morphine did not produce any demonstrable effect on the sympathetic nervous system nor did it provide pain relief for any patient."	( Morphine injected around the stellate ganglion does not modulate the sympathetic nervous system nor does it provide pain relief. Casale, R; Glynn, C, 1993)	2.45
"Morphine did not cause a further suppression of the antibody response in beige mice compared to placebo."	( Effects of in vivo morphine treatment on antibody responses in C57BL/6 bgJ/bgJ (beige) mice. Adler, MW; Bussiere, JL; Eisenstein, TK; Rogers, TJ, 1993)	1.34
"Morphine's potency to inhibit cAMP accumulation is the same before and after chronic treatment, suggesting that the apparent tolerance results from cyclase activation, rather than from receptor desensitization."	( Adenylylcyclase supersensitization in mu-opioid receptor-transfected Chinese hamster ovary cells following chronic opioid treatment. Avidor-Reiss, T; Bayewitch, M; Levy, R; Matus-Leibovitch, N; Nevo, I; Vogel, Z, 1995)	1.01
"morphine to produce antiallodynic effects may be due, in part, to the lack of available functional spinal opioid mu-receptors which may occur following nerve injury."	( Characterization of the antiallodynic efficacy of morphine in a model of neuropathic pain in rats. Bian, D; Lai, J; Nichols, ML; Ossipov, MH; Porreca, F, 1995)	1.27
"The morphine-induced increase in acetylcholine output was suppressed by the blockade of dopamine D1 receptors with SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine) (0.1 mg/kg s.c.), which also suppressed the morphine-induced motor stimulation."	( Chronic morphine increases hippocampal acetylcholine release: possible relevance in drug dependence. Carta, G; Casu, MA; Gessa, GL; Imperato, A; Mascia, MS; Obinu, MC, 1996)	1.21
"The morphine-induced increase in locomotor activity occurred significantly earlier and was greater in the deficient diet group."	( Influence of a dietary alpha-linolenic acid deficiency on learning in the Morris water maze and on the effects of morphine. Bourre, JM; Clément, M; Coudereau, JP; Francès, H; Monier, C; Sandouk, P, 1996)	0.99
"Morphine seems to enhance the accumulation of macromolecules in the mesangium, independent of its action on mesangial cells."	( Morphine modulates mesangial immunoglobulin G uptake in rats with antithymocyte serum-induced mesangial cell injury. Pan, CQ; Sagar, S; Singhal, PC; Stahl, RA; Valderrama, E, 1996)	2.46
"5. Morphine did not inhibit forskolin-stimulated cyclicAMP formation in cultured cells expressing the nociceptin receptor."	( Characterization of nociceptin hyperalgesia and allodynia in conscious mice. Hara, N; Imanishi, T; Ito, S; Minami, T; Mori, H; Okuda-Ashitaka, E; Onaka, M; Sakai, M; Shingu, K; Sugimoto, T, 1997)	0.81
"morphine recorded lower pain scores and required less supplementary analgesia."	( The efficacy of intra-articular morphine for postoperative knee arthroscopy analgesia. Bjorksten, AR; Hart, JA; McCullough, K; Richardson, MD, 1997)	1.3
"The morphine-induced increase in DA oxidative metabolism is highly correlated with that of xanthine."	( Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric acid release in freely moving rats. De Natale, G; Desole, MS; Enrico, P; Esposito, G; Miele, E; Miele, M; Migheli, R; Mura, MA; Serra, P, 1998)	1.1
"morphine 50 microg may produce better postoperative analgesia with fewer side effects than i.t."	( The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean section analgesia. Chin, YJ; Chung, CJ; Kim, JS; Park, HS, 1998)	1.27
"Morphine showed a lower peak percentage maximum possible effect (%MPE) in the colorectal distension test than in the tail flick test."	( Interaction of intrathecally infused morphine and lidocaine in rats (part I): synergistic antinociceptive effects. Kaneko, M; Kirihara, Y; Kosaka, Y; Saito, Y; Sakura, S, 1998)	1.29
"Morphine did not produce a change in subjectively evaluated vigilance and the blood pH."	( [Value of orally administered retard morphine for therapy of severe pulmonary emphysema of the pink-puffer type. A pilot study]. Köhler, D; Schönhofer, B, 1998)	1.29
"Morphine alone did not enhance the generation of TNF-alpha by mesangial cells, however, an enhanced (P < 0.001) TNF-alpha production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. "	( Morphine stimulates mesangial cell TNF-alpha and nitrite production. Gibbons, N; Kapasi, AA; Mattana, J; Singhal, PC, 2000)	3.19
"The morphine-induced increase in SPARC levels in the basolateral amygdala persisted after morphine withdrawal and coincided with the duration of locomotor sensitization."	( Increased sensitivity to the stimulant effects of morphine conferred by anti-adhesive glycoprotein SPARC in amygdala. Ikemoto, M; Imamura, T; Inoue, K; Takita, M, 2000)	1.04
"The morphine-induced increase in dopamine (DA) turnover in the limbic forebrain was suppressed under inflammation, and the suppression was abolished by the pretreatment with nor-BNI."	( Mechanism of opioid dependence and interaction between opioid receptors. Kishimoto, Y; Narita, M; Ozaki, S; Suzuki, T, 2001)	0.79
"Morphine is found to inhibit both ATP-synthetase and ATP-ase activities in mitochondria, but not in submitochondrial particles."	( [Mechanism of opiate of oxidative phosphorylation in mitochondria]. Chistiakov, VV; Gegenava, GP, 1976)	0.98
"The morphine-induced increase in brain 5-HT turnover is likely to be involved in the morphine-induced decrease in locomotor activity and hypothermia in rats."	( Effects of narcotic analgesics on serotonin metabolism in brain of rats and mice. Oka, T; Sawa, A, 1976)	0.74
"morphine caused an increase and AOAA, a decrease."	( Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems. Cott, J; Engel, J, 1977)	1.21
"Morphine induced an increase in the frequency of group formations without disruption of grooming and rearing patterns."	( Behavioral effects of low, acute doses of morphine in nontolerant groups of rats in an open-field test. Hecht, A; Schiørring, E, 1979)	1.25
"Morphine did not produce hypothermia at any dose tested.3 Injection of 10 mug morphine sulphate into the third ventricle produced similar hyperthermias at ambient temperatures (tas) of 4-6, 21-23 and 33-36 degrees C."	( Hyperthermic responses to central and peripheral injections of morphine sulphate in the cat. Clark, WG; Cumby, HR, 1978)	1.22
"of morphine produced an increase in locomotor activity and a concomitant increase in ACh utilization."	( Tolerance development to the biphasic effects of morphine on locomotor activity and brain acetylcholine in the rat. Domino, EF; Vasko, MR, 1978)	1.03
"Antimorphine antibodies inhibit the activity of morphine conjugates of mitochondrial malate dehydrogenase. "	( Mechanism by which antibodies inhibit hapten-malate dehydrogenase conjugates. An enzyme immunoassay for morphine. Huisjen, J; Rowley, GL; Rubenstein, KE; Ullman, EF, 1975)	1.03
"The morphine-induced increase in cAMP content also disappeared after naloxone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Modifications of striatal D2 dopaminergic postsynaptic sensitivity during development of morphine tolerance-dependence in mice. Cebeira, M; Fernández-Ruiz, JJ; Hernández, ML; Navarro, M; Ramos, JA; Rodriguez de Fonseca, F, 1992)	0.99
"The morphine-produced increase in the mechanical withdrawal threshold, however, was shifted rightward in a parallel fashion by intrathecal pretreatment with atropine."	( Tonic cholinergic inhibition of spinal mechanical transmission. Gebhart, GF; Zhuo, M, 1991)	0.76
"Morphine did not inhibit protein synthesis or adenylate cyclase activity in a T cell clone under identical conditions, indicating that MS, in this concentration range, does not simply interfere with all cell functions in a nonspecific manner."	( Effect of high doses of morphine on Con-A induced lymphokine production in vitro. Jessop, JJ; Taplits, MS, )	1.16
"Morphine was shown to enhance dopamine release in the rat olfactory tubercle, nucleus accumbens, prefrontal cortex and pyriform cortex, as assessed by increased 3-methoxytyramine (3-MT) levels and 3-MT accumulation after pargyline treatment. "	( Morphine stimulation of mesolimbic and mesocortical but not nigrostriatal dopamine release in the rat as reflected by changes in 3-methoxytyramine levels. Rao, TS; Wood, PL, 1991)	3.17
"Morphine was found to inhibit human granulocyte aggregation and ATP, thromboxane B2 (TxB2), and leukotriene B4 (LTB4) secretion during cell aggregation. "	( Peptide opioids and morphine effects on inflammatory process. Fioravanti, A; Frigo, GM; Lecchini, S; Marcoli, M; Mazzone, A; Notario, A; Pasotti, D; Ricevuti, G, 1990)	2.05
"Morphine given to cause spasm of the sphincter increased basal pressure and frequency of the phasic waves in all controls."	( Sphincter of Oddi motor activity in patients with anomalous pancreaticobiliary junction. Ikeda, S; Matsumoto, S; Tanaka, M; Yoshimoto, H, 1991)	1
"Morphine was found to increase histamine-induced bronchospasm and to prevent serotonin-induced bronchoconstriction."	( [The effect of morphine and naloxone on histamine- and serotonin-induced bronchospasms]. Karpov, OI, )	1.21
"Both morphine and halothane produce a dose-related inhibition of electrically induced muscle contraction."	( Synergistic interaction of morphine and halothane in the guinea pig ileum: effects of pertussis toxin. Puig, MM; Turndorf, H; Warner, W, 1990)	1.03
"Morphine did not produce a significant effect in femoral arteries."	( Effect of morphine on the cat middle cerebral artery. Lopez-Rico, M; Marin, J; Recio, L; Reviriego, J; Salaices, M, 1986)	1.39
"Morphine caused an increase in the affinity for agonist binding to the D-2-HI site (83-fold increase)."	( Cyclo (Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine. DeLeon-Jones, F; Fields, JZ; Lee, JM; Ritzmann, RF, 1987)	1.22
"The morphine-induced increase in ADP-ribosylation occurred in both Gi and Go, and was observed over a 30-fold range of NAD concentrations used."	( Regulation of G proteins by chronic morphine in the rat locus coeruleus. Duman, RS; Erdos, JJ; Nestler, EJ; Tallman, JF; Terwilliger, R, 1989)	1.03
"Morphine did not increase the mean duration of bupivacaine analgesia significantly, but increased the rate of inadequate pain relief."	( Controlled trial of extradural bupivacaine with fentanyl, morphine or placebo for pain relief in labour. Conseiller, C; Dailland, P; Jacquinot, P; Jasson, J; Jorrot, JC; Lirzin, JD; Talafre, ML, 1989)	1.24
"Morphine was shown to enhance dopamine metabolism, as assessed by increased dihydroxyphenylacetic acid measurements, in the mesocortical dopaminergic projections of the rat (cingulate, pyriform and prefrontal cortices). "	( Reversal of the actions of morphine on mesocortical dopamine metabolism in the rat by the kappa agonist MR-2034: tentative mu-2 opioid control of mesocortical dopaminergic projections. Iyengar, S; Kim, HS; Wood, PL, 1987)	2.01
"Morphine had a much slower onset of action with the peak effect being observed 30 min after dosing."	( kappa-Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat. Hill, RG; Hughes, J; Leighton, GE; Rodriguez, RE, 1988)	1
"The morphine-induced increase in adenylate cyclase required chronic exposure to the opiate, as shorter treatment times, namely 2 hr and 1 day, failed to produce this effect."	( Acute and chronic opiate-regulation of adenylate cyclase in brain: specific effects in locus coeruleus. Duman, RS; Nestler, EJ; Tallman, JF, 1988)	0.76
"Morphine does not cause this excitatory interaction, and is the drug of choice provided an allowance is made for possible potentiation of the depressive narcotic effect."	( Monoamine oxidase inhibitors and narcotic analgesics. A critical review of the implications for treatment. Browne, B; Linter, S, 1987)	0.99
"Morphine did not lower arginine vasopressin or catecholamine levels."	( Morphine inhibits the pituitary-adrenal response to ovine corticotropin-releasing hormone in normal subjects. Chrousos, GP; Cutler, GB; Goldstein, DS; Koppelman, MC; Loriaux, DL; Rittmaster, RS; Sobel, DO, 1985)	2.43
"morphine increase tonic descending inhibitory processes? and 2) what are the effects of i.c.v."	( Intracerebroventricular morphine decreases descending inhibitions acting on lumbar dorsal horn neuronal activities related to pain in the rat. Bouhassira, D; Le Bars, D; Villanueva, L, 1988)	1.3
"Morphine was found to produce a potent analgesia, as measured by latency to retract a hindpaw from a 52 degree C hotplate, in rat pups as young as 1 day of age."	( The ontogeny of opiate tolerance and withdrawal in infant rats. Cramer, CP; Fanselow, MS, 1988)	1
"Morphine was found to produce a temporal course of excessive grooming quite different from that produced by codeine."	( Excessive grooming induced by the administration of codeine and morphine. Brakkee, J; Danks, AM; Gispen, WH; Isaacson, RL; Schefman, K, 1988)	1.23
"5. Morphine failed to activate an aganglionic rectum in a patient with Hirschsprung's disease, indicating that it had no direct effect on smooth muscle cells."	( Effects of morphine on electrical activity of the rectum in man. Bouvier, M; Grimaud, JC; Naudy, B; Salducci, J, 1987)	1.18
"Morphine-induced increase in resistance to passage from the common duct to the intestines in normals is of a magnitude that forces the total amount of bile to accumulate in the gallbladder."	( The effects of morphine on biliary dynamics. A scintigraphic study with 99mTc-HIDA. Kraglund, K; Oster-Jørgensen, E; Pedersen, SA, 1987)	1.35
"morphine and NE can produce effective analgesia with minimal effects on cardiovascular and respiratory function."	( Analgesia and autonomic function following intrathecal administration of morphine and norepinephrine to the rat. Cervenko, FW; Jhamandas, K; Loomis, CW; Milne, B; Sutak, M, 1985)	1.22
"The morphine-induced increase in DOPAC and HVA concentrations in the brain are discussed in the light of the hypothesis that dopamine might participate not only in the extrapyramidal motor system but also in the sensory mechanisms of the brain."	( Effect of morphine on the cerebral contents of metabolites of dopamine in normal and tolerant mice: its possible relation to analgesic action. Fukui, K; Takagi, H, 1972)	1.13
"For morphine, a 33.3% increase at 4°C and a 23.4% increase at RT were observed after 2 weeks, respectively, possibly due to 6-AM degradation, while no changes ≥20% were observed at 37°C."	( Stability of 21 Cocaine, Opioid and Benzodiazepine Drug Analytes in Spiked Meconium at Three Temperatures. Marin, SJ; McMillin, GA; Wu, F, 2017)	0.94

Treatment

Morphine-treated mice had higher energy expenditure and respiratory quotient, indicating a shift toward carbohydrate metabolism. Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment.

Excerpt	Reference	Relevance
"no morphine treatment in AHF patients."	( Intravenous morphine use in acute heart failure increases adverse outcomes: a meta-analysis. Chen, Q; Chen, Y; Dong, S; Lin, Y; Liu, H; Pang, X; Yuan, J, 2021)	1.51
"Morphine treatment also increases gastric acid secretion and causes delays in gastric emptying."	( Opioid Use in Murine Model Results in Severe Gastric Pathology that May Be Attenuated by Proton Pump Inhibition. Ghosh, N; Kesh, K; Ramakrishnan, S; Roy, S, 2022)	1.44
"Morphine-treated mice had higher energy expenditure and respiratory quotient, indicating a shift toward carbohydrate metabolism."	( Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice. Barlow, D; Bouxsein, ML; Brooks, DJ; Carvalho, AL; Farina, NH; Houseknecht, KL; King, T; Langlais, AL; Lian, JB; Morrill, B; Motyl, KJ, 2022)	1.85
"Morphine treatment significantly increased the physical interaction of α2δ-1 with GluN1 and their synaptic trafficking in the NAc."	( α2δ-1 protein drives opioid-induced conditioned reward and synaptic NMDA receptor hyperactivity in the nucleus accumbens. Chen, H; Chen, SR; Jin, D; Pan, HL, 2023)	1.63
"Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment."	( Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in SIV infection. Acharya, A; Buch, S; Byrareddy, SN; Callen, S; Dyavar, SR; Emanuel, K; Eudy, J; Fletcher, CV; Fox, HS; Guda, C; Kubik, G; Lamberty, BG; Morsey, BM; Niu, M; Periyasamy, P, 2022)	2.89
"Morphine treatment counteracted pain, anxio-depressive behaviors and neuroinflammatory activation in both young adult and older adult mice."	( Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine. Amodeo, G; Baciarello, M; Bignami, EG; D'Agnelli, S; Franchi, S; Galimberti, G; Sacerdote, P, 2023)	1.83
"Morphine-treated group was subdivided into seven subgroups for receiving vehicle, normal saline, cinnamaldehyde (1.25, 5, and 20 mg/kg), naloxone, and cinnamaldehyde plus naloxone before morphine."	( Behavioral, histopathological, and biochemical evaluations on the effects of cinnamaldehyde, naloxone, and their combination in morphine-induced cerebellar toxicity. Farshid, AA; Imani, M; Mahmoudi, S; Noroozinia, F; Tamaddonfard, E, 2022)	1.65
"In morphine-treated rats, level of BDNF and p-CREB/CREB ratio reduced during both forms of decision making while p-GSK3β/GSK3β ratio increased during delay-based and did not have a significant difference with the control group during effort-based decision making."	( Naloxone-precipitated withdrawal ameliorates impairment of cost-benefit decision making in morphine-treated rats: Involvement of BDNF, p-GSK3-β, and p-CREB in the amygdala. Fatahi, Z; Haghparast, A; Karimi-Haghighi, S; Khodagholi, F; Moradi, M; Zeinaddini-Meymand, A, 2020)	1.29
"Morphine-treated socially exploring mice developed greater locomotor sensitization than those in morphine-treated socially avoiding mice."	( Response to opioids is dependent on sociability levels. Eitan, S; Madison, CA; Wellman, PJ, 2020)	1.28
"Mean morphine treatment duration was significantly longer with clonidine (34.4 days, SD = 10.6) compared with phenobarbital (25.5 days, SD = 7.3, p = 0.026)."	( Clonidine versus phenobarbital as adjunctive therapy for neonatal abstinence syndrome. Brusseau, C; Burnette, T; Heidel, RE, 2020)	1.01
"Morphine treatment markedly attenuated viability and proliferative ability in HT-22 cells, while apoptotic rate increased. "	( Morphine induces the apoptosis of mouse hippocampal neurons HT-22 through upregulating miR-181-5p. An, XH; Liu, JH; Wang, JW; Wang, YL; Yang, ZY; Zhang, XQ, 2020)	3.44
"The Morphine for Treatment of Dyspnea in Patients With COPD (MORDYC) study was a randomized, double-blind, and placebo-controlled study of a 4-week intervention. "	( Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status: A Randomized Clinical Trial. Hameleers, N; Janssen, DJA; Schols, JMGA; van den Beuken-van Everdingen, MHJ; Verberkt, CA; Wouters, EFM, 2020)	1.41
"Morphine treatment (Mor) reduced fecal outputs starting on"	( An opioid receptor-independent mechanism underlies motility dysfunction and visceral hyperalgesia in opioid-induced bowel dysfunction. Fu, Y; Hegde, S; Huang, LM; Lin, YM; Shi, DW; Shi, XZ; Tang, Y, 2021)	1.34
"Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. "	( Morphine increases myocardial triacylglycerol through regulating adipose triglyceride lipase S406 phosphorylation. Li, D; Li, L; Wang, J; Zhang, H, 2021)	3.51
"Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed."	( Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures. Hagman, R; Hanson, J; Höglund, OV; Lagerstedt, AS; Nonthakotr, C; Olsson, U; Pettersson, A; Srithunyarat, T; Stridsberg, M, 2017)	1.18
"Morphine treatment delayed macrophage infiltration, sonic Hedgehog pathway activation and expression of pdx-1 and ptf-1."	( Morphine worsens the severity and prevents pancreatic regeneration in mouse models of acute pancreatitis. Banerjee, S; Barlass, U; Cheema, H; Dawra, RK; Dixit, A; Dudeja, V; Dutta, R; George, J; Giri, B; Meng, J; Roy, S; Saluja, AK; Sareen, A; Yuan, Z, 2018)	2.64
"Morphine treatment worsens the severity of acute pancreatitis and delays resolution and regeneration. "	( Morphine worsens the severity and prevents pancreatic regeneration in mouse models of acute pancreatitis. Banerjee, S; Barlass, U; Cheema, H; Dawra, RK; Dixit, A; Dudeja, V; Dutta, R; George, J; Giri, B; Meng, J; Roy, S; Saluja, AK; Sareen, A; Yuan, Z, 2018)	3.37
"Morphine treatment and morphine withdrawal increased both BDNF and proBDNF levels."	( Morphine Withdrawal Increases Brain-Derived Neurotrophic Factor Precursor. Bachis, A; Campbell, LA; Jenkins, K; Mocchetti, I; Wenzel, E, 2017)	2.62
"Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend) according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine."	( A comparison of oral controlled-release morphine and oxycodone with transdermal formulations of buprenorphine and fentanyl in the treatment of severe pain in cancer patients. Leppert, W; Nosek, H; Nosek, K; Onichimowski, D; Wordliczek, J, 2017)	1.44
"Morphine treatment resulted in a significant upregulation of β-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III)."	( Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of β-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex. Hejnova, L; Novotny, J; Skrabalova, J, 2017)	1.58
"morphine treatment was used to induce anti-nociceptive tolerance."	( Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia. Dong, J; Huang, M; Jiang, W; Luo, L; Ma, X; Wang, W; Xu, T; Zhang, X, 2018)	1.43
"Morphine treatment decreased expression of pro-inflammatory factors (CCL5, iNOS) and reduced cognitive performance in LP-BM5-infected mice, correlating to increased hippocampal viral load and a blunted type 1 IFN response."	( Morphine-potentiated cognitive deficits correlate to suppressed hippocampal iNOS RNA expression and an absent type 1 interferon response in LP-BM5 murine AIDS. Cao, L; Kumar, S; Leeming, R; McLane, VD; Rau, S; Willis, CL, 2018)	2.64
"Morphine 1.5 and 5 mg treatments led to consistently and significantly elevated PPT and PPtol measures in men, but not in women."	( Effects of intramuscular morphine in men and women with temporomandibular disorder with myofascial pain. Auh, QS; Kang, SK; Lee, YH; Park, H; Ro, JY, 2018)	1.51
"The morphine treatments were administered once per day for 5 days."	( Reversal of morphine conditioned behavior by an anti-dopaminergic post-trial drug treatment during re-consolidation. Carey, RJ; Carrera, MP; de Mello Bastos, JM; Leite Junior, JB; Samuels, RI, 2019)	1.37
"Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001)."	( Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine. Bolognese, L; Cantor, WJ; Cequier, A; Chettibi, M; Collet, JP; Ecollan, P; Goodman, SG; Hamm, CW; Hammett, CJ; Heutz, WMJM; Huber, K; Janzon, M; Lapostolle, F; Lassen, JF; Licour, M; Merkely, B; Montalescot, G; Silvain, J; Stibbe, O; Storey, RF; Ten Berg, J; Tsatsaris, A; Van't Hof, AW; Zeymer, U, 2019)	2.68
"Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. "	( Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine. Bolognese, L; Cantor, WJ; Cequier, A; Chettibi, M; Collet, JP; Ecollan, P; Goodman, SG; Hamm, CW; Hammett, CJ; Heutz, WMJM; Huber, K; Janzon, M; Lapostolle, F; Lassen, JF; Licour, M; Merkely, B; Montalescot, G; Silvain, J; Stibbe, O; Storey, RF; Ten Berg, J; Tsatsaris, A; Van't Hof, AW; Zeymer, U, 2019)	3.4
"Morphine treatment beginning at the time of injury impairs nociceptive recovery and other outcomes. "	( Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice. Clark, JD; Guo, TZ; Irvine, KA; Kingery, WS; Li, WW; Sahbaie, P; Shi, XY; Tawfik, VL, 2019)	3.4
"Morphine-treated rats also displayed increased FHC levels in layer 2/3 neurons of the prefrontal cortex."	( Morphine-Induced Modulation of Endolysosomal Iron Mediates Upregulation of Ferritin Heavy Chain in Cortical Neurons. Datta, G; Festa, L; Geiger, JD; Halcrow, P; Irollo, E; Luchetta, J; Meucci, O; Nash, B; Tarn, K, )	2.3
"Morphine treatment is not associated with the incidence of osteoporosis, and bisphosphonates accentuated the protective effect of morphine in the development of osteoporosis in female patients with malignancy in Taiwan."	( Bisphosphonate treatment may reduce osteoporosis risk in female cancer patients with morphine use: a population-based nested case-control study. Chang, SN; Chang, YJ; Kao, CH; Lee, CW; Liang, JA; Muo, CH, 2013)	2.06
"In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity."	( Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin. Baker, AL; Carlton, SM; Hogan, D; Morón, JA, 2013)	1.32
"Morphine treatment activates microglia and astrocytes in the nucleus accumbens (NAcc) to induce the synthesis of cytokines and chemokines, and this has important implications for addictive behavior."	( FACS analysis of neuronal-glial interactions in the nucleus accumbens following morphine administration. Bilbo, SD; Schwarz, JM; Smith, SH, 2013)	1.34
"Morphine treatment of transgenic mice resulted in phosphorylation of PDGFR-β, MAPK/ERK, and signal transducer and activator of transcription 3 (Stat3) in the kidneys."	( Morphine stimulates platelet-derived growth factor receptor-β signalling in mesangial cells in vitro and transgenic sickle mouse kidney in vivo. Chen, C; Farooqui, M; Gupta, K; Hebbel, RP; Li, Y; Nguyen, J; Poonawala, T; Weber, ML, 2013)	2.55
"Morphine pretreatment prevented TLR4-dependent ERK and IKK phosphorylation."	( Morphine prevents lipopolysaccharide-induced TNF secretion in mast cells blocking IκB kinase activation and SNAP-23 phosphorylation: correlation with the formation of a β-arrestin/TRAF6 complex. Cruz, SL; Gonzalez-Espinosa, C; Madera-Salcedo, IK, 2013)	2.55
"In morphine-treated animals, all factors were increased after application of acute and subchronic stress, and conditioning scores also decreased after stress."	( Changes in the levels of p-ERK, p-CREB, and c-fos in rat mesocorticolimbic dopaminergic system after morphine-induced conditioned place preference: the role of acute and subchronic stress. Alamdary, SZ; Fatahi, Z; Haghparast, A; Khodagholi, F; Reisi, Z, 2014)	1.13
"Morphine-treated animals showed reduction in callus strength at 8 weeks (30% of the contralateral unfractured femur strength compared with 49% seen in the control animals at 8 weeks; p = 0.048); this finding was not fully reversed by testosterone supplementation (33% of the contralateral femur strength; p = 0.171)."	( Evaluating the affect and reversibility of opioid-induced androgen deficiency in an orthopaedic animal fracture model. Chrastil, J; Higgins, TF; Jones, KB; Sampson, C, 2014)	1.12
"Morphine treatment is associated with a modest increase in risk of ACS in patients with malignancy, but this association displays low significance in specific cancer types."	( Modest increase in risk of acute coronary syndrome associated with morphine use in cancer patients: a population-based nested case-control study. Kao, CH; Lee, CW; Liang, JA; Muo, CH; Sung, FC, 2014)	2.08
"Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe."	( Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model. Cao, L; McLane, VD; Willis, CL, 2014)	2.57
"Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region."	( The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT. Adriaens, A; Croubels, S; De Spiegeleer, B; Duchateau, L; Eersels, J; Peremans, K; Polis, I; Van Dorpe, S; Vermeire, S; Waelbers, T, 2014)	1.4
"Morphine treatment resulted in increased tumour angiogenesis, peri-tumoural lymphangiogenesis, mast cell activation, and higher levels of cytokines and SP in tumours."	( Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Gupta, K; Gupta, P; Li, Y; Luk, K; Nguyen, J; Robiner, S; Saavedra, R; Soto, W; Vang, D; Vincent, L, 2014)	2.57
"Morphine treatment also reduced lipid peroxidation and totally prevented increases in nitrite levels in those cells."	( Morphine protects against methylmercury intoxication: a role for opioid receptors in oxidative stress? Almeida, MB; Costa-Malaquias, A; Crespo-Lopez, ME; do Nascimento, JL; Macchi, Bde M; Souza Monteiro, JR, 2014)	2.57
"Morphine pretreatment prevented the occurrence of withdrawal CPA and withdrawal jumping, while clonidine (an α2 adrenergic receptor agonist) only blocked withdrawal CPA."	( Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice. Cravatt, BF; Damaj, MI; Gamage, TF; Ignatowska-Jankowska, BM; Lichtman, AH; Muldoon, PP, 2015)	1.38
"Morphine-treated rats showed a decrease in all markers used to determine neuronal degeneration compared to saline-treated rats."	( Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury. Avdoshina, V; Campbell, LA; Day, C; Lim, ST; Mocchetti, I, 2015)	1.14
"Morphine treatment potentiated LPS-induced vesicular translocation of GFP-LC3 with a concurrent increase in LC3-II levels. "	( Morphine potentiates LPS-induced autophagy initiation but inhibits autophagosomal maturation through distinct TLR4-dependent and independent pathways. Anand, V; Ma, J; Ramakrishnan, S; Roy, S; Wan, J, 2015)	3.3
"Morphine-treated animals underwent 10 days of morphine weaning to reduce the potential for observable physical signs of withdrawal."	( Long-term behavioral effects in a rat model of prolonged postnatal morphine exposure. Bajic, D; Craig, MM, 2015)	1.37
"The morphine-treated group showed significant decrements in the percentage maximum possible effect (%MPE) on days 5 and 7 compared to the first day, illustrating morphine tolerance. "	( Salvia officinalis L. attenuates morphine analgesic tolerance and dependence in rats: possible analgesic and sedative mechanisms. Emamjomeh, A; Hasanein, P; Teimuri Far, M, 2015)	1.26
"In morphine-treated rats, ICV oxytocin did not affect the mean firing rate of medial NAcSh neurons."	( Oxytocin excites nucleus accumbens shell neurons in vivo. Brown, CH; Hyland, BI; Moaddab, M, 2015)	0.93
"Morphine is effective treatment for neuropathic pain but produces tolerance on chronic use."	( Anti-hyperalgesic and anti-nociceptive potentials of standardized grape seed proanthocyanidin extract against CCI-induced neuropathic pain in rats. Bedi, O; Deshmukh, R; Kaur, G; Kumar, P; Sharma, N; Singh, S, 2016)	1.16
"Morphine treatment significantly elicited ERK phosphorylation and downregulated the expression level of α1 adrenoceptors in the VLO."	( The α1 adrenoceptors in ventrolateral orbital cortex contribute to the expression of morphine-induced behavioral sensitization in rats. Gao, HY; Huo, FQ; Li, T; Liang, F; Wei, L; Yan, CX; Zhang, YX; Zhu, YM, 2016)	1.38
"Morphine treatment before LPS challenge suppressed lethal endotoxic shock."	( Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice. Fukada, T; Kato, H; Ozaki, M; Yagi, J, 2016)	1.46
"morphine treatment. This article reviews the potential mechanism of spinally mediated nociceptive behaviors evoked by i.t."	( [Study of Supplementary Analgesics Capable of Reducing the Dosage of Morphine]. Komatsu, T, 2016)	1.39
"Morphine treatment produced antinociceptive tolerance, which was attenuated by co-administration of Chembridge-5861528 that alone had no effect on hot-plate latencies. "	( Potential role of spinal TRPA1 channels in antinociceptive tolerance to spinally administered morphine. Fan, H; Li, TF; Li, XY; Ma, AN; Pertovaara, A; Wang, YX; Wei, H; Wu, HY, 2016)	2.1
"In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent."	( Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats. Akella, A; Deshpande, SB; Rai, OP; Tiwari, AK, )	2.09
"Morphine treatment reduced the median H1975 cell number by approximately 23% (P = 0.03)."	( Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor: An In Vitro and Human Lung Tissue Study. Ahn, HJ; Chae, HB; Kim, J; Kim, JK; Kim, JY; Lee, SH, 2016)	2.6
"Morphine is often the treatment of choice for severe cancer-related pain. "	( Does Opioid Use Cause Angiogenesis and Metastasis? Abd-Elsayed, A; Grandhi, RK; Lee, S, 2017)	1.9
"Morphine-treated rats had similar behaviours to NaCl rats, but their RGS scores were significantly different over time and between treatments."	( Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats. Flecknell, P; Haylor, K; Leach, M; Malik, A; Miller, A; Roughan, J; Sandersen, C; Thomas, A, 2016)	1.46
"Morphine treatment was performed according to the standard method, including titration (NCCN Guidelines™, Adult Cancer Pain)."	( Expectation of a Decrease in Pain Affects the Prognosis of Pain in Cancer Patients: a Prospective Cohort Study of Response to Morphine. Fujita, Y; Koyama, A; Makimura, C; Matsuoka, H; Nakagawa, K; Nishio, K; Sakai, K; Sakamoto, R; Tsurutani, J; Yoshiuchi, K, 2017)	1.38
"Morphine-treated animals exhibited increased anxiety levels, impaired object location memory, and reduced hippocampal BDNF."	( Low- and high-intensity treadmill exercise attenuates chronic morphine-induced anxiogenesis and memory impairment but not reductions in hippocampal BDNF in female rats. Ahmadalipour, A; Alizadeh, M; Ghodrati-Jaldbakhan, S; Miladi-Gorji, H; Rashidy-Pour, A; Vafaei, AA, 2017)	1.42
"of morphine. Animals pre-treated with morphine and their vehicle controls were administered with 150 microg/kg i.v."	( Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission. Cadoni, C; Di Chiara, G; Valentini, V, 2008)	1.08
"Morphine-treated cats were given morphine sulphate by cervical subcutaneous injection twice daily for 10 days, whereas saline-treated cats received injections of 0.9% saline instead."	( Chronic morphine exposure affects visual response latency of the lateral geniculate nucleus in cats. He, L; Liang, Z; Long, Z; Zhou, Y, 2008)	1.5
"Morphine treatment decreases Bax and Hsp70 levels in cultured rat primary neurons, suggesting morphine may have a protective role in staurosporine and serum deprivation induced cytotoxicity."	( Prolonged morphine application modulates Bax and Hsp70 levels in primary rat neurons. Chen, Q; Cui, J; Yu, LC; Zhang, Y, 2008)	1.47
"Morphine treatment (5 mg/kg, i.v.) increased activity in evoked ACC neurons."	( Electrically and mechanically evoked nociceptive neuronal responses in the rat anterior cingulate cortex. Chen, WF; Shih, HC; Shyu, BC, 2008)	1.07
"Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003)."	( Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Agarwal, S; Clark, MR; Haythornthwaite, JA; Klick, B; Max, MB; Raja, SN; Tella, PK; Wu, CL, 2008)	2.51
"Morphine treatment increased MDA levels."	( Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of alpha-lipoic acid administration. Cighetti, G; Pinelli, A; Trivulzio, S, 2008)	1.29
"Morphine treatment 18 hours after reperfusion did not change the amount of injury."	( Effects of intravitreal morphine administered at different time points after reperfusion in a rabbit model of ischemic retinopathy. Asadi-Amoli, F; Dehpour, AR; Kiumehr, S; Riazi-Esfahani, M, 2009)	1.38
"morphine 7.5 mg; both treatments demonstrated rapid onset of efficacy, generally persistent throughout the 6-h assessment period."	( The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model. Babul, N; Carr, DB; Christensen, KS; Cohen, AE; Hamilton, DA; McNicol, E; Mermelstein, FH, 2008)	1.31
"Morphine treatment induced both motor activity and Fos immunoreactivity in the NAc, ACg and PrL suggesting that behavioral stimulation is produced by neural activation in these regions."	( Intra-VTA adenosine A1 receptor activation blocks morphine stimulation of motor behavior and cortical and limbic Fos immunoreactivity. Fan, W; Kaplan, GB; Klufas, MA; Leite-Morris, KA, 2009)	1.33
"Yet, morphine-treated mice placed in the safe side never even entered the TMT side; thus, these mice appeared to exhibit a behavioural response that is classically interpreted as increased fear, that is, spending significantly less time in the TMT side versus the controls."	( Morphine-induced stereotyped thigmotaxis could appear as enhanced fear and anxiety in some behavioural tests. Buckman, SG; Eitan, S; Hodgson, SR; Hofford, RS; Wellman, PJ, 2010)	2.26
"The morphine treatment also significantly increased DOR proteins in CeA preparations of synaptosomes."	( Rewarding morphine-induced synaptic function of delta-opioid receptors on central glutamate synapses. Bie, B; Pan, ZZ; Zhu, W, 2009)	1.24
"Morphine and capsaicin treatment produced both a significant decrease in the cerebral infarct size and a reversal of I/R-induced impairment of memory and motor-coordination."	( Pharmacological preconditioning of the brain: a possible interplay between opioid and calcitonin gene related peptide transduction systems. Jaggi, AS; Rehni, AK; Singh, N; Singh, TG, )	0.85
"Morphine pretreatment produced an increase in GABA levels and a decrease in glutamate levels in the first few minutes."	( [Effect of a simple morphine system injection in some aminoacids in the anterior cingulate cortex during acute pain]. Hernández, L; Páez, X; Quiñones, B; Silva, E, 2008)	1.39
"Morphine treatment increased free malondialdehyde and decreased vitamin E levels. "	( Morphine or its withdrawal affects plasma malondialdehyde, vitamin E levels and absence or presence of abstinence signs in rats. Accinni, R; Cighetti, G; Pinelli, A; Trivulzio, S, 2009)	3.24
"In morphine-treated rats, rPER1 and rPER2 expression in the SCN, basolateral amygdala, and nucleus accumbens shell showed robust circadian rhythms that were essentially identical to those in control rats."	( Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in rats. Jiang, WG; Li, SX; Liu, LJ; Lu, L, 2009)	2.31
"In morphine-pretreated rats (10mg/kg during 5 days), a challenge dose of the opiate induced a robust psychomotor sensitization at early withdrawal (3 days, SW 3), but not after a prolonged abstinence period (14 days), which was coincident with an accelerated dopamine turnover in the striatum."	( The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity. Esteban, S; García-Sevilla, JA; Ramos-Miguel, A, 2010)	1.16
"With morphine treatment, the levels of both cytoplasmic and nuclear E2F1 which is the downstream effecter of AKT were elevated and the interaction of E2F1 with YY1, rather than Sp1, was also increased."	( Mechanisms involved in phosphatidylinositol 3-kinase pathway mediated up-regulation of the mu opioid receptor in lymphocytes. Guo, L; Jiang, W; Li, C; Li, G; Li, H; Li, M; Liu, H; Liu, X; McNutt, MA; Wang, S, 2010)	0.82
"Morphine treatment resulted in a significant delay and reduction in both neutrophil and macrophage recruitment to the wound site."	( Chronic morphine administration delays wound healing by inhibiting immune cell recruitment to the wound site. Barke, RA; Charboneau, R; Koodie, L; Krishnan, AG; Martin, JL; Roy, S, 2010)	1.52
"Morphine-treated rats (10 mg/kg/12 h) received naloxone (3.2 mg/kg) in a novel environment (conditioned stimuli [CS]). "	( Precipitated and conditioned withdrawal in morphine-treated rats. Becker, GL; France, CP; Gerak, LR; Koek, W; Li, JX, 2010)	2.07
"Morphine-treated cultures on tissue culture plastic, collagen types I and IV and fibronectin, but not on laminin, covered less substrate than untreated cultures; individual cells were difficult to distinguish and their nuclei piled up in contrast to untreated cultures."	( Opioids affect focal contact-mediated cell-substrate adhesion. Bracke, ME; Debruyne, DJ; Mareel, MM, 2010)	1.08
"Morphine/naltrexone treatment was generally well tolerated in adult patients with chronic moderate to severe nonmalignant pain in clinical trials of up to 1-year duration."	( Morphine/naltrexone. Duggan, ST; Scott, LJ, 2010)	2.52
"Morphine treated animals gain significantly less weight than placebo implanted controls."	( Changes in metabolic-related variables during chronic morphine treatment. Ferenczi, S; Földes, A; Kovács, KJ; Márkus, VL; Martín, F; Milanés, MV; Núñez, C; Pintér-Kübler, B, 2010)	1.33
"Morphine treatment for 5 days protects heart against ischemia-reperfusion (IR) injury. "	( Nitric oxide and renal protection in morphine-dependent rats. Ajami, M; Babakoohi, S; Ebrahimi, SA; Habibey, R; Hesami, A; Pazoki-Toroudi, H, 2010)	2.08
"Morphine treatment resulted in a significant decrease in the expression and nuclear translocation of HIF-1 alpha with a concurrent suppression in vascular endothelial growth factor (VEGF) synthesis."	( Chronic morphine treatment inhibits LPS-induced angiogenesis: implications in wound healing. Barke, RA; Charboneau, R; Martin, JL; Roy, S, 2010)	1.52
"Morphine treatment for ∼20 h increased the colocalization of GIRK2 with PSD95, a dendritic spine marker."	( Morphine- and CaMKII-dependent enhancement of GIRK channel signaling in hippocampal neurons. Bahima, L; Lalive, AL; Luján, R; Lüscher, C; Nassirpour, R; Slesinger, PA, 2010)	2.52
"Morphine and saline treatment lasted for six days, respectively."	( Effect of morphine on conditioned place preference in rhesus monkeys. Carlson, S; Duan, W; Hu, X; Jiang, H; Li, C; Liu, C; Ma, H; Ma, Y; Wang, J; Wei, J; Wu, X; Yu, C, 2012)	1.5
"In morphine-treated animals, recovery from acute [Met](5)enkephalin-induced desensitization and receptor recycling was diminished."	( Recovery from mu-opioid receptor desensitization after chronic treatment with morphine and methadone. Lau, EK; Quillinan, N; Virk, M; von Zastrow, M; Williams, JT, 2011)	1.11
"Morphine treatment gradually and significantly decreased the NCAM expression levels."	( Involvement of NCAM and FGF receptor signaling in the development of analgesic tolerance to morphine. Fujita-Hamabe, W; Nakamoto, K; Tokuyama, S, 2011)	1.31
"In morphine-treated animals, evoked spinal neuronal responses were enhanced to a subset of thermal and mechanical stimuli. "	( Pregabalin suppresses spinal neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Bannister, K; Bauer, CS; Dickenson, AH; Dolphin, AC; Porreca, F; Sikandar, S, 2011)	0.99
"In morphine-treated animals, however, progesterone concentrations were consistently and significantly increased from days 18-20 of treatment."	( Morphine-induced changes in opioid sensitivity in postpartum females: a unique progesterone response. Anselmo-Franci, JA; Canteras, NS; Cruz, AM; de Oliveira, CA; Felicio, LF; Felippe, EC; Sukikara, MH, 2011)	2.33
"Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1."	( Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection. Adler, MW; Breslow, JM; Daly, JM; Eisenstein, TK; Gaughan, J; Meissler, JJ; Monroy, MA, 2011)	2.53
"Morphine treatment decreased this ratio to 0.48±0.03 indicating a shift of WLS from the intracellular compartment to the plasma membrane."	( Opiate agonist-induced re-distribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons. Berrettini, WH; Ferraro, TN; Levenson, R; Reyes, BA; Vakharia, K; Van Bockstaele, EJ, 2012)	1.1
"Morphine treatment resulted in a shift of the brain sources in the low-frequency range (2-4 Hz) toward the frontal cortex during the first 300 milliseconds after stimulus, whereas active brain sources after placebo treatment remained stable."	( Advanced pharmaco-EEG reveals morphine induced changes in the brain's pain network. Brock, C; Drewes, AM; Lelic, D; Olesen, AE; Staahl, C, 2012)	2.11
"Morphine treatment appreciably affected neither the number of myocardial β-adrenoceptors nor the content of selected subunits of trimeric G-proteins (G(s)α, G(i/o)α, G(z)α, G(q/11)α and Gβ) but the amount of the dominant myocardial AC isoform V/VI almost doubled. "	( Antiarrhythmic effect of prolonged morphine exposure is accompanied by altered myocardial adenylyl cyclase signaling in rats. Bartonova, I; Hejnova, L; Kolar, F; Neckar, J; Novotny, J; Skrabalova, J, 2012)	2.1
"The morphine-treated patients experienced clinically relevant improvements in pain relief, as shown by a 44% reduction in average visual analogue scale pain levels and a 31% improvement in functional ability."	( Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain. Angst, MS; Brady, C; Chu, LF; Clark, DJ; Clemenson, AM; D'Arcy, N; Kim, JE; Young, CA; Zamora, AK, 2012)	1.06
"Morphine pretreatment at 100 µg kg(-1) (i.v.) or 10 µg (i.t.) reduced necrosis, apoptosis, and serum transaminase levels, and increased phosphorylated Akt and STAT3 but not JAK2 expression in normal liver. "	( Pretreatment with intrathecal or intravenous morphine attenuates hepatic ischaemia-reperfusion injury in normal and cirrhotic rat liver. Irwin, MG; Man, K; Wang, Y; Wong, GT, 2012)	2.08
"Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS."	( Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis. Buch, S; Chandel, N; Husain, M; Malhotra, A; Salhan, D; Sharma, B; Singhal, PC, 2012)	1.32
"Morphine treatment was found, using immunohistochemistry, to increase ASM expression and intracellular ceramide in the periaqueductal gray 30 min after an acute injection (10 mg/kg)."	( Contribution of acid sphingomyelinase in the periaqueductal gray region to morphine-induced analgesia in mice. Dewey, WL; Fang, Y; Li, PL; Ritter, JK; Xia, M, 2012)	1.33
"Morphine is the basic treatment."	( [Sickle-cell anemia and pain]. de la Brière, A, )	0.85
"Morphine pretreatment enhanced ERK phosphorylation, but inhibited IκBα phosphorylation and IL-2 gene expression in activated T cells. "	( Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes. Fukuda, K; Mizota, T; Shoda, T; Tsujikawa, H, 2013)	2.06
"Morphine treatment in differentiated SH-SY5Y cells caused significant downregulation of MOR-1 expression compared to the control cells."	( Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine. Badisa, RB; Goodman, CB; Luscar, E; Prenus, RV; Zhu, ZP, 2012)	1.32
"Morphine treatment (10mg/kg, i.p."	( Melanocortin 4 receptor antagonists attenuates morphine antinociceptive tolerance, astroglial activation and cytokines expression in the spinal cord of rat. Cheng, Y; Chu, H; Feng, W; Ma, J; Niu, Z; Zhao, Y, 2012)	1.36
"Morphine treatment can eliminate augmented breaths (ABs; 'sighs') during spontaneous breathing. "	( Augmented breaths ('sighs') are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats. Bell, HJ; Pankuch, G, 2013)	2.09
"Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. "	( Dual effect of morphine in long-term social memory in rat. Bianchi, E; Ghelardini, C; Menicacci, C, 2013)	2.19
"Morphine-treated children showed significantly fewer problems with executive functions in daily life as rated by parents for the subscales inhibition and organization of materials and for planning/organizing as rated by the teachers."	( Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age? Anand, KJS; de Graaf, J; Jebbink, LG; Tibboel, D; Valkenburg, AJ; van Dijk, M; van Lingen, RA; Weisglas-Kuperus, N; Wijnberg-Williams, B, 2013)	1.47
"Morphine treatment after training also caused a decrease in this latency when tested after 24 h."	( Effects of morphine on associative memory and locomotor activity in the honeybee (Apis mellifera). Chen, Y; Fu, Y; Li, P; Ma, Y; Wang, J; Yao, T, 2013)	1.5
"morphine treatment for all chronic i.t."	( Attenuation of morphine tolerance after antisense oligonucleotide knock-down of spinal mGluR1. Coderre, TJ; Fundytus, ME; Osborne, M; Sharif, RN, 2002)	1.39
"Morphine treatment of 5 days and longer induced significant increases in levels of Galpha(o), Galpha(i1), and Galpha(i2) in MI fractions that are part of an adaptation process."	( Chronic morphine-induced changes in mu-opioid receptors and G proteins of different subcellular loci in rat brain. Bozó, B; Coscia, CJ; Fábián, G; Horváth, G; Szikszay, M; Szücs, M, 2002)	1.47
"Morphine pretreatment, however, significantly reduced NSIA dependence on intra-accumbens opioid receptors but not on dopamine or nicotinic acetylcholine receptors."	( Altered nucleus accumbens circuitry mediates pain-induced antinociception in morphine-tolerant rats. Barletta, J; Gear, RW; Green, P; Levine, JD; Luo, L; Schmidt, BL; Tambeli, CH, 2002)	1.26
"Morphine treated subjects showed a significant decrease (P<0.05) in striatal dopamine concentration, whilst cocaine and sertraline treatment resulted in a significant increase in striatal dopamine levels."	( Morphine, cocaine and antidepressant induced motivational activity and midbrain dopaminergic neurotransmission. Buckland, P; Deslandes, PN; Pache, DM; Sewell, RD, 2002)	2.48
"In morphine-treated cells, morphine stimulated [(35)S]-GTP-gamma-S binding by decreasing the high-affinity K(d) without changing the B(max)."	( Opioid peptide receptor studies. 16. Chronic morphine alters G-protein function in cells expressing the cloned mu opioid receptor. Lu, YF; Rothman, RB; Xu, H, 2003)	1.09
"Morphine treatment produced significant tolerance (ED(50) shift approximately 9-fold), but no mu-opioid receptor downregulation."	( Role of G(i)alpha2-protein in opioid tolerance and mu-opioid receptor downregulation in vivo. Gomes, BA; Patel, C; Patel, M; Rajashekara, V; Yoburn, BC, 2003)	1.04
"morphine in LPS-treated rats compared to controls."	( Enhanced thermal antinociceptive potency and anti-allodynic effects of morphine following spinal administration of endotoxin. Cahill, CM; Coderre, TJ; Dray, A, 2003)	1.27
"Morphine pretreatment protects against stress-induced gastric ulceration, however, the exact mechanism is still undefined. "	( Morphine as a drug for stress ulcer prevention and healing in the stomach. Cho, CH; Chu, KM; Liu, ES; Shin, VY; So, WH; Wong, BC; Wong, TM; Wu, KK; Wu, S; Ye, YN, 2003)	3.2
"Morphine treatment (10 microM) for 24 h decreased MOR mRNA levels in control, as well as RA- and TPA-differentiated cells."	( Morphine and endomorphins differentially regulate micro-opioid receptor mRNA in SHSY-5Y human neuroblastoma cells. Blake, AD; Chang, SL; Li, WX; Mao, X; Yu, X, 2003)	2.48
"In morphine-treated monkeys, buprenorphine and not nalbuphine substituted for naltrexone."	( Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone. France, CP; McMahon, LR; Sell, SL, 2003)	1.08
"Morphine treatment for 7 days resulted in the development of tolerance to morphine's analgesic effect and produced a significant decrease in the steady-state NR1 mRNA levels in the spinal cord dorsal horn (by 16%), and an elevation in nucleus raphe magnus and medial thalamus (by 26 and 38%, respectively)."	( Region-specific changes in NMDA receptor mRNA induced by chronic morphine treatment are prevented by the co-administration of the competitive NMDA receptor antagonist LY274614. Brodsky, M; Gorman, AL; Inturrisi, CE; Zhu, H, 2003)	1.28
"Morphine treatment over 4 days induced tolerance as reflected on the hot-plate test by a significant reduction of paw-withdrawal latency from 242% to 99% above baseline."	( Mu-opioid receptor mRNA regulation during morphine tolerance in the rat peripheral nervous system. Gabriel, A; Giesecke, T; Grond, S; Hescheler, J; Horsch, M; Meuser, T; Palmer, PP; Sabatowski, R, 2003)	1.3
"Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped."	( Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers. Barr, MC; Henriksen, SJ; Huitron-Resendiz, S; Phillips, TR; Sanchez-Alavez, M, 2003)	1.43
"Morphine pretreatment was administered as a constant infusion, which was gradually increased to a dose of 50 mg/kg/day over a 1-week period in Wistar rats."	( Long-term opiate effects on amphetamine-induced dopamine release in the nucleus accumbens core and conditioned place preference. Grasing, K; He, S; Li, N, 2004)	1.04
"morphine pretreatment also attenuated the TF inhibition produced by opioid muagonist [D-Ala2, N-Me-Phe4,Gly-ol5]-enkephalin, delta-agonist deltorphin II, and kappa-agonist U50,488H."	( Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord. Fujimoto, JM; Leitermann, RJ; Sun, HS; Thompson, J; Tseng, LF; Wu, HE, 2004)	1.32
"Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment."	( Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty. Bridges, RS; Byrnes, EM; Rigero, BA, 2003)	1.27
"morphine (1 mg/kg). Pretreatment with a selective MOR antagonist (clocinnamox, 0.1 mg/kg), but not kappa or delta opioid antagonists (nor-binaltorphimine or naltrindole), blocked i.t."	( The role of central mu opioid receptors in opioid-induced itch in primates. Edwards, T; Ko, MC; Lee, H; Naughton, NN; Song, MS, 2004)	1.04
"Morphine treatment increased the EC50 (6.2-fold) for DAMGO-mediated inhibition of forskolin-stimulated cAMP activity in control cells but not in cells treated with AS-114 to knock-down RGS9."	( Opioid peptide receptor studies. 17. Attenuation of chronic morphine effects after antisense oligodeoxynucleotide knock-down of RGS9 protein in cells expressing the cloned Mu opioid receptor. Rothman, RB; Wang, J; Wang, X; Xu, H, 2004)	1.29
"Morphine pre-treatment resulted in a moderate but significant increase in sensitivity of NIH-3T3 cells to vinblastine, but not colchicine."	( Effect of short-term morphine exposure on P-glycoprotein expression and activity in cancer cell lines. Bebawy, M; Hoskins, JM; Pajic, M; Rivory, LP; Roufogalis, BD, 2004)	1.36
"Morphine pretreatment via activation of delta1-opioid receptors induces cardioprotection. "	( Morphine preconditions Purkinje cells against cell death under in vitro simulated ischemia-reperfusion conditions. Lim, YJ; Zheng, S; Zuo, Z, 2004)	3.21
"The morphine-treated groups did not differ, suggesting that morphine attenuates hypersensitivity to formalin pain in the SHR."	( Morphine-induced analgesia, hypotension, and bradycardia are enhanced in hypertensive rats. Lovell, BM; Mahinda, TB; Taylor, BK, 2004)	2.25
"In morphine-treated animals, before neutrophil recruitment, a significant decrease in TNF-alpha, IL-1, IL-6, MIP-2, and KC was observed both in bronchoalveolar lavage fluids and in lung tissue."	( Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. Barke, RA; Charboneau, R; Roy, S; Wang, J, 2005)	2.29
"morphine treatment did not lead to increases in glial activation markers."	( Transcriptional and translational regulation of glial activation by morphine in a rodent model of neuropathic pain. DeLeo, JA; LaCroix-Fralish, ML; Nutile-McMenemy, N; Tawfik, VL, 2005)	1.29
"The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. "	( Expression of opioid receptor-like 1 (ORL1) & mu opioid receptors in the spinal cord of morphine tolerant mice. Gupta, YK; Ray, SB; Wadhwa, S, 2005)	1.11
"Morphine treatment recruited RGS4 to the PAG membranes, and 30 min and 3 h after the opioid challenge its association with mu receptors had increased."	( Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter. Garzón, J; Rodríguez-Muñoz, M; Sánchez-Blázquez, P, 2005)	2.49
"In morphine-treated animals, concentration-effect curves for ME in the locus coeruleus were shifted by 5-fold to the right as compared to those in sham-treated animals, which confirmed the induction of mu-opioid receptor tolerance."	( Inhibition of neuronal nitric oxide synthase attenuates the development of morphine tolerance in rats. Pineda, J; Santamarta, MT; Ulibarri, I, 2005)	1.07
"Morphine-withdrawn LPS-treated animals had elevated serum TNF-alpha and nitric oxide levels, and depressed IL-12 levels compared to controls."	( Morphine withdrawal sensitizes mice to lipopolysaccharide: elevated TNF-alpha and nitric oxide with decreased IL-12. Adler, MW; Eisenstein, TK; Feng, P; Meissler, JJ, 2005)	2.49
"Morphine treatment had no significant effect on PAR-1 thrombin receptor-activated G protein activity, as measured by thrombin-stimulated guanosine 5'-O-(3-[35S]thio)triphosphate binding."	( Chronic morphine up-regulates G alpha12 and cytoskeletal proteins in Chinese hamster ovary cells expressing the cloned mu opioid receptor. Bilsky, EJ; Boja, ES; Rothman, RB; Wang, J; Wang, X; Xu, H; Zimmerman, D, 2005)	1.48
"Morphine treatment (10mg/kg, i.p."	( Inhibition of morphine tolerance by spinal melanocortin receptor blockade. Obara, I; Przewlocka, B; Przewłocki, R; Starowicz, K, 2005)	1.41
"Morphine and LPS treatment increased phosphorylation of the inhibitory protein kappaB, leading to an increased activity of NF-kappaB."	( Morphine induces late cardioprotection in rat hearts in vivo: the involvement of opioid receptors and nuclear transcription factor kappaB. Frässdorf, J; Kojda, G; Müllenheim, J; Obal, D; Preckel, B; Schlack, W; Toma, O; Weber, NC, 2005)	2.49
"The morphine-treated group showed a significant increase in mu receptor binding on P1 and P7."	( Effects of prenatal cocaine, morphine, or both on postnatal opioid (mu) receptor development. Bhat, R; Chari, G; Rao, R, 2006)	1.11
"Morphine pretreatment induces ischemic tolerance in neurons, but it remains uncertain whether novel protein kinase C epsilon isoform (nPKCepsilon) and N-methyl-D-aspartate (NMDA) receptors are involved in this neuroprotection. "	( nPKCepsilon and NMDA receptors participate in neuroprotection induced by morphine pretreatment. Bingxi, Z; Fang, J; Fanjun, M; Junfa, L, 2006)	2.01
"Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the micro-opioid receptor than did wild-type mice, while uncoupling was similar in control wild-type and KO mice."	( Evidence for a role of CaMKIV in the development of opioid analgesic tolerance. Chatila, T; Jang, DH; Jia, Y; Kaang, BK; Ko, SW; Lee, YS; Toyoda, H; Wu, LJ; Xu, H; Yim, SJ; Zhao, MG; Zhuo, M, 2006)	1.06
"Morphine pre-treatment significantly reduced mortality upon i.v."	( Toxicological analysis in rats subjected to heroin and morphine overdose. Alkass, K; Druid, H; Gustavsson, A; Kugelberg, FC; Spigset, O; Strandberg, JJ; Zahlsen, K, 2006)	1.3
"Morphine treatment increased the susceptibility to S."	( Enhancement of mice susceptibility to infection with Listeria monocytogenes by the treatment of morphine. Asakura, H; Igimi, S; Kawamoto, K; Makino, S; Yamamoto, S, 2006)	1.27
"Morphine treatment was also found to lead to a local increase in two other components of the endocytic machinery, dynamin and AP-2, suggesting a critical involvement of the endocytic machinery in the modulatory effects of morphine."	( Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: a proteomics study focusing on endocytic proteins. Abul-Husn, NS; Devi, LA; Dolios, G; Morón, JA; Rozenfeld, R; Wang, R, 2007)	2.5
"morphine. In mice treated with high-dose morphine, 7-NI was very effective in blocking ERK activation, whereas W1400 had no effect."	( Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior. Bagetta, G; Komatsu, T; Sakurada, C; Sakurada, S; Sakurada, T; Sanai, K; Sasaki, M; Tsuzuki, M, 2007)	1.28
"Morphine is the main treatment but the prescription of controlled-release morphine must be associated with the prescription of immediate-release morphine to treat the PPA or to transmucosal fentanyl which has a faster onset of action than immediate-release morphine."	( [Nociceptive cancer pain in adult patients: statement about guidelines related to the use of antinociceptive medicine]. Binhas, M; Krakowski, I; Marty, J, 2007)	1.06
"Morphine-treated dams decreased maternal behavior while increasing efficiency in hunting insects."	( Opiate regulation of behavioral selection during lactation. Canteras, NS; Felicio, LF; Platero, MD; Sukikara, MH, )	0.85
"Morphine treatment may result in "add-on" mechanisms of pain beyond those engaged by sarcoma alone."	( Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Cress, AE; King, T; Lai, J; Majuta, L; Melemedjian, O; Nagle, R; Porreca, F; Vanderah, TW; Vardanyan, A, 2007)	2.5
"Morphine treatment acutely suppressed the mechanical allodynia, but tolerance to this effect rapidly developed."	( Sciatic nerve cuffing in mice: a model of sustained neuropathic pain. Barrot, M; Benbouzid, M; Doridot, S; Freund-Mercier, MJ; Pallage, V; Poisbeau, P; Rajalu, M; Waltisperger, E, 2008)	1.07
"Morphine treatment reduced MIP-2 release in pneumococci stimulated alveolar macrophages."	( Morphine induces defects in early response of alveolar macrophages to Streptococcus pneumoniae by modulating TLR9-NF-kappa B signaling. Barke, RA; Charboneau, R; Roy, S; Schwendener, R; Wang, J, 2008)	2.51
"Morphine treatment initiated at the time of incision did not lead to a generalized enhancement of cytokine production or nociceptive sensitization in excess of the levels observed after incision alone."	( Chronic morphine administration enhances nociceptive sensitivity and local cytokine production after incision. Angst, MS; Clark, JD; Liang, D; Qiao, Y; Shi, X; Yeomans, DC, 2008)	1.5
"Morphine pretreatment provides significant histologic protection against ischemic injury in rabbit retina. "	( Morphine pretreatment provides histologic protection against ischemia-reperfusion injury in rabbit retina. Asadi-Amoli, F; Dehpour, AR; Kiumehr, S; Lashay, AR; Riazi-Esfahani, M, 2008)	3.23
"Morphine pretreatment attenuated subsequent excitatory responses to hypocretin, suggesting a long-lasting depression caused by opiate exposure."	( Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin arousal system. Li, Y; van den Pol, AN, 2008)	1.07
"morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIalpha immunoreactivity elicited by i.c.v."	( The differential effect of morphine and beta-endorphin administered intracerebroventricularly on pERK and pCaMK-II expression induced by various nociceptive stimuli in mice brains. Choi, HW; Jang, JE; Jung, JS; Kwon, MS; Lee, JK; Park, SH; Seo, YJ; Suh, HW, 2008)	1.36
"Morphine treatment can paradoxically increase nociception (i.e. "	( Sex differences in hyperalgesia during morphine infusion: effect of gonadectomy and estrogen treatment. Juni, A; Kest, B; Klein, G; Kowalczyk, B; Ragnauth, A, 2008)	2.06
"Morphine pretreatment however, failed to antagonize apomorphine-induced cage climbing behaviour thereby ruling out the possibility of its possessing DA receptor blocking activity."	( Involvement of histaminergic mechanisms in the cataleptogenic effect of morphine in mice. Balsara, JJ; Chandorkar, AG; Jadhav, JH; Muley, MP, 1982)	1.22
"Morphine treatment alone had no effects on the NA levels in any region studied."	( Effects of morphine on the 6-hydroxydopamine induced changes of the postnatal development of central noradrenaline neurons. Hallman, H; Jonsson, G, 1982)	1.38
"Morphine treatment in normal intact rats caused a dose-dependent increase in hepatic tyrosine aminotransferase (TAT) activity, as demonstrable up to 2 hr of exposure to the opioid alkaloid. "	( Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase. Chatterjee, TK; Das, S; Ghosh, JJ, 1984)	3.15
"Morphine pretreatment did not alter TSH stimulation by TRH."	( The role of opiates and endogenous opioid peptides in the regulation of rat TSH secretion. Briggs, J; Carlson, HE; Gordon, J; Hershman, JM; Melmed, S; Morley, JE; Sharp, B, 1981)	0.98
"Morphine (M) treatment has been shown to suppress LH release in rats. "	( Effects of intraventricular administration of catecholamines on luteinizing hormone release in morphine-treated rats. Gallo, RV; Kalra, SP, 1983)	1.93
"The morphine-treated mice manifested body weight loss, diarrhea and ptosis from 4 hr after morphine withdrawal and showed maximum body weight loss at 12 hr."	( Induction of physical dependence on morphine in mice by the drug-admixed food method. Suzuki, T; Yanaura, S; Yoshii, T, 1984)	1.02
"Morphine treatment elevated end-tidal PCO2 at both work levels (P < 0.05)."	( Morphine reduces ventilation without changing metabolic rate in exercise. Martin, BJ; Weil, JV; Zwillich, CW, 1980)	2.43
"Morphine treatment decreased the frequency of contractions in both areas of the small intestine."	( Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat. Burks, TF; Galligan, JJ, 1983)	1.22
"Morphine treatment during pregnancy was scheduled with the view to reproduce physical dependence in female rats and to investigate the occurrence of a neonatal withdrawal syndrome (NWS) as well as more prolonged effects of the narcotic in the preweaned pups. "	( Morphine treatment during rat pregnancy: neonatal and preweaning consequences. Lapointe, G; Nosal, G, 1982)	3.15
"No morphine-treatment was received in group A, treatment form the beginning of pregnancy (day 0) to weaning in group B, from day 0 to day 14 in group C, from day 15 to day 21 in group D, from day 0 to weaning in group E (the same of B), and no treatment in group F."	( [Effects of morphine on the successive generation]. Suzuki, T; Yanaura, S; Yoshii, T, 1981)	1.16
"In morphine-pretreated mice, naloxone caused a marked increase in the amplitude of the evoked e.j.p."	( The effect of chronic morphine treatment of excitatory junction potentials in the mouse vas deferens. North, RA; Vitek, LV, 1980)	1.09
"1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced by the antagonistic potency of naloxone. "	( The effect of chlorpromazine pretreatment on the narcotic antagonistic potency of naloxone in mice. Roberts, MB; Wai, MK; Wong, CL, )	0.75
"Morphine treatment significantly increased the number of 3H-thymidine labeled subependymal cells and number of grains/nucleus within labeled cells."	( Effect of morphine on 3H-thymidine incorporation in the subependyma of the rat: an autoradiographic study. Deadwyler, SA; Miller, CR; O'Steen, WK, 1982)	1.39
"Morphine treatment alone significantly disrupted the rate of onset and quality of maternal responsiveness."	( Reversal of morphine disruption of maternal behavior by concurrent treatment with the opiate antagonist naloxone. Bridges, RS; Grimm, CT, 1982)	1.36
"morphine treatment."	( Postoperative analgesia and lung function: a comparison of intramuscular with epidural morphine. Petersen, TK; Rybro, L; Schurizek, BA; Wernberg, M, 1982)	1.21
"1. Morphine pretreatment (2.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 3 h later, but enhanced the antagonistic potency of naloxone. "	( The effect of chlorpromazine pretreatment on morphine analgesia and naloxone potency in adrenalectomized mice. Wai, MK; Wong, CL, )	1.01
"1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced the antagonistic potency of naloxone. "	( Preliminary studies on increased naloxone potency and its relationship to morphine tolerance and dependence in mice. Roberts, MB; Wai, MK; Wong, CL, )	0.98
"Morphine pretreatment enhanced the antidipsogenic effects of naloxone in a dose- and time-dependent manner."	( Suppression of drinking by naloxone in rats homo- and heterozygous for diabetes insipidus. Brown, DR; Holtzman, SG, 1981)	0.98
"Morphine treatment of rats for 5 days was associated with a reduction in the amount of striatal RNA for the voltage-sensitive K+ channel without significant changes in other ion channels."	( Cellular adaptation to opiates alters ion-channel mRNA levels. Eberwine, JH; Mackler, SA, 1994)	1.01
"Morphine treatment increased striatal Met-enkephalin."	( The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in Sprague-Dawley rats. Nylander, I; Terenius, L; Vlaskovska, M, 1995)	1.37
"Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7."	( CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with morphine or naltrexone. Brodsky, M; Elliott, K; Hynansky, A; Inturrisi, CE, 1995)	1.24
"morphine treatment. A decrease in the number of binding sites (Bmax) with no change in the affinity (Kd) of the ligand for the adenosine A1 receptor was observed."	( Chronic intracerebroventricular administration of morphine down-regulates spinal adenosine A1 receptors in rats. Liu, CF; Tao, PL; Tsai, HC, 1995)	1.27
"Morphine treatment increased c-fos mRNA levels in striatum (STR) and amygdala (AMY)."	( NMDA antagonists and clonidine block c-fos expression during morphine withdrawal. Brodsky, M; Inturrisi, CE; Rasmussen, K, 1995)	1.25
"Morphine pretreatment attenuates aversive taste reactions elicited by quinine solution when assessed by the taste reactivity test. "	( Morphine-induced modification of quinine palatability: effects of multiple morphine-quinine trials. Clarke, SN; Parker, LA, )	3.02
"Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). "	( Morphine increases synchronous ventilation in preterm infants. Dyke, MP; Evans, S; Kohan, R, 1995)	3.18
"Morphine pretreatment was found to inhibit the release, and such inhibition was not prevented by naloxone."	( Morphine modulates contractile responses and neurokinin A-LI release elicited by electrical field stimulation or capsaicin in a guinea pig bronchial-tube preparation. Andersson, RG; Lindström, EG, 1995)	2.46
"Morphine treatment had no effect on basal secretion of LHRH, nor on the spontaneous, pulsatile release of LHRH."	( Opioid inhibition of adrenergic and dopaminergic but not serotonergic stimulation of luteinizing hormone releasing hormone release from immortalized hypothalamic neurons. Cameron, DF; Landon, CS; Muffly, KE; Nazian, SJ, 1994)	1.01
"Morphine treatment did not significantly change the number of cells expressing Fos immunoreactivity, or the percentage of TH-positive cells expressing Fos-like protein."	( Presynaptic actions of morphine: blockade of cholecystokinin-induced noradrenaline release in the rat supraoptic nucleus. Guevara-Guzman, R; Kendrick, K; Leng, G; Luckman, SM; Onaka, T; Ueta, Y, 1995)	1.32
"In morphine pellet treated mice the DPDPE/clonidine interaction decreased to an antagonistic interaction, the DAMGO/clonidine remained synergistic and the U50-488H/clonidine interaction decreased to additive."	( Decreased spinal morphine/clonidine antinociceptive synergism in morphine-tolerant mice. Roerig, SC, 1995)	1.14
"Morphine treated animals were similarly tested on the third day following the last morphine injection."	( Chronic variable stress or chronic morphine facilitates immobility in a forced swim test: reversal by naloxone. Heyser, CJ; Molina, VA; Spear, LP, 1994)	1.29
"Morphine treatment was associated with an increase in serum albumin, SGPT, BUN, and alkaline phosphatase indicative of hepatic damage."	( Immunotoxicological profile of morphine sulfate in B6C3F1 female mice. Brown, RD; Butterworth, LF; Harris, LS; LeVier, DG; McCay, JA; Munson, AE; Musgrove, DL; Page, D; Stern, ML; White, KL, 1994)	1.3
"Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79)."	( Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies. Dean, HG; Hartley, R; Levene, MI; Puntis, JW; Quinn, MW; Rushforth, JA; Wild, J, 1993)	1.26
"Morphine pre-treatment was less effective in preventing development of hyperalgesia; however, whilst the ipsilateral (146 +/- 18 g) paw withdrawal threshold tended to be lower than the contralateral (183 +/- 8 g), this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Pre-emptive administration of clonidine prevents development of hyperalgesia to mechanical stimuli in a model of mononeuropathy in the rat. Birch, PJ; Elliott, PJ; Harrison, SM; Smith, GD; Wiseman, J, 1993)	1.01
"Morphine pretreatment sensitized rats to naltrexone, lowering its ED50 from 20 to 0.03 mg/kg."	( Acute sensitization to opioid antagonists. Holtzman, SG; White-Gbadebo, D, 1994)	1.01
"Morphine treatment produced a decrease in body weight and spleen cell number."	( Spleen and thymus cell subsets modified by long-term morphine administration in protein-undernourished mice--I. Chen, GJ; Colombo, LL; Darban, HR; Huang, DS; Lopez, MC; Watson, RR; Watzl, B, 1993)	1.26
"Morphine treatment produced a decrease in body weight and spleen cell number."	( Spleen and thymus cell subsets modified by long-term morphine administration and murine AIDS--II. Chen, GJ; Colombo, LL; Darban, HR; Huang, DS; Lopez, MC; Watson, RR; Watzl, B, 1993)	1.26
"In morphine-treated neurons, the number of inhibitory G-proteins (G alpha i) appeared to be slightly reduced (by about 16%)."	( Adaptive changes in the number of Gs- and Gi-proteins underlie adenylyl cyclase sensitization in morphine-treated rat striatal neurons. Mulder, AH; Schoffelmeer, AN; Van Rijswijk, AL; Van Vliet, BJ; Wardeh, G, 1993)	1.02
"Morphine-treated rats, despite showing tolerance to morphine itself, showed no cross-tolerance to the inhibitory actions of U50,488 upon the oxytocin system."	( Effects of the selective kappa-opioid agonist U50,488 upon the electrical activity of supraoptic neurones in morphine-tolerant and morphine-naive rats. Leng, G; Pumford, KM; Russell, JA, 1993)	1.22
"Morphine treatment caused splenic atrophy and suppressed the primary in vitro antibody response in beige and beige+ mice."	( Effects of in vivo morphine treatment on antibody responses in C57BL/6 bgJ/bgJ (beige) mice. Adler, MW; Bussiere, JL; Eisenstein, TK; Rogers, TJ, 1993)	1.34
"In morphine-treated mice there was less 14C in liver, brain and blood, and more 3H in kidney and hindleg muscle than in control mice."	( Effect of intrathecal morphine on the fate of glucose. Comparison with effects of insulin and xanthan gum in mice. Brase, DA; Dewey, WL; Dombrowski, DS; Dunlow, LD; Ward, CR; White, CW, 1993)	1.11
"The morphine treatment also antagonized CCK-induced cessation of bile flow present in female guinea pigs."	( Effects of chronic morphine on biliary tract responses to cholecystokinin-octapeptide in female guinea pigs. Malave, A; Yim, GK, 1993)	1.1
"Morphine pretreatment (100 mg/kg, s.c., -5 hr) produced antinociceptive tolerance as shown by a 2.7-fold increase in the calculated morphine A50 value."	( Effects of naloxone and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 and the protein kinase inhibitors H7 and H8 on acute morphine dependence and antinociceptive tolerance in mice. Bernstein, RN; Bilsky, EJ; Porreca, F; Sadée, W; Wang, Z, 1996)	1.22
"Morphine treatment did not alter the response to lipopolysaccharide."	( Equianalgesic doses of subcutaneous but not intrathecal morphine alter phenotypic expression of cell surface markers and mitogen-induced proliferation in rat lymphocytes. Hamra, JG; Yaksh, TL, 1996)	1.26
"The morphine-pretreated animals showed faster acquisition of seizure activity."	( Effects of chronic morphine pretreatment on amygdaloid kindling development, postictal seizure and suppression and benzodiazepine receptor binding in rats. Ackermann, RF; Engel, J; Rocha, L, 1996)	1.1
"Morphine-treated pups tested with naltrexone showed significant alterations in behavior that varied at different ages."	( Ontogeny of morphine withdrawal in the rat. Barr, GA; Jones, KL, 1995)	1.39
"The morphine-treated mice showed tolerance to the drug after daily exposure over 5 days as determined by measuring tail flick latency during thermal application."	( Morphine suppresses the alloantigen-driven CTL response in a dose-dependent and naltrexone reversible manner. Carr, DJ; Scott, M, 1996)	2.22
"Post-morphine treatments with naloxone (1 mg/kg SC) at 0 (i.e., simultaneously with) to 30 min after each morphine administration almost completely inhibited the induction of morphine sensitization."	( Interval-dependent inhibition of morphine sensitization of ambulation in mice by post-morphine treatment with naloxone or restraint. Kuribara, H, 1996)	1.03
"Morphine treatment also increased the glutamate/GABA ratio in the striatum."	( Effects of morphine treatment and withdrawal on striatal and limbic monoaminergic activity and ascorbic acid oxidation in the rat. De Natale, G; Desole, MS; Enrico, P; Esposito, G; Fresu, L; Miele, E; Miele, M; Migheli, R; Mura, MA, 1996)	1.41
"Morphine treatment caused a significant decrease (15.6 +/- 5.8%) in mu-opioid receptor mRNA expression in the BH, while POA and THAL were not different from placebo controls."	( Downregulation of mu-opioid receptor mRNA in the mediobasal hypothalamus of the female guinea pig following morphine treatment. Bosch, MA; Cunningham, MJ; Grandy, DK; Kelly, MJ; Rønnekleiv, OK; Wagner, EJ, 1996)	1.23
"In morphine-treated rats, a challenge dose of morphine (30 mg/kg i.p.) increased the auricular noradrenaline, adrenaline and DA content and decreased dihydroxy phenyl acetic acid/DA ratio; these changes were accompanied by a decrease in the force of contraction in the isolated left atria."	( Effects of chronic morphine treatment on catecholamines content and mechanical response in the rat hearts. Laorden, ML; Milanés, MV; Rabadán, JV, 1997)	1.14
"Morphine-pretreated animals showed enhanced motor activity in response to intraaccumbens microinfusion of the psychostimulant drugs."	( Sensitization of the locomotor response to psychostimulants after repeated opiate exposure: role of the nucleus accumbens. Cunningham, ST; Finn, M; Kelley, AE, 1997)	1.02
"In morphine-pretreated rats, the antinociceptive effect of morphine on the vocalization threshold to paw pressure was greatly reduced, as compared to the saline-pretreated group."	( The antinociceptive activity of kappa- but not delta-opioid receptor agonists is maintained in morphine-tolerant neuropathic rats. Catheline, G; Guilbaud, G; Idänpään-Heikkilä, JJ; Kayser, V, 1996)	1.03
"Morphine treatment modulates a variety of immunological parameters, including tumor necrosis factor-alpha (TNF-alpha) production by activated macrophages in vitro. "	( Effect of morphine on lipopolysaccharide-induced tumor necrosis factor-alpha production in vivo: involvement of the sympathetic nervous system. Bencsics, A; Elenkov, IJ; Vizi, ES, 1997)	2.14
"Morphine-treated animals displayed a marked withdrawal behavior together with beta-adrenoceptor upregulation; nevertheless, these effects were not correlated."	( Effect of yohimbine on the development of morphine dependence in the rat: lack of involvement of cortical beta-adrenoceptor modifications. Alguacil, LF; Ambrosio, E; García-Lecumberri, C; Iglesias, V; Orensanz, L, 1997)	1.28
"The morphine treated animals showed a significant decrease in dynorphin(1-13) levels in the pituitary gland, hypothalamus, hippocampus, striatum, cerebellum, pons, medulla, kidneys, adrenals and spleen, and a significant increase only in the lumbar region of the spinal cord."	( Effect of chronic treatment with morphine, midazolam and both together on dynorphin(1-13) levels in the rat. Rattan, AK; Tejwani, GA, 1997)	1.06
"Morphine treatment of rats (60-70 mg/kg/day, 7 days) reduced delta opioid receptor-mediated inhibition of adenylyl cyclase activity in caudate putamen without any change in regulation by mu receptors. "	( The role of dopaminergic systems in opioid receptor desensitization in nucleus accumbens and caudate putamen of rat after chronic morphine treatment. Cox, BM; Noble, F, 1997)	1.94
"morphine pretreatment (3 nmol, 140 min before testing)."	( The nitric oxide/cyclic GMP system at the supraspinal site is involved in the development of acute morphine antinociceptive tolerance. Bidlack, JM; Hill, KP; Xu, JY, 1998)	1.24
"Morphine-treated females had fewer c-fos cells in mPOA compared to saline-treated females, and the presence of pups accounted for a significant increase in c-fos-expressing neurons, whereas in females not exposed to pups, morphine treatment did not significantly reduce baseline c-fos expression (experiment 1)."	( Opiate disruption of maternal behavior: morphine reduces, and naloxone restores, c-fos activity in the medial preoptic area of lactating rats. Holt, E; Kinsley, CH; Lambert, KG; Polley, D; Stafisso-Sandoz, G, 1998)	1.29
"Morphine-treated animals showed an increase in avoidance acquisition with respect to control group without differences in performance."	( Dose-dependent impairing effects of morphine on avoidance acquisition and performance in male mice. Aguilar, MA; Miñarro, J; Simón, VM, 1998)	1.3
"Morphine-treated rats mounted less vigorous inflammatory responses to the infection and cleared the virus more slowly than placebo-treated rats."	( Morphine alters the immune response to influenza virus infection in Lewis rats. Coussons-Read, ME; Daniels, M; Gilmour, MI, 1998)	2.46
"For morphine treatment, a single injection (100 mg/kg, s.c.) of morphine was followed 4 h later by pellet implantation (75 mg morphine free base)."	( Up-regulation of [3H]DTG but not [3H](+)-pentazocine labeled sigma sites in mouse spinal cord by chronic morphine treatment. Kovács, KJ; Larson, AA, 1998)	1
"Morphine pretreatment modified neither the CPP induced by high doses of cocaine or GBR12783 nor cocaine- or GBR12783-induced stereotypies."	( Sensitization to the rewarding effects of the specific dopamine uptake inhibitor GBR12783. Costentin, J; Duterte-Boucher, D; Le Pen, G, 1998)	1.02
"Morphine treatment was effective in 92% of patients M+, and not very effective in 5%; 67% of patients M- thought that M is efficient but 17% did not know; 76% of patients M+ did not worry about M; 13% worried et 11% did not know."	( [Morphine therapy: evaluation of patient information]. Delfosse, MH; Latour, JF; Ranchere, JY; Saltel, P, 1998)	1.93
"Morphine treatment also significantly attenuated surgery-induced increases in plasma corticosterone concentrations assessed at 5 h after surgery."	( Pre-operative versus postoperative administration of morphine: impact on the neuroendocrine, behavioural, and metastatic-enhancing effects of surgery. Ben-Eliyahu, S; McDonald, JS; Page, GG, 1998)	1.27
"In morphine-pretreated rats (daily administration of subcutaneous morphine: 1, 3, 5, 10, 20 or 40 mg/kg once a day for 4 days), antinociceptive tolerance tested on day 5 by acute morphine (3 mg/kg, i.v.) was manifest in those groups pretreated with the highest doses of morphine (10, 20 or 40 mg/kg)."	( Development of tolerance to the antinociceptive effect of systemic morphine at the lumbar spinal cord level: a c-Fos study in the rat. Besson, JM; Catheline, G; Le Guen, S, 1998)	1.05
"Morphine treatment also induced malondialdehyde and superoxide anions production in leukocyte cells from sensitive mice."	( Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains. Casalinuovo, IA; Di Francesco, P; Di Pierro, D; Garaci, E; Gaziano, R; Lazzarino, G; Tavazzi, B, 1998)	1.31
"All morphine treatments blocked the skin twitch response. "	( Pharmacokinetics and efficacy of epidurally delivered sustained-release encapsulated morphine in dogs. Kohn, FR; Provencher, JC; Rathbun, ML; Yaksh, TL, 1999)	1.09
"Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats."	( Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat. Gerrits, MA; Kitchen, I; Spruijt, BM; Van den Berg, CL; Van Ree, JM, 1999)	2.47
"Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats."	( Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies. Kitchen, I; Spruijt, BM; Van den Berg, CL; Van Ree, JM, 1999)	1.3
"Morphine-treated Jurkat cells also showed a decreased expression of bcl-2 and an enhanced expression of bax."	( Morphine promotes apoptosis in Jurkat cells. Ding, G; Franki, N; Gibbons, N; Kapasi, AA; Reddy, K; Singhal, PC, 1999)	2.47
"The morphine-treated group did not show cross-sensitization to either d-amphetamine (0.1-3 mg/kg) or cocaine (1.0-30 mg/kg); in fact, it showed less cocaine-induced turning than the saline group."	( Sensitization to daily morphine injections in rats with unilateral lesions of the substantia nigra. Easterling, KW; Holtzman, SG; Kimmel, HL; Volpicelli, LA, 1999)	1.09
"Morphine pretreatment potentiated the discriminative stimulus effects of AMPH in three monkeys and either attenuated or did not alter these effects in two monkeys."	( Modulation of the discriminative stimulus effects of d-amphetamine by mu and kappa opioids in squirrel monkeys. Holtzman, SG; Powell, KR, 2000)	1.03
"Morphine treatment during the isolation period enhanced the sucrose intake in non-isolated rats, whereas it decreased sucrose consumption in (partial) isolated rats."	( Morphine attenuates the effects of juvenile isolation in rats. Spruijt, BM; Van den Berg, CL; Van Ree, JM, 2000)	2.47
"Morphine-tolerant mice treated with vehicle+vehicle remained morphine tolerant, whereas this residual morphine tolerance was inhibited by administration of all three NMDA antagonists (each 10 mg/kg)."	( Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice. Danysz, W; Kozela, E; Popik, P, 2000)	1.23
"Morphine treatment also produced significant tolerance in mice (ED(50) shift = 4.5-fold), but no receptor downregulation."	( Role of cAMP-dependent protein kinase (PKA) in opioid agonist-induced mu-opioid receptor downregulation and tolerance in mice. Benedict Gomes, A; Gallagher, A; Shen, J; Stafford, K; Yoburn, BC, 2000)	1.03
"Morphine (20 mg/kg) pretreatment significantly potentiated the ability of naloxone (0.01-0.3 mg/kg) to produce place aversion."	( Pretreatment with morphine potentiates naloxone-conditioned place aversion in mice: effects of NMDA receptor antagonists. Bespalov, AY; Blokhina, EA; Sukhotina, IA, 2000)	1.36
"Morphine treatment was also found to increase the number of calcitonin gene-related peptide-immunoreactive neurons possessing multiple, long branches (i.e."	( Morphine treatment induced calcitonin gene-related peptide and substance P increases in cultured dorsal root ganglion neurons. Kar, S; Ma, W; Quirion, R; Zheng, WH, 2000)	2.47
"Morphine pretreatment further decreased the vocalization threshold in nerve-injured rats and induced threshold reductions in non- and sham-operated rats."	( The development of pain-related behaviour and opioid tolerance after neuropathy-inducing surgery and sham surgery. Christensen, D; Kayser, V, 2000)	1.03
"morphine treatment were observed in brain sections."	( Chronic intrathecal morphine administration produces homologous mu receptor/G-protein desensitization specifically in spinal cord. Childers, SR; Eisenach, JC; Maher, CE; Pan, HL; Xiao, R, 2001)	1.36
"Morphine treatment cessation facilitated an aggressive behaviour of animals during the second day of withdrawal."	( Morphine withdrawal-facilitated aggression is attenuated by morphine-conditioned stimuli. Sukhotina, IA, 2001)	2.47
"Morphine pretreatment failed to show potentiation of both pentobarbital-induced loss of righting reflex and hypothermia in mu-opioid receptor knockout mice, while it significantly potentiated these responses in the wild-type controls."	( Effects of morphine on pentobarbital-induced responses in mu-opioid receptor knockout mice. Ho, IK; Jang, CG; Ko, KH; Loh, HH; Ma, T; Park, Y; Tanaka, S, 2001)	1.42
"Morphine-treated mothers were slower than saline-treated mothers in retrieving all pups into the nest."	( Repeated morphine administration during pregnancy attenuates maternal behavior. Slamberová, R; Szilágyi, B; Vathy, I, 2001)	1.45
"Morphine pretreatment significantly enhanced basal G protein coupling of wild type MOR, which is thought to result from release of CaM."	( Single nucleotide polymorphisms in the human mu opioid receptor gene alter basal G protein coupling and calmodulin binding. Lucas, JL; Quillan, JM; Sadée, W; Wang, D; Winans, K, 2001)	1.03
"Morphine pretreatment did not significantly enhance acute morphine's effects on DA metabolites in any of the brain areas studied in rats of either line."	( Effects of repeated morphine treatment on metabolism of cerebral dopamine and serotonin in alcohol-preferring AA and alcohol-avoiding ANA rats. Ahtee, L; Honkanen, A; Kiianmaa, K; Mikkola, JA; Piepponen, TP, )	1.18
"Morphine treatment of PBMCs decreases IL-2 and IFN gamma and increases IL-4 and IL-5 as a function of morphine concentration. "	( Morphine directs T cells toward T(H2) differentiation. Balasubramanian, S; Barke, RA; Beilman, GJ; Charboneau, R; Melnyk, D; Roy, S; Sumandeep, S; Vatassery, R; Wang, J, 2001)	3.2
"Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine. "	( Temporal factors affecting cocaine-opioid interactions: a cocaine drug discrimination study in rats. Green-Jordan, K; Kantak, KM; Warren, L, 2001)	1.75
"Oral morphine treatment for cancer pain relief is established as central parts of 'WHO Regimen'. "	( [Role of continuous intravenous infusion of morphine in the cancer pain relieving therapy]. Kato, A; Kato, Y, 2001)	1.09
"Morphine treatment is also known to increase circulating levels of glucocorticosteroids, which have been reported to produce genetic damage in vivo and in vitro."	( The role of adrenal corticosteroids in induction of micronuclei by morphine. Couch, DB; Kozlowski, RS; Sawant, SG, 2001)	1.27
"In morphine-pretreated rats, the psychomotor effects of morphine and amphetamine were sensitized."	( A single exposure to morphine induces long-lasting behavioural and neurochemical sensitization in rats. De Vries, TJ; Hogenboom, FA; Schoffelmeer, AN; Vanderschuren, LJ; Wardeh, G, 2001)	1.14
"Morphine pre-treatment potentiates the effects of LPS on endothelial cell viability, and on LPS induction of IL-1beta secretion from 1alpha, 25-dihydroxy-vitamin D3-treated HL-60 human leukemia cells."	( Actions of endotoxin and morphine. Chang, SL; Felix, B; Fiala, M; Jiang, Y, 2001)	1.34
"With Morphine pretreatment, the mean pain scores for the entire 60 min were significantly decreased (P<.05)."	( Scorpion BmK venom induces nociceptive response of rats by plantar injection. Chen, B; Ji, Y; Wang, C, )	0.59
"morphine. Pretreatment with naloxone, an opioid receptor antagonist (1.0 and 4.0 mg/kg, s.c.), failed to reverse the morphine-evoked behavioral response, suggesting that the morphine effect is not mediated through the opioid receptors in the spinal cord."	( Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors. Moriyama, T; Okuda, K; Sakurada, C; Sakurada, S; Sakurada, T; Sugiyama, A; Tan-No, K; Watanabe, C, 2002)	1.35
"Oral morphine is the treatment first recommended for nociceptive pain insufficiently relieved by WHO level I and II analgesics. "	( [New Level III opioids of the World Health Organization]. Laval, G; Mallaret, M; Sang, B; Villard, ML, 2002)	0.83
"Morphine-treated birds (with or without elicited peritonitis) were pretreated with naltrexone, an antagonist of opioid receptors."	( Effect of morphine on thioglycollate-induced peritonitis in chickens. Laskowska, H; Majewski, P; Markowska, M; Skwarlo-Sonta, K; Waloch, M, 2002)	1.44
"Apomorphine pretreatment potentiated the analgesic effect of morphine in a dose-dependent manner both in rats and in mice measured by five different tests (writhing, hot plate, inflamed foot, tail-pinch and tail-flick procedures). "	( Effect of apomorphine on the antinociceptive activity of morphine. Dunai-Kovács, Z; Székely, JI, 1977)	1.25
"Morphine pretreatment produced some increase in the running response to amphetamine and to cocaine."	( Increased running response to morphine in morphine-pretreated mice. Shuster, L; Webster, GW; Yu, G, 1975)	1.26
"In morphine-treated rabbits and mice single doses of doxapram affected neither the time course nor the intensity of the respiratory depression."	( Interactions between morphine and doxapram in the rabbit and mouse. Gregoretti, SM; Pleuvry, BJ, 1977)	1.09
"Morphine pretreatment produced comparable, dose-dependent decreases in response rates in both procedures."	( Fixed-ratio escape and avoidance-escape from naloxone in morphine-dependent monkeys: effects of naloxone dose and morphine pretreatment. Downs, DA; Woods, JH, 1975)	1.22
"Morphine treated animals showed withdrawal symptoms on administration of naloxone 1 mg/kg i.p."	( No psychological dependence after oral administration of morphine to rats. Baldauf, J; Jurna, I; Zenz, M, 1992)	1.25
"Morphine treatment has been shown to suppress several immunologic parameters. "	( Differential effects of morphine and naltrexone on the antibody response in various mouse strains. Adler, MW; Bussiere, JL; Eisenstein, TK; Rogers, TJ, 1992)	2.03
"In morphine-treated pigeons discriminating among naltrexone, saline and morphine, mirfentanil failed to substitute for either training drug; in morphine-abstinent pigeons, mirfentanil reversed responding on the naltrexone key (i.e., reversed withdrawal)."	( Mirfentanil: pharmacological profile of a novel fentanyl derivative with opioid and nonopioid effects. France, CP; Medzihradsky, F; Rice, KC; Seggel, MR; Winger, G; Woods, JH, 1991)	0.8
"Morphine-treated animals displayed neither behavioral estrus nor elevated NE release from the VMH when tested with stimulus males."	( Intracranial dialysis and microinfusion studies suggest that morphine may act in the ventromedial hypothalamus to inhibit female rat sexual behavior. Etgen, AM; van der Plas, J; Vathy, I; Vincent, PA, 1991)	1.24
"Morphine treatment (20 mg/kg for 7 consecutive days) did not affect the density of [3H]dihydroalprenolol ([3H]DHA) binding sites in the cortical membranes of the rat, but during naloxone-precipitated abstinence syndrome the density of these sites increased. "	( Chronic electroconvulsive treatment counteracts cortical beta-adrenoceptor upregulation induced by morphine abstinence. Antkiewicz-Michaluk, L; Michaluk, J; Rokosz-Pelc, A; Vetulani, J, )	1.79
"(-)-Morphine treatment significantly increased antinociception, morphine-induced signs, i-M levels in plasma and CSF, and i-BE, i-ME, and i-LE levels in plasma, but not CSF."	( Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs. Adams, ML; Brase, DA; Dewey, WL; Morris, DL, 1991)	1.06
"morphine in rats pretreated with i.c.v."	( Relationship between regulation of morphine-induced EEG effects and changes in naloxone sensitivity. Paquette, NC; Young, GA, 1991)	1.28
"In morphine-treated animals the increase induced by clonidine was antagonized by prazosin."	( Effect of alpha-adrenoreceptors in the control of spontaneous motility and morphine withdrawal syndrome. Antonelli, T; Bianchi, C; Magri, A; Morari, M, )	0.88
"Morphine treatment had no effect on the 21-hydroxylation reactions or the O-dealkylation of ethylmorphine or codeine."	( A conspicuous down-regulating effect of morphine on essential steroid hydroxylation reactions and certain drug N-demethylations. Ask, B; Rane, A, 1992)	1.27
"In morphine-pretreated rats, dose-effect curves for the opioid antagonists naloxone, naltrexone and diprenorphine shifted to the left of those determined when rats were not morphine-pretreated; whereas those for the mu-opioid agonists morphine and I-methadone and mixed-action opioids nalorphine, nalbuphine, butorphanol, pentazocine and bremazocine were unaltered."	( Acute and chronic morphine administration: effects of mixed-action opioids in rats and squirrel monkeys responding under a schedule of food presentation. Dykstra, LA; Oliveto, AH; Picker, MJ, 1991)	1.13
"Morphine pretreatment did not induce any apparent tolerance to the effect of clonidine and morphine tested 4 h later."	( Interaction between the inhibitory effects of morphine and clonidine on intestinal transit in mice. Wong, CL, 1991)	1.26
"Morphine-treated mice showed similar results to those observed in cocaine or saline treated mice."	( Splenocyte subsets in normal and protein malnourished mice after long-term exposure to cocaine or morphine. Chen, GJ; Huang, DS; Lopez, MC; Watson, RR; Watzl, B, 1991)	1.22
"Morphine and fentanyl treatment, beginning at postnatal day 22, delayed the time of the first ovulation/vaginal opening (VO)."	( Occurrence of sexual maturation in chronic opiate-treated female rats. MacDonald, MC; Wilkinson, M, 1991)	1
"In morphine-treated rats, ir-BNP was shown to circulate mainly as BNP-45, which is identical to a major storage form found in cardiac atrium."	( Concentration and molecular forms of brain natriuretic peptide in rat plasma and spinal cord. Aburaya, M; Kangawa, K; Matsuo, H; Minamino, N; Suzuki, E; Tanaka, K, 1991)	0.8
"Morphine treatment was begun in the hospital and in all cases continued at home."	( [Morphine in the inferior cerebellar cisterna for oncologic pain in the ORL area]. Barzan, L; De Cicco, M; Fracasso, A; Magri, D; Testa, V, 1990)	1.91
"Both morphine and aspirin treatments produced analgesia."	( Amniotic fluid ingestion enhances opioid-mediated but not nonopioid-mediated analgesia. Barton, D; Kristal, MB; Tarapacki, JA, 1990)	0.73
"In morphine-treated (3.2 mg/kg/day) rhesus monkeys discriminating between s.c. "	( Apparent affinity of opioid antagonists in morphine-treated rhesus monkeys discriminating between saline and naltrexone. de Costa, BR; France, CP; Jacobson, AE; Rice, KC; Woods, JH, 1990)	1.16
"Morphine treatment significantly increased the number and density of immuno-labeled nuclei in the ventromedial nucleus, but not in the arcuate nucleus."	( The fos proto-oncogene protein:regulation by morphine in the rat hypothalamus. Chang, SL; Harlan, RE, 1990)	1.26
"Morphine treatment was observed to reduce total dendritic length."	( Perinatal opiate treatment delays growth of cortical dendrites. Hammer, RP; Ricalde, AA, 1990)	1
"Morphine treatment did not alter the temperatures of the contralateral saline-injected paws, indicating that opiate suppression of hyperthermia was not confounded by alterations in systemic body temperature or blood flow."	( Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. Costello, A; Dubner, R; Hargreaves, KM; Joris, J, 1990)	1
"morphine treatment in the mouse."	( Tolerance develops to spinal morphine analgesia but not morphine-induced convulsions. Lutfy, K; Sierra, V; Tortella, FC; Yoburn, BC, 1990)	1.29
"morphine-treated rats was highly significant for groups in withdrawal and for controls (r values, 0.958 and 0.971, respectively)."	( Dependence and withdrawal following intracerebroventricular and systemic morphine administration: functional anatomy and behavior. Adams, RE; Wooten, GF, 1990)	1.23
"Morphine pretreatment combined with formalin injection further increases SPLI, but not significantly higher than either treatment alone."	( Naloxone blocks the formalin-induced increase of substance P in the dorsal horn. Goldstein, BD; McCarson, KE, 1989)	1
"Morphine treatment resulted in a decrease in the maximal excitation produced by both mu and delta selective agonists, [N-MePhe3,D-Pro4]-morphiceptin and [D-Pen2,L-Pen5]-enkephalin."	( Effects of chronic morphine administration on the mu and delta opioid responses in the CA1 region of the rat hippocampus. Chavkin, C; Opheim, KE; Wimpey, TL, 1989)	1.33
"Morphine treatment (25 mg/kg per day) throughout pregnancy resulted in 0% survival of the offspring."	( Effects of prenatal morphine treatment of rats on mortality, bodyweight and analgesic response in the offspring. Eriksson, PS; Rönnbäck, L, 1989)	1.32
"Morphine ingestion treatment was performed with 6 feeding occasions per 24 hr, all experimental animals receiving similar drug doses."	( A method for computer control of morphine ingestion by rats. Eriksson, PS; Rönnbäck, L, 1989)	1.28
"morphine treatment completely prevented morphine-induced changes in hepatic GSH concentrations; however, the morphine response was restored in adrenalectomized mice supplemented with hydrocortisone (2.5 mg/kg)."	( A centrally-mediated effect of morphine to diminish hepatocellular glutathione. James, RC; Roberts, SM; Skoulis, NP, 1987)	1.28
"Morphine pretreatment resulted in the development of acute tolerance to i.c.v."	( Evidence for delta receptor mediation of [D-Pen2,D-Pen5]-enkephalin (DPDPE) analgesia in mice. Heyman, JS; Mosberg, HI; Porreca, F, 1986)	0.99
"Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice."	( Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS. Darban, HR; Prabhala, RH; Smith, TL; Watson, RR; Yahya, MD, 1988)	1.25
"Morphine treatment increased adrenal tyrosine hydroxylase activity to 160% of control."	( Biochemical correlates of morphine withdrawal. 1. Characterization in the adrenal medulla and locus ceruleus. Brown, OM; DiStefano, PS, 1985)	1.29
"More morphine-treated than dezocine-treated patients withdrew from each study because of inadequate pain relief."	( A double-blind comparison of dezocine and morphine in patients with acute renal and ureteral colic. Boyce, WH; Evans, JW; Peters, PC; Warren, MM, 1985)	0.99
"Morphine treatment induced an 8-fold increase in plasma IR-ANF (P less than 0.001) from 68.1 +/- 9.3 (mean +/- S.E.) to 540.5 +/- 139.5 pg/ml and this increase was completely abolished by pretreatment with the opioid antagonist naloxone (P less than 0.001) to 37.9 +/- 2.8 pg/ml."	( The morphine effect on plasma ANF. Cantin, M; Garcia, R; Genest, J; Gutkowska, J; Kuchel, O; Racz, K; Thibault, G, 1986)	1.55
"In morphine-pretreated arthritic animals, the analgesic effect of low doses of naloxone was significantly attenuated."	( Cross-tolerance between analgesic low doses of morphine and naloxone in arthritic rats. Guilbaud, G; Kayser, V, 1987)	1.04
"Morphine pretreatment partially inhibited the effect of CMI irrespective of the morphine pretreatment dose, but reduction of morphine activity by CMI was non-significant."	( Study of the clomipramine-morphine interaction in the forced swimming test in mice. Eschalier, A; Fialip, J; Makambila, MC; Varoquaux, O, 1987)	1.29
"morphine after i.p. pretreatment with saline, glucose (5 g/kg) or fructose (5 g/kg) in the mouse tail-flick test indicated that fructose was more potent than glucose in antagonizing antinociception after either route or morphine administration."	( Antagonism of antinociception in mice by glucose and fructose: comparison of subcutaneous and intrathecal morphine. Brase, DA; Dewey, WL; Lux, F, 1988)	1.21
"Morphine-tolerant mice treated with met-enkephalin or DADL intracerebroventricularly (ICV) showed marked reduction of the pupillary effect of the endopioids."	( Opioid mydriasis: cross-tolerance between morphine and enkephalins. Ben-Am, M; Korczyn, AD, 1986)	1.26
"Morphine pretreatment did not significantly affect the apparent pA2 of apomorphinehaloperidol for climbing behavior suggesting that the affinity of the dopamine receptor was not altered."	( Further evidence that a single dose of an opiate can increase dopamine receptor sensitivity in mice. Martin, JR; Takemori, AE, 1987)	0.99
"Morphine treatment (15 mg X kg-1, i.p.) significantly protects against the development of this pathology."	( Endogenous opioids are not involved in the pathology induced by hyperbaric oxygen treatment. Carmody, J; Jamieson, D, 1987)	0.99
"Morphine treatment alone did not influence significantly the basal PRL plasma concentration."	( The effect of magnesium aspartate, xylazine and morphine on the immobilization-induced increase in the levels of prolactin in turkey plasma. Ali, BH; el Halawani, ME; Silsby, JL, 1987)	1.25
"Morphine pretreatment also caused a dose-dependent increase in plasma Adriamycin, as measured by total plasma fluorescence."	( A novel acute toxicity resulting from the administration of morphine and adriamycin to mice. Hurwitz, A; Innis, JD; Meyer, M, 1987)	1.24
"Morphine-treated rats exhibited decreased gastric acid secretion, increased gastric mucus synthesis and a higher mean ulcer index but only the reduced gastric acid output was significantly prevented by atropine."	( Effects of morphine, hypoxaemia and hypercapnia on the rat stomach. Dai, S; Ho, MM; Ogle, CW, 1986)	1.38
"Morphine treatment was associated with an immediate (15-30 min) inhibition of gastric and colonic spiking activity and intestinal migrating myoelectric complex lasting 6 to 8 hr, followed by a partial recovery of gastric spiking activity while a permanent disorganized motility pattern persisted on the intestine."	( Effects of centrally administered naloxone on gastrointestinal myoelectrical activity in morphine-dependent rats. Bueno, L; Primi, MP, 1987)	1.22
"Morphine-treated mice, warmed to reverse hypothermia, still had higher plasma and liver BSP levels."	( Opioid effects on hepatic disposition of dyes in mice. Ben-Zvi, Z; Fischer, HR; Hurwitz, A; Innis, JD; Ronsse, S, 1985)	0.99
"Morphine-treated rams showed normal LH responses to injections of LH-releasing hormone (LHRH) indicating that the site of opiate inhibition was on hypothalamic LHRH secretion rather than on pituitary LH release."	( Endogenous opioids and the control of seasonal LH secretion in Soay rams. Ebling, FJ; Lincoln, GA, 1985)	0.99
"Treatment with morphine (2 and 4 mg/kg) or CBD (30 mg/kg) induced a significant antinociceptive effect on evoked pain."	( Cannabidiol enhances the antinociceptive effects of morphine and attenuates opioid-induced tolerance in the chronic constriction injury model. Chichorro, JG; Crippa, JAS; Cunha, JMD; Ferreira, MV; Gasparin, AT; Genaro, K; Jesus, CHA; Rosa, ES, 2022)	1.31
"A treatment with morphine, counteracting the pain, prevents the development of anxio-depressive disorders and reduces neuroinflammation."	( Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine. Amodeo, G; Baciarello, M; Bignami, EG; D'Agnelli, S; Franchi, S; Galimberti, G; Sacerdote, P, 2023)	1.44
"Treatment with morphine did not alter the expressions of cold sensitive TREK-1, TRAAK and TRPM8 in DRGs."	( Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling. Altier, C; Basso, L; Defaye, M; Flynn, R; Hassan, A; Iftinca, M; Kwok, C; Ramachandran, R; Roland, C; Trang, T, 2020)	1.33
"Pretreatment with morphine augmented p38 phosphorylation, and the increased phospho-p38/p38 ratio was preserved even in the presence of t-BHP."	( Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells. Hejnova, L; Karlovska, I; Novotny, J; Skrabalova, J, 2018)	1.12
"Pretreatment with morphine did not affect the neurobehavioral response to chronic RS, but reverted the GSH and Hsp70 expression."	( Differential modulatory effects of morphine on acute and chronic stress induced neurobehavioral and cellular markers in rats. Gulati, K; Joshi, JC; Ray, A, 2014)	1
"Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H2O2 in effluate before doxorubicin infusion (p < 0.05)."	( Morphine enhances doxorubicin-induced cardiotoxicity in the rat. Fossan, KO; Hole, LD; Larsen, TH; Limé, F; Schjøtt, J, 2014)	2.17
"Pretreatment with morphine (1 and 5 mg/kg) and L-arginine (500 mg/kg) attenuated the RS effects on EPM activity and brain NOx, whereas, Hsp70 levels were further augmented."	( Effects of morphine on stress induced anxiety in rats: role of nitric oxide and Hsp70. Gulati, K; Joshi, JC; Ray, A, 2015)	1.13
"Treatment with morphine at 3 or 10 mg/kg significantly improved limb-use and weight-bearing scores and reduced the number of spontaneous flinches in rats. "	( Protease-activated receptor 2 antagonist potentiates analgesic effects of systemic morphine in a rat model of bone cancer pain. Bao, Y; Du, M; Gao, Y; Hou, W; Hua, B; Kong, X; Yang, L; Zheng, H, )	0.71
"Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. "	( Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats. Adams, NJ; Barrett, LA; Beausoleil, NJ; Chambers, JP; Farnworth, MJ; Hekman, M; Stafford, KJ; Thomas, DG; Waran, NK; Weidgraaf, K, 2015)	0.75
"Treatment with morphine leads to enrichment of a side population fraction in MCF-7 cells and the CD44+/CD24(-/low) population in BT549 cells."	( Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer. Gao, P; Guan, Z; Han, QN; Li, JL; Li, TT; Liu, Q; Niu, DG; Peng, F; Wang, KL; Wen, QP; Xu, F; Zhang, W; Zhang, Y; Zhao, HD; Zheng, FM, 2015)	2.2
"Treatment with morphine in HT-29 cells did not change AQP3 expression."	( Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion. Fueki, A; Haga, Y; Hayakawa, A; Ikarashi, N; Kon, R; Kusunoki, Y; Machida, Y; Ochiai, W; Sugiyama, K; Tajima, M, 2015)	2.2
"Pre-treatment with morphine (2, 6, 12 μg/paw) inhibited jararhagin-induced mechanical hyperagesia."	( Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice. Baldo, C; Calixto-Campos, C; Casagrande, R; Clissa, PB; Ferraz, CR; Manchope, MF; Verri, WA, 2015)	0.74
"Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin."	( Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone. Aminian, A; Asadi Amoli, F; Dehpour, AR; Ejtemaei Mehr, S; Javadi, S; Moghaddas, P; Rahimian, R, 2016)	1.04
"Mice treated with morphine had reduced wound closure and higher wound superoxide ions concentrations than control mice. "	( Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice. Chang, PJ; Huang, CC; Huang, YS; Lam, CF; Lin, MW; Liu, YC; Sung, YH; Tsai, YC, 2008)	0.98
"Treatment with morphine was associated with a higher rate of side effects."	( Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Agarwal, S; Clark, MR; Haythornthwaite, JA; Klick, B; Max, MB; Raja, SN; Tella, PK; Wu, CL, 2008)	2.13
"The treatment with morphine increases PKCgamma and Vps34 levels."	( Direct evidence for the up-regulation of Vps34 regulated by PKCgamma during short-term treatment with morphine. Katsura, M; Kurokawa, K; Ohkuma, S; Shibasaki, M, 2009)	0.89
"Pretreatment with morphine suppressed the glutamate increase."	( [Effect of a simple morphine system injection in some aminoacids in the anterior cingulate cortex during acute pain]. Hernández, L; Páez, X; Quiñones, B; Silva, E, 2008)	0.99
"The treatment with morphine increased alpha(2)/delta subunit expression in the frontal cortex and the limbic forebrain of mice showing rewarding effect and sensitization to hyperlocomotion by morphine."	( Role of alpha2/delta subunit in the development of morphine-induced rewarding effect and behavioral sensitization. Kurokawa, K; Ohkuma, S; Shibasaki, M, 2009)	0.92
"Treatment with morphine for a period of six days resulted in a persistent hyperalgesia that resolved many days after termination of drug administration."	( Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity. King, T; Lian, B; Ossipov, MH; Porreca, F; Vera-Portocarrero, L, 2010)	0.7
"Pretreatment with morphine did not induce an elevation of LDH activity or of lipid peroxidation compared to controls."	( Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry. Aricò, M; Genitori, L; Giovannini, MG; Guerrini, R; la Marca, G; Malvagia, S; Massimino, M; Sardi, I, 2011)	0.92
"Rats treated with morphine (twice daily, 6 days, 2.5-10 mg/kg, subcutaneously, s.c.) or saline were group-housed in two different conditions."	( Social influences on morphine sensitization in adolescent rats. Eitan, S; Hofford, RS; Schul, DL; Wellman, PJ, 2012)	1.02
"Pretreatment with morphine (1 and 5mg/kg), attenuated the restraint stress induced anxiogenic response in a dose related manner."	( Pharmacological evidence for the role of nitric oxide in the modulation of stress-induced anxiety by morphine in rats. Anand, R; Gulati, K; Ray, A, 2012)	0.92
"Treatment with morphine (1mg/kg, s.c.) at one day after the surgery showed a significant anti-allodynic effect."	( Involvement of inflammation in severe post-operative pain demonstrated by pre-surgical and post-surgical treatment with piroxicam and ketorolac. Fujita, I; Kita, Y; Okumura, T; Sakakibara, A, 2012)	0.72
"Treatment with morphine reduced locomotion and rearing similarly in both genotypes but reduced total grooming only in MUT mice."	( Behavioural and anatomical characterization of mutant mice with targeted deletion of D1 dopamine receptor-expressing cells: response to acute morphine. Babovic, D; Drago, J; Gantois, I; Goto, S; Jiang, L; Lawrence, AJ; Schütz, G; Waddington, JL, 2013)	0.93
"treatment with morphine, the intensive PLCgamma1-IR was detected in the cell surface of the positive cells."	( Direct evidence for the activation of phospholipase C gamma 1 by in vivo treatment with morphine in the mouse periaqueductal gray matter. Aoki, T; Funahashi, H; Narita, M; Ohnishi, O; Shioda, S; Suzuki, M; Suzuki, T; Yajima, Y, 2003)	0.88
"Pre-treatment with morphine inhibited the distension-induced visceromotor response, i.e."	( Telemetric animal model to evaluate visceral pain in the freely moving rat. Coulie, B; Meulemans, AL; Nijsen, MJ; Ongenae, NG, 2003)	0.64
"Treatment of morphine-dependent rats with Nomega-nitro-l-arginine methyl ester also enhanced oxytocin secretion during naloxone-precipitated withdrawal."	( The role of nitric oxide in morphine dependence and withdrawal excitation of rat oxytocin neurons. Blackburn-Munro, GJ; Brown, CH; Bull, PM; Delgado-Cohen, H; Ludwig, M; Russell, JA, 2003)	0.97
"Treatment with morphine reduced effects of noxious stimulation and appears to be an effective analgesic."	( Novel object test: examining nociception and fear in the rainbow trout. Braithwaite, VA; Gentle, MJ; Sneddon, LU, 2003)	0.66
"Pretreatment with morphine (3-12 microg paw(-1)) also dose-dependently inhibited the IL-18-induced hypernociception."	( Interleukin-18 induces mechanical hypernociception in rats via endothelin acting on ETB receptors in a morphine-sensitive manner. Cunha, FQ; Cunha, TM; Ferreira, SH; Liew, FY; Schivo, IR; Verri, WA, 2004)	0.86
"Pretreatment with morphine or deltorphine (but not with U-50,488H) enhanced leukocyte migration to L15 and S in each species, while it inhibited migration of mouse and fish (but not frog) leukocytes to ZAS, phenomena reversed by specific antagonists of mu and delta opioid receptors (CTOP or naltrindole, respectively)."	( Differential migratory properties of mouse, fish, and frog leukocytes treated with agonists of opioid receptors. Chadzinska, M; Plytycz, B, 2004)	0.65
": Pretreatment with morphine induces delayed cardioprotection in mice. "	( Inducible nitric oxide synthase mediates delayed cardioprotection induced by morphine in vivo: evidence from pharmacologic inhibition and gene-knockout mice. Jiang, X; Nakajima, Y; Sato, S; Shi, E, 2004)	0.88
"Pretreatment with morphine blunted changes in the HVA/DA ratio induced by another morphine challenge, but it had no effect on the DOPAC/DA ratio within the caudate putamen."	( A single exposure to morphine induces long-lasting hyporeactivity of rat caudate putamen dopaminergic nerve terminals. Ali, SF; Macedo, TR; Pereira, FC; Ribeiro, CF; Santos, SD, 2004)	0.97
"Treatment with morphine (1 mg/kg) induced a significant increase in exploratory behavior in an unfamiliar environment in rats."	( Alterations in opioid system of the rat brain after cat odor exposure. Areda, T; Asser, T; Karis, A; Kõks, S; Philips, MA; Vasar, E, 2005)	0.67
"Pretreatment with morphine 30 min before pulp exposure dose-dependently (2.5, 5, and 10 mg/kg subcutaneously) reduced Fos expression in subnucleus caudalis whereas pretreatment with ibuprofen (10-100 mg/kg subcutaneously) did not significantly affect Fos expression."	( Effects of pre-emptive morphine, ibuprofen or local anesthetic on fos expression in the spinal trigeminal nucleus following tooth pulp exposure in the rat. Erickson, TE; Gebhart, GF; Johnson, WT; Law, AS; Locher-Claus, MT, 2005)	0.96
"Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin."	( The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Cabot, PJ; Monteith, GR; Roberts-Thomson, SJ; Vetter, I; Wyse, BD, 2006)	0.97
"Treatment with morphine increased the numbers of FRAP-positive terminals, and this was prevented by naloxone."	( Morphine acts via mu-opioid receptors to enhance spinal regeneration and synaptic reconstruction of primary afferent fibers injured by sciatic nerve crush. Chen, SJ; Nie, JH; Wu, W; Zeng, YS; Zhang, W, 2007)	2.12
"Mice treated with morphine and injected intracerebroventricularly with DNAzyme did not show preference to the morphine-trained side."	( The extracellular signal-regulated kinase signaling pathway is involved in the modulation of morphine-induced reward by mPer1. Jiang, Z; Liu, Y; Wan, C; Wang, Y; Wang, Z; Zhou, W, 2007)	0.88
"Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later."	( The impact of morphine after a spinal cord injury. Bopp, AC; Ferguson, AR; Grau, JW; Hook, MA; Huie, JR; Liu, GT; Washburn, SN, 2007)	1.02
"Pretreatment with morphine (5 mg/kg, s.c.) did not influence the effects of VIP on net water flux and on mucosal cyclic AMP content."	( Influence of vasoactive intestinal polypeptide on net water flux and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum. Beubler, E, 1980)	0.58
"4 Pretreatment with morphine (10 mg/kg, s.c.) reduced the effect of PGE1 on net water flux and completely inhibited its effect on the mucosal cyclic AMP content."	( Inhibition by morphine of prostaglandin E1-stimulated secretion and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum in vivo. Beubler, E; Lembeck, F, 1980)	0.94
"Treatment with morphine (1 or 5 mg/kg), but not pancuronium (0.3 mg/kg), attenuated the plasma beta-END-LI response to mechanical ventilation, suggesting that a subconscious phenomenon, perhaps related to pain, was partially responsible for the profound release of pituitary beta-END-LI associated with artificial respiration."	( Anesthesia and stimulation of pituitary beta-endorphin release in rats. Maiewski, S; Mueller, GP; Muldoon, S, 1984)	0.61
"Pretreatment with morphine did not affect the inhibitory effect of nalbuphine, and the antagonistic potency of naloxone against nalbuphine was only marginally enhanced."	( The effects of morphine and nalbuphine on intestinal transit in mice. Wong, CL, 1984)	0.94
"Pretreatment with morphine 2.0 mg/kg subcutaneously did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later."	( Increased naloxone potency induced by pretreatment with morphine and nalbuphine in mice. Wai, MK; Wong, CL, )	0.7
"Pretreatment with morphine did not reduce the release of TSH induced by exogenous thyrotrophin-releasing hormone (TRH) but enhanced it."	( Effect of morphine on the release of thyroid-stimulating hormone stimulated by exposure to cold, thyroidectomy and the administration of thyrotrophin releasing hormone in male rats. Kato, R; Muraki, T; Nakadate, T; Tokunaga, Y, 1980)	0.99
"Treatment with morphine or the analog caused significantly reduced alternation, i.e., arms were entered with equal probability."	( Y-maze behavior in the mouse after morphine or an enkephalin analog. Katz, RJ; Schmaltz, K, 1981)	0.88
"A pretreatment with morphine (100 micrograms/kg, I.C.V.) completely prevents the central hypotensive effect of clonidine, whereas the bradycardia is only weakly influenced."	( [Morphine antagonizes the central hypotensive effect of clonidine in the anesthetized cat]. Bloch, R; Bousquet, P; Feldman, J; Schwartz, J, 1982)	1.49
"Mice treated with morphine (100 mg/kg SC) and 3 hr later with naloxone (30 mg/kg) developed an acute abstinence syndrome characterized by escape attempts (rearing, wall-climbing, jumping) and unconditioned motor (head-shaking, jerking) and visceral signs. "	( Cortical spreading depression blocks naloxone-induced escape behaviour in morphine pretreated mice. Bures, J; Peréz-Saad, H, 1983)	0.83
"Pretreatment with morphine, pentazocine and scopolamine at motor stimulant doses before each training session did not affect acquisition of brightness discrimination."	( Acquisition of brightness discrimination in the rat is impaired by opiates with psychotomimetic properties. Franklin, SR; Tang, AH, 1983)	0.59
"Treatment with morphine decreased the dorsal potential and blocked the increase in amplitude induced by noxious by noxious stimuli."	( Correlates of nociception and antinociception in dorsal root potentials in the rat. Wilcox, GL, 1982)	0.6
"Mice treated with morphine (intracerebroventricularly, retrobulbarly or intraperitoneally) demonstrated dose related bilateral mydriasis. "	( Central and peripheral components of morphine mydriasis in mice. Korczyn, AD; Maor, D, 1982)	0.87
"Treatment with morphine decreased serum LH and testosterone concentrations and reduced secondary sex organ weights."	( Effects of morphine sulphate on pituitary-testicular morphology of rats. Crook, D; Heywood, R; James, RW, 1980)	0.99
"The treatment of morphine induced H, A, and M seems to be to discontinue morphine administration and to initiate therapy with other opioids (fentanyl, sufentanyl, methadone or ketobemidone)."	( [Morphine-induced hyperalgesia, allodynia and myoclonus--new side-effects of morphine?]. Jacobsen, LS; Jensen, NH; Olsen, AK; Sjøgren, P, 1995)	1.53
"Rats treated with morphine chronically exhibited not only tolerance to the analgesic effect but also tolerance to the exacerbating action."	( kappa-Opioid receptor agonist protects against ischemic reduction of 2-deoxyglucose uptake in morphine-tolerant rats. Shibata, S; Tominaga, K; Watanabe, S, 1995)	0.83
"Treatment with morphine decreased capsaicin-induced responses, and naloxone reversed the inhibitory effect."	( Morphine modulates contractile responses and neurokinin A-LI release elicited by electrical field stimulation or capsaicin in a guinea pig bronchial-tube preparation. Andersson, RG; Lindström, EG, 1995)	2.07
"Pretreatment with morphine (I.V.) blocked the effects of CCK in a naloxone-reversible manner."	( Presynaptic actions of morphine: blockade of cholecystokinin-induced noradrenaline release in the rat supraoptic nucleus. Guevara-Guzman, R; Kendrick, K; Leng, G; Luckman, SM; Onaka, T; Ueta, Y, 1995)	0.93
"Pretreatment with morphine (3 nmol, -140 min) produced acute antinociceptive tolerance as demonstrated by a 45-fold rightward shift of the morphine dose-response curve."	( Preventing morphine antinociceptive tolerance by irreversible mu opioid antagonists before the onset of their antagonism. Archer, S; Bidlack, JM; Jiang, Q; Sebastian, A; Seyed-Mozaffari, A, 1995)	1
"Pretreatment with morphine (3.0 mg/kg, SC) resulted in a 70-fold increase in sensitivity to the response rate decreasing effect of naltrexone compared with saline pretreatment."	( Naloxone pretreatment blocks acute morphine-induced sensitization to naltrexone. Holtzman, S; White-Gbadebo, D, 1994)	0.89
"Treatment with morphine resulted in a decrease in MAP and an increase in heart rate."	( Effects of opioid agonists and opioid antagonists in endotoxic shock in rats. Tseng, CS; Tso, HS, 1993)	0.63
"Treatment with morphine for 5 days increased calbindin-ir in the striatal matrix, and induced intense calbindin-ir in the patch compartment."	( Chronic morphine increases calbindin D28k in rat striatum: possible NMDA receptor involvement. Garcia, MM; Harlan, RE, 1993)	1.06
"Upon treatment with morphine, no major effects on the sequential structure of social behavior were observed: pinning and boxing/wrestling appeared more associated with following/chasing, and the negative association between pinning and boxing/wrestling on the one hand and social exploration on the other was enhanced."	( Sequential analysis of social play behavior in juvenile rats: effects of morphine. Hol, T; Niesink, RJ; Spruijt, BM; Van Ree, JM; Vanderschuren, LJ, 1995)	0.84
"Pretreatment with morphine for 10 days by continuous subcutaneous infusion (15 mg/kg/day) reduced the ED25 value of NTX from 28.2 to 0.002 +/- 1.48 mg/kg."	( Intracranial self-stimulation in rats: sensitization to an opioid antagonist following acute or chronic treatment with mu opioid agonists. Easterling, KW; Holtzman, SG, 1997)	0.62
"Pretreatment of morphine-dependent rats with an intrathecal injection of 100 nmol of the neurokinin-1 receptor antagonist CP-99994 significantly inhibited the magnitude and shortened the duration of the pressor response to naloxone."	( Effect of intrathecal pretreatment with the neurokinin receptor antagonist CP-99994 on the expression of naloxone-precipitated morphine withdrawal symptoms. Buccafusco, JJ; Shuster, LC, 1997)	0.84
"Pretreatment with morphine alone (10 mg/kg s.c., two times a day during 4 days) induced a complete tolerance to the antinociceptive effect of acute morphine (0.1-1.0 mg/kg i.v.)."	( Prevention of tolerance to the antinociceptive effects of systemic morphine by a selective cholecystokinin-B receptor antagonist in a rat model of peripheral neuropathy. Guilbaud, G; Idänpään-Heikkilä, JJ; Kayser, V, 1997)	0.86
"We treated morphine-induced emesis in ferrets with electroacupuncture (EA) for five minutes at the acupuncture point Neiguan (P6) using two different frequencies of stimulation: 1.0 Hz and 5.0 Hz (n = 5 ferrets per group). "	( Electroacupuncture reduces morphine-induced emesis in ferrets: a pilot study. Berman, B; Lao, L; Wong, RH; Wynn, RL, 1995)	0.98
"Pretreatment with morphine (2.5-30 mg/kg, SC) led to a dose-dependent increase in time spent in the morphine-paired compartment."	( Effects of test conditions on the outcome of place conditioning with morphine and naltrexone in mice. Balster, RL; Beardsley, PM; Bespalov, AY; Bowen, SE; Tokarz, ME, 1999)	0.86
"Pretreatment with morphine increased NEP activities (9.86 +/- 1.98 vs."	( Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction. Chang, H; Hung, CR; Tseng, YZ; Wang, TL, 1998)	2.07
"Pretreatment with morphine (3 and 10 mg/kg, i.p.) significantly reduced the induction of Fos-IR neurons at the superficial layers of the ipsilateral SpVc in a dose-dependent manner, and its effect was antagonized by the subsequent treatment of naloxone (2 mg/kg, i.p.)."	( Effects of morphine on the distribution of Fos protein in the trigeminal subnucleus caudalis neurons during experimental tooth movement of the rat molar. Aihara, Y; Hanada, K; Maeda, T; Wakisaka, S, 1999)	1.02
"Treatment with morphine lowered the [32P]-incorporation in HMG I and HMGI-C proteins and the level of the HMG I/Y transcript."	( Morphine treatment affects the regulation of high mobility group I-type chromosomal phosphoproteins in C6 glioma cells. Angelova, A; Chakalova, L; Chakarov, S; Ganev, V; Tencheva, Z, 2000)	2.09
"In untreated mice, morphine, fentanyl, clonidine, oxymetazoline, desipramine and lidocaine, but not MK801, produced dose-related antinociception when tested using a 55 degrees C water tail-flick test."	( Pharmacologic reversal of pertussis toxin-induced thermal allodynia in mice. Shannon, HE; Womer, DE, 2000)	0.63
"Pretreatment with morphine significantly suppressed the machine milking-induced increase of cortisol in blood plasma as compared with controls."	( Cortisol and ACTH release in dairy cows in response to machine milking after pretreatment with morphine and naloxone. Kraetzl, WD; Schams, D; Tancin, V, 2000)	0.85
"Treatment with morphine (10 mg/kg, subcutaneously (s.c.)) inhibited gastrointestinal transit and hyperlocomotion."	( Effects of fluvoxamine on morphine-induced inhibition of gastrointestinal transit, antinociception and hyperlocomotion in mice. Aoki, T; Hirano, M; Ise, Y; Katayama, S; Narita, M; Suzuki, T, 2001)	0.95
"Pretreatment with morphine (300 microg x kg(-1), i.v.) 10-min before ischemia and reperfusion mimicked the protection produced by PC."	( Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine. Dun, Y; Hao, YB; Wu, YX; Yang, SP; Zhang, Y, 2001)	0.63
"treatment with morphine or heroin decreased mu opioid receptor activation of G-proteins in specific brain regions."	( Chronic intrathecal morphine administration produces homologous mu receptor/G-protein desensitization specifically in spinal cord. Childers, SR; Eisenach, JC; Maher, CE; Pan, HL; Xiao, R, 2001)	0.97
"Pretreatment with morphine-like agonists potentiates the behavioral effects of opioid antagonists, possibly reflecting a state of acute physical dependence. "	( Acute opioid pretreatment potentiates naltrexone-induced drinking suppression in water-deprived rats. Holtzman, SG; White, DA, 2001)	0.64
"Pretreatment with morphine caused a dose-related reduction in emesis induced by a single challenge to a motion stimulus."	( Opioid receptor involvement in the adaptation to motion sickness in Suncus murinus. Javid, FA; Naylor, RJ, 2001)	0.63
"Treatment with morphine increases [14C]-inulin permeability of an in vitro microvascular endothelial cell barrier, and decreases endothelial cell viability."	( Actions of endotoxin and morphine. Chang, SL; Felix, B; Fiala, M; Jiang, Y, 2001)	0.95
"Pretreatment with morphine (2 mg/kg) attenuated, in a naloxone-reversible manner, the nociceptive behaviour observed following intradental application of capsaicin."	( Nociceptive behaviour induced by dental application of irritants to rat incisors: a new model for tooth inflammatory pain. Chidiac, JJ; Hawwa, NN; Jabbur, SJ; Jurjus, AR; Massaad, CA; Rifai, K; Saadé, NE, 2002)	0.64
"Pretreatment with morphine greatly reduces Fos-LI produced in the dorsal paratrigeminal area (dPa5), ventrolateral pole of the subnucleus interpolaris/caudalis (Vi/Vc-vl) transition region, and laminae I-II at the subnucleus caudalis/upper cervical cord junction (Vc/C2) suggesting a role for these areas in processing pain signals from the TMJ region."	( Vagotomy prevents morphine-induced reduction in Fos-like immunoreactivity in trigeminal spinal nucleus produced after TMJ injury in a sex-dependent manner. Bereiter, DA; Bereiter, DF; Ramos, M, 2002)	0.97
"Posttreatment with morphine also resulted in comparable suppression of the phase 2 response (ED50 = 0.2 micrograms [95% CI = 0.1-0.3])."	( Comparison of the antinociceptive effects of pre- and posttreatment with intrathecal morphine and MK801, an NMDA antagonist, on the formalin test in the rat. Yaksh, TL; Yamamoto, T, 1992)	0.83
"Pretreatment with morphine or BW443C did not influence the acid responses to i.v."	( Modulation by peripheral opioids of basal and distension-stimulated gastric acid secretion in the rat. Barrachina, MD; Esplugues, J; Esplugues, JV, 1992)	0.61
"AZT-treatment, morphine-treatment, AZT plus morphine treatment and AZT plus methadone treatment strongly depressed the phagocytic physiological activity of Polymorphonuclear leukocytes (PMNs)."	( Immunological consequences of zidovudine treatment in control and morphine or methadone treated mice. Bacosi, A; Caronna, A; Di Carlo, S; Pacifici, R; Pichini, S; Zuccaro, P, 1992)	0.86
"Pretreatment with morphine resulted in cocaine-induced seizures of 20%, 80% and 100%, respectively (p less than or equal to 0.05 with cocaine 35 and 50 mg/kg)."	( The effect of morphine and naloxone on cocaine toxicity. Albertson, TE; Derlet, RW; Tharratt, RS; Tseng, CC, 1992)	0.97
"Pretreatment of morphine-dependent rats with the same dose of daY8Ra also significantly attenuated (p less than 0.001) the abstinence signs subsequently precipitated by 10 micrograms naloxone ICV."	( Analog of neuropeptide FF attenuates morphine abstinence syndrome. Arcangeli, KR; Hammond, MV; Lake, JR; Leyva, JE; Ludgate, K; Malin, DH; Moore, GM; Payza, K; Rogillio, RB, )	0.74
"Pretreatment with morphine also abolished the morphine-induced increase in Cai of isolated myocytes."	( Morphine and (D-Ala2, NMe-Phe4, Gly-ol)-enkephalin increase the intracellular free calcium in isolated rat myocytes--effect of naloxone or pretreatment with morphine. Huang, XD; Wong, TM, 1991)	2.05
"Treatment with morphine or beta-endorphin associated with each immobilization session for 3 days produced a response to 5-MeODMT higher than that of animals subjected to immobilization only."	( Opioid involvement in the adaptive change of 5-HT1 receptors induced by chronic restraint. Cancela, L; Molina, VA; Volosin, M, 1990)	0.62
"Rats treated with morphine showed withdrawal signs such as hyperirritability, salivation, diarrhea, and weight loss."	( Physical dependence potential of an enkephalin analog, EK-399, in rats. Nishida, N, 1990)	0.6
"Pretreatment with morphine at a dose of 10 mg/kg (i.v.) significantly enhanced the release of 5-HT."	( Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit. Imai, Y; Inoki, R; Shibutani, T; Yonehara, N, 1990)	0.6
"Pretreatment with morphine and naloxone prevented the long-term blockade by SP."	( Substance P-induced long-term blockade of spinal adrenergic analgesia: reversal by morphine and naloxone. Nance, PW; Sawynok, J, 1987)	0.82
"Treatment with morphine inhibited the late response without affecting the initial response."	( Two types of gastric excitatory responses to stimulation of the vagal trunk in cats: efferent and afferent responses. Fujiwara, M; Kurahashi, K; Okamoto, T; Tsubomura, T, 1988)	0.61
"Pretreatment of morphine for 5 min significantly augmented the subsequent BK responses for 30 min or more."	( Facilitatory effects of opioids on the discharges of visceral nociceptors. Kumazawa, T; Minagawa, M; Mizumura, K; Sato, J, 1989)	0.61
"Pretreatment with morphine or DADLE did not alter the LH response to GnRH (100 micrograms) stimulation, indicating a hypothalamic site of action for the opioid inhibition of LH release."	( Opioid effects on plasma concentrations of luteinizing hormone and prolactin in the adult male rhesus monkey. Almirez, RG; Gilbeau, PM; Holaday, JW; Smith, CG, 1985)	0.59
"A pretreatment with morphine inhibited the stress-induced reduction in the hypothalamic NE and DA concentrations, and induced a significant increase in the DA concentration."	( Effects of morphine on hypothalamic corticotropin-releasing factor (CRF), norepinephrine and dopamine in non-stressed and stressed rats. Hashimoto, K; Ota, Z; Suemaru, S, 1985)	0.97
"Pretreatment with morphine (2.5 mg/kg), a mu agonist, or ethylketocyclazocine (EKC: 2.5 mg/kg), a kappa agonist, potentiated hypothermia induced by high dose of PCP."	( Involvement of opioid receptors in hypo- and hyperthermic effects induced by phencyclidine in mice. Hiramatsu, M; Kameyama, T; Nabeshima, T, 1986)	0.59
"Rats treated with morphine exhibited body weight loss upon the naloxone injection."	( Effect of opioid agonist-antagonist interaction on morphine dependence in rats. Fukagawa, Y; Suzuki, T; Yanaura, S; Yoshii, T, 1988)	0.85
"Pretreatment with morphine had little or no effect on MBP or HR responses to AII."	( Attenuation by naloxone of the pressor effects of angiotensin II in conscious cynomolgus monkeys. Kirby, DA; Spealman, RD, 1988)	0.6
"Pretreatment with morphine (20 mg/kg) reduced by 80% the dose of Adriamycin required to induce a 30% mortality at 30 min post-Adriamycin administration."	( A novel acute toxicity resulting from the administration of morphine and adriamycin to mice. Hurwitz, A; Innis, JD; Meyer, M, 1987)	0.84
"Treatment with morphine did not cause substantial pain relief in a substantial number of patients."	( Pain assessment by patients and nurses in the early phase of acute myocardial infarction. Bondestam, E; Gaston Johansson, F; Herlitz, J; Holmberg, S; Hovgren, K; Jern, S, 1987)	0.61
"Pretreatment with morphine (1-10 mg/kg s.c.) 10 min before kainic acid administration significantly increased the number of spikes in the EEG in a dose-dependent manner."	( Potentiating effect of morphine on seizures induced by kainic acid in rats. An electroencephalographic study. Benedek, G; Joó, F; Lelkes, Z; Sztriha, L, 1986)	0.91
"Treatment with morphine consistently elevated serum prolactin concentrations (greater than 100%) in castrated rats of all ages, regardless of the time elapsed after gonadectomy."	( A 'window of time' during which testosterone determines the opiatergic control of LH release in the adult male rat. Almeida, OF; Herz, A; Nikolarakis, KE; Schulz, R, 1987)	0.61
"Pretreatment with morphine enhanced licking behaviour and, in addition, produced some gnawing behaviour, a sign which is seen after a larger dose of apomorphine alone as well."	( Interactions of morphine with apomorphine: behavioural and biochemical studies. Kuschinsky, K; Möller, HG, 1986)	0.94
"Pretreatment with morphine did not change the naloxone effects in intact rats."	( Opiate-androgen interactions in drug-induced yawning and penile erections in the rat. Berendsen, HH; Gower, AJ, 1986)	0.59

Toxicity

Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent morphine substitute.

Excerpt	Reference	Relevance
"Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent and extremely safe intravenous morphine-like agent in laboratory animals."	( Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs. Janssen, PA; Niemegeers, CJ; Schellekens, KH; Van Bever, WF, 1976)	0.7
"It has been shown in both mice and rats that the LD50 value for doxapram is reduced in rodents treated with narcotic analgesics."	( A study of the enhanced toxicity of doxapram in rodents treated with narcotic analgesics. Pleuvry, BJ, 1978)	0.26
" Naltrexone (10 mg/kg, ip) given 5 min before pentobarbital did not alter the LD50 of the latter."	( Studies of the possible role of brain endorphins in pentobarbital anesthesia and toxicity in mice. Bhargava, HN, 1979)	0.26
"0 mg kg-1), but not higher doses, significantly antagonized the toxic response to a previously determined TD50 of domoic acid."	( Morphine differentially affects domoic acid and kainic acid toxicity in vivo. Strain, SM; Tasker, A, 1992)	1.73
"The primary purpose of this study was to examine whether alprazolam pretreatment can increase the analgesic potency of morphine without increasing opioid side-effect intensities."	( Influence of alprazolam on opioid analgesia and side effects during steady-state morphine infusions. Coda, BA; Hill, HF; Mackie, A, 1992)	0.72
" Both drugs produced acceptable analgesia, and there were no clinically significant adverse events."	( Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Erdmann, W; Houmes, RJ; Lachmann, B; Verkaaik, A; Voets, MA, 1992)	0.55
" In chronic or acute renal insufficiency biologically active metabolites of morphine accumulate in the serum and may be responsible for severe toxic side effects."	( [Pharmacokinetic effects in morphine toxicity, with case examples]. Morant, R; Senn, HJ, 1991)	0.8
"Single-dose caudal epidural morphine in children is safe and effective when administered intraoperatively prior to surgery as the only opioid and coupled with appropriate monitoring, nursing education, and follow-up by the anesthesiologist."	( Single-dose caudal epidural morphine in children: safe, effective, and easy. Serlin, S, )	0.72
"The analgesic and acute central nervous system (CNS) side effect potential of the enkephalinase inhibitor SCH 32615 (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenyl-alanine-beta-alanine) were evaluated after IV administration to mice, rats and squirrel monkeys."	( Analgesic and acute central nervous system side effects of the intravenously administered enkephalinase inhibitor SCH 32615. Chipkin, RE; Coffin, VL, 1991)	0.28
" Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators."	( Analgesic efficacy and safety of single-dose oral and intramuscular ketorolac tromethamine for postoperative pain. Brown, CR; Bynum, LJ; Clarke, PJ; Dickie, G; Evans, SA; Moodie, JE; Smith, BA; Wild, VM, 1990)	0.28
" We, therefore, devised a technique for tracheal suctioning using inexpensive, readily available materials that is not only safe and effective in suctioning meconium but is also practical and easy to perform."	( A meconium suctioning device that is safe and practical. Alexander, HG; Coraggio, MJ; Roscelli, JD, 1989)	0.28
"A double-blind study of patients selected at random compared the analgesic and adverse effects of intrathecal methadone (1 mg) with those of intrathecal morphine (0."	( Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects. Brody, MC; Chabal, C; Ireton, RC; Jacobson, L; Ward, RJ, 1989)	0.78
" These data establish comparable analgesic efficacy and side effect potential of these two dosage strengths and confirm a 12-hour duration of effect for both."	( Oral controlled-release morphine sulfate. Analgesic efficacy and side effects of a 100-mg tablet in cancer pain patients. Fitzmartin, R; Kaiko, RF; Kanner, R; Maldonado, M; Portenoy, RK, 1989)	0.58
"The ionic composition of the internal environment influences the toxic effect of morphine."	( Experimental research of the influence of the body electrolytic composition on the toxic effect of morphine. Fulga, I; Manu, D; Stroescu, V, )	0.57
" Pain measurements, supplementary analgesia requirements, and adverse effects were recorded."	( A dose-response study of intrathecal morphine: efficacy, duration, optimal dose, and side effects. Brody, MC; Chabal, C; Jacobson, L, 1988)	0.55
" A fixed dose of Ch (100 mg/kg) altered neither the expression of toxic cholinergic signs produced by varying doses (from 75."	( The effects of choline on soman-induced analgesia and toxicity. Romano, JA; Shih, TM, )	0.13
" LD50 of acutely administered iv gentamicin was 51."	( Morphine effects on gentamicin disposition and toxicity in mice. Ben-Zvi, Z; Garty, M; Hurwitz, A, 1988)	1.72
" Adverse effects were very uncommon."	( Use of sodium nitroprusside in neonates: efficacy and safety. Ariagno, RL; Benitz, WE; Cohen, RS; Malachowski, N; Stevenson, DK; Sunshine, P, 1985)	0.27
" lidocaine, as shown by marked reduction of LD50 by either opioid."	( Opioid effects on lidocaine disposition and toxicity in mice. Ben-Zvi, Z; Garty, M; Hurwitz, A, 1985)	0.27
", decreased or less markedly accelerated than might be expected given the reduced blood pressure, suggesting a vagal mechanism for the adverse effects."	( Adverse effects due to morphine sulfate. Challenge to previous clinical doctrine. Jaffe, AS; Semenkovich, CF, 1985)	0.58
"Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double-blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain."	( Adverse effects of commonly ordered oral narcotics. Hopper, M; Kantor, TG; Laska, E, 1981)	0.26
" Toxic signs of oripavine and phi-dihydrothebaine in both species were clonic-tonic convulsions followed by death."	( Analgesic activity and toxicity of oripavine and phi-dihydrothebaine in the mouse and rat. Yeh, SY, 1981)	0.26
" Therefore, continuous intravenous morphine is effective and safe therapy."	( Safety and efficacy of continuous intravenous morphine for severe cancer pain. Citron, ML; Cohen, MH; Fossieck, BE; Franklin, R; Johnston-Early, A; Krasnow, SH; Spagnolo, SV, 1984)	0.8
" Nalorphine (20 mg/kg) did not affect the toxic action of kainic acid."	( Effects of morphine, nalorphine and morphine withdrawal on lethal toxicity of intracerebroventricular kainic acid in mice. Czuczwar, SJ; Kleinrok, Z; Turski, L, 1981)	0.65
" An effort was made to establish safe limits of variable decelerations."	( [Studies on the safe limit of variable decelerations during labor]. Arai, K; Ikegawa, A; Okawa, T; Okinaga, S; Ota, T; Yoshie, K, 1982)	0.26
" With the exception of one subject, who experienced transient (2 hours) nausea, none of the subjects experienced any adverse side effects after the intravenous morphine."	( Nonrespiratory side effects of epidural morphine. Bromage, PR; Camporesi, EM; Durant, PA; Nielsen, CH, 1982)	0.73
"This study showed that the LD50 values for morphine sulfate, cobalt chloride, and phenytoin sodium did not vary significantly on Day 9 of gestation in CF-1 mice when compared to values of nongravid animals."	( Nonvariance of LD50 values of drugs in gravid and nongravid mice. Gautieri, RF; Mahalik, MP; McDevitt, JM; Russell, JA, 1980)	0.52
"The active morphine metabolite, morphine-6-glucuronide (M-6-G), may contribute to both the analgesia and the adverse effects observed during morphine (MOR) therapy."	( Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients. Foley, KM; Inturrisi, CE; Lapin, J; Portenoy, RK; Thaler, HT; Tiseo, PJ, 1995)	2.12
" Our results showed that a large, acute dose of morphine given to drug-naive male rats 24 hr before the initiation of breeding had no effect on fertility rates, but produced several adverse effects on fetal outcome."	( Adverse effects of paternal opiate exposure on offspring development and sensitivity to morphine-induced analgesia. Adams, M; Cicero, TJ; Meyer, ER; Nock, B; O'Connor, L, 1995)	0.77
" The maximum safe (non-lethal) dose of free morphine was 130 mg/kg."	( Prolonged analgesia and decreased toxicity with liposomal morphine in a mouse model. Grant, GJ; Langerman, L; Stenner, M; Turndorf, H; Vermeulen, K; Zakowski, MI, 1994)	0.79
"The efficacy of morphine by either lumbar extradural route or caudal extradural route and their adverse effects for postoperative analgesia were studied by comparing with the control group without morphine administration."	( Lumbar extradural morphine and caudal extradural morphine for postoperative analgesia and their adverse effects. Chan, HC; Chen, FS; Chen, KP; Chuah, EC; Tan, PP; Wong, CH, 1993)	0.97
"The study was designed to compare analgesic efficacy and associated adverse effects between a group of parturients receiving subarachnoid opioids via the combined spinal-epidural (CSE) technique with a group receiving epidural analgesia alone for labor."	( Subarachnoid morphine and fentanyl for labor analgesia. Efficacy and adverse effects. Caldwell, LE; Rosen, MA; Shnider, SM, )	0.5
" These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine."	( Acute interactions of buprenorphine with intravenous cocaine and morphine: an investigational new drug phase I safety evaluation. Kuehnle, J; Mello, NK; Mendelson, JH; Rhoades, EM; Sintavanarong, P; Teoh, SK, 1993)	0.72
"The end points analyzed were adverse effects, duration of postoperative ileus, degree of pain control, length of hospitalization, and development of postoperative confusion as measured on serial MMSEs."	( Does patient-controlled analgesia achieve better control of pain and fewer adverse effects than intramuscular analgesia? A prospective randomized trial. Avecilla, CS; Berg, RL; Nitschke, LF; Schlösser, CT; Selthafner, JV; Wengert, TJ, 1996)	0.29
"Only two patients, both in the PCA group, reported adverse effects; neither required a change in analgesia group."	( Does patient-controlled analgesia achieve better control of pain and fewer adverse effects than intramuscular analgesia? A prospective randomized trial. Avecilla, CS; Berg, RL; Nitschke, LF; Schlösser, CT; Selthafner, JV; Wengert, TJ, 1996)	0.29
" Most patients should probably be managed with PCA narcotics, but the addition of ketorolac might reduce narcotic dose and resultant adverse effects."	( Does patient-controlled analgesia achieve better control of pain and fewer adverse effects than intramuscular analgesia? A prospective randomized trial. Avecilla, CS; Berg, RL; Nitschke, LF; Schlösser, CT; Selthafner, JV; Wengert, TJ, 1996)	0.29
" Adverse effects were rated by a structured interview."	( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996)	0.67
" In PMs, adverse effects were significantly more pronounced on morphine than on codeine and only showed a slight difference between codeine and placebo."	( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996)	0.91
"This study confirms that codeine O-demethylation depends on CYP2D6; it shows that the 6-glucuronidation of morphine is independent of CYP2D6; it supports the theory that the analgesic effect of codeine depends on its O-demethylation; and it indicates that this is probably also the case for the adverse effects."	( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996)	0.89
" The effect of methamphetamine on morphine-dependent mice was investigated by calculating the LD50 (i."	( Increased toxicity of methamphetamine in morphine-dependent mice. al-Shabanah, OA; Bakheet, SA; Ginawi, OT, 1997)	0.84
"Levels of sedation, pain intensity, pain relief, and adverse events were recorded at baseline, at 2, 4, and 6 hours, and at termination."	( Evaluation of the safety and efficacy of ketorolac versus morphine by patient-controlled analgesia for postoperative pain. Bynum, L; Fanciullo, G; Hubbard, L; Maneatis, T; O'Hara, DA; Seuffert, P; Shefrin, A, )	0.38
"The aim of the present study was to assess the toxic potential of drugs of abuse and other neuropharmacological agents in the pathogenesis of AIDS dementia complex (ADC), the neurological complication of AIDS."	( Regulation of glutathione and cell toxicity following exposure to neurotropic substances and human immunodeficiency virus-1 in vitro. Demuth, M; Götz, ME; Koutsilieri, E; Riederer, P; Sauer, U; Sopper, S; ter Meulen, V, 1997)	0.3
"We audited and analysed the adverse effects and safety of postoperative pain management on 2509 consecutive patients under care of the Acute Pain Service at a tertiary referral teaching hospital over a 32-month period."	( An audit of the safety of an acute pain service. Chan, WS; Fung, SK; Hui, TW; Irwin, MG; Ng, KF; O'Reagan, AM; Tsui, SL; Wong, CM, 1997)	0.3
" The incidence of adverse events during the sedation period was also similar."	( Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient. Alted-Lopez, E; Ambros-Checa, A; Caballero-Cubedo, RE; Cantalapiedra-Santiago, JA; Perez-Vela, JL; Sanchez-Izquierdo-Riera, JA, 1998)	0.3
" There were no significant differences in adverse effects (P=."	( Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. Babul, N; Belzile, M; Bruera, E; Darke, A; Fainsinger, R; Ford, I; Harsanyi, Z; Pituskin, E, 1998)	0.5
"Controlled-release oxycodone is as safe and effective as controlled-release morphine in the treatment of cancer pain."	( Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. Babul, N; Belzile, M; Bruera, E; Darke, A; Fainsinger, R; Ford, I; Harsanyi, Z; Pituskin, E, 1998)	0.73
"To assess the effect of opioid substitution (substituting one member of the opioid class for another) on the incidence and severity of adverse effects in palliative care patients who experience unacceptable, refractory adverse effects when taking an opioid drug."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
" 49 substitutions were for adverse effects."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
"We found that the incidence and severity of adverse effects differed between opioids in the same patient."	( Opioid substitution to reduce adverse effects in cancer pain management. Ashby, MA; Jackson, KA; Martin, P, 1999)	0.3
" The OSR group experienced almost twice as many adverse events as did the two MSC groups and also reported somnolence and dizziness more frequently."	( Analgesic efficacy and safety of two oral controlled-release morphine preparations in orthopedic postoperative pain. Buckley, BJ; Cooper, SA; Fitzmartin, R; Goldenheim, PD; Hersh, EV; Kaiko, R; Mooar, P; Slywka, J; Witte, JF, )	0.37
"We report the analgesic and adverse effects of intrathecally administered hyperbaric neostigmine, alone or combined with morphine, in two patients suffering from severe lower limb ischaemic pain (group 1), five patients undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic surgery (group 3) under spinal anaesthesia."	( Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or combined with morphine in patients submitted to spinal anaesthesia: pilot studies. Garcia, LV; Klamt, JG; Prado, WA, 1999)	0.72
"Nausea and vomiting are frequent adverse effects of patient-controlled analgesia (PCA) with opioids."	( Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: a quantitative systematic review. Tramèr, MR; Walder, B, 1999)	0.3
" There is no evidence of dose-responsiveness for efficacy with droperidol, but the risk of adverse effects is dose-dependent."	( Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: a quantitative systematic review. Tramèr, MR; Walder, B, 1999)	0.3
" Slow DM metabolizers took significantly lower daily doses of MorphiDex than rapid metabolizers without a significant difference in the incidence of adverse events."	( Long-term safety of MorphiDex. Goldblum, R, 2000)	0.31
"PCA is safe and effective for morbidly obese patients following RYGBP."	( Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery. Brolin, RE; Choi, YK; Chou, S; Etesham, S; Pollak, P; Wagner, BK, 2000)	0.31
" Constipation scores increased while other side effect scores were unaltered."	( Pain intensity and side effects during titration of morphine to cancer patients using a fixed schedule dose escalation. Borchgrevink, PC; Kaasa, S; Klepstad, P; Skauge, M, 2000)	0.56
"Because of the well known adverse effects that may be associated with pethidine use, the authors recommend that morphine should be the preferred agent in suspected renal colic, when an opioid analgesic is to be used."	( A comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. Cardwell, H; O'Connor, A; Schug, SA, 2000)	0.78
"The newly developed controlled-release M suppository is safe and effective and may be a useful alternative for oral morphine administration in patients with cancer pain."	( Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain. Frijlink, HW; Meijler, WJ; Moolenaar, F; Proost, JH; Visser, J, 2000)	0.74
"We performed a prospective, randomized, double-blinded, multicenter study to compare the analgesic efficacy and adverse effects of intrathecal nalbuphine, at three different doses, and intrathecal morphine for postoperative pain relief after cesarean deliveries."	( Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects. Culebras, X; Gaggero, G; Kern, C; Marti, RA; Zatloukal, J, 2000)	0.73
"Small doses of intrathecal nalbuphine produce fewer adverse effects, such as pruritus and postoperative nausea and vomiting, compared with intrathecal morphine."	( Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects. Culebras, X; Gaggero, G; Kern, C; Marti, RA; Zatloukal, J, 2000)	0.74
"To investigate the effect of acute P-glycoprotein inhibition by the multidrug-resistance (MDR) modulator valspodar (SDZ PSC 833; PSC) on the pharmacokinetics, and potentially adverse pharmacodynamic effects of morphine, and its principal pharmacologically active metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.71
"In a double-blind, three-way crossover study, the pharmacokinetic and potentially adverse pharmacodynamic effects (reaction time, transcutaneous PCO2, blood pressure) of morphine were compared with and without acute inhibition of P-glycoprotein by PSC."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.72
" PSC did not significantly affect the adverse events of morphine, as assessed by spontaneous reporting."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.77
" No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use."	( An assessment of the safety, efficacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study. Zeppetella, G, 2000)	0.31
" Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat."	( Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. Chen, Y; Gurwell, JA; Hauser, KF; Martin, KM; Nath, A; Sun, Q; Zhang, J, 2001)	0.67
"Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects."	( Strategies to manage the adverse effects of oral morphine: an evidence-based report. Cherny, N; Davis, C; Fallon, M; McQuay, H; Mercadante, S; Pasternak, G; Pereira, J; Ripamonti, C; Ventafridda, V, 2001)	0.57
" Adverse effects were comparable in the three groups, except for significantly more nausea in the control group (39% vs."	( Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Fletcher, D; Gillon, MC; Incagnoli, P; Josse, C; Kuhlman, L; Mimoz, O; Mirand, A; Soilleux, H, 2001)	0.31
" In this study, chronic supplementation of intrathecal opioids with bupivacaine was a safe method for providing continued management of chronic pain of cancer or noncancer origin."	( Stability, compatibility, and safety of intrathecal bupivacaine administered chronically via an implantable delivery system. Deer, TR; Elsberry, DD; Hildebrand, KR, 2001)	0.31
"In this study, we have focused our investigation of the facts whether co-administration of a NMDA antagonist dextromethorphan (DM) with morphine during pregnancy and throughout lactation could prevent the adverse effects associated with chronic morphine administration in rat offspring."	( Co-administration of dextromethorphan during pregnancy and throughout lactation significantly decreases the adverse effects associated with chronic morphine administration in rat offspring. Su, CH; Tao, PL; Wu, YH; Yeh, GC, 2001)	0.71
"Postoperative epidural infusion of levobupivacaine can provide safe and effective analgesia for patients having hip or knee joint replacement."	( The efficacy and safety of three concentrations of levobupivacaine administered as a continuous epidural infusion in patients undergoing orthopedic surgery. Berman, JS; Dickson, UK; Gad-Elrab, RR; Murdoch, JA; Scott, NB; Wilson, PA, 2002)	0.31
" The most common adverse events were constipation and nausea."	( Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. Babul, N; Caldwell, JR; Davis, JC; Eliot, L; Lynch, PM; Marker, HW; Offenberg, HL; Rapoport, RJ; Roth, SH; Yuan, W, 2002)	0.59
" Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (d-amphetamine and cocaine)."	( Toxic effects of opioid and stimulant drugs on undifferentiated PC12 cells. Macedo, TR; Morgadinho, MT; Oliveira, CR; Oliveira, MT; Rego, AC, 2002)	0.57
"A multi-level ilioinguinal-iliohypogastric nerve block technique can reduce the amount of systemic morphine required to control post-Cesarean delivery pain but this reduction was not associated with a reduction of opioid related adverse effects in our study group."	( Iliohypogastric-ilioinguinal peripheral nerve block for post-Cesarean delivery analgesia decreases morphine use but not opioid-related side effects. Bell, EA; Dexter, F; Greengrass, RA; Jones, BP; Olufolabi, AJ; Penning, DH; Phillips-Bute, B; Reynolds, JD, )	0.56
"The objectives of this study were: (i) to measure the analgesic efficacy and frequency of adverse events following autonomous nurse-initiated intravenous morphine in patients presenting with acute pain, awaiting medical assessment; and (ii) to determine whether such a process would improve the time to analgesia."	( Nurse-initiated intravenous morphine in the emergency department: efficacy, rate of adverse events and impact on time to analgesia. Fry, M; Holdgate, A, 2002)	0.81
"0 cm visual analogue scale and predetermined adverse events defined by physiological parameters were measured at regular intervals over the following 60 min."	( Nurse-initiated intravenous morphine in the emergency department: efficacy, rate of adverse events and impact on time to analgesia. Fry, M; Holdgate, A, 2002)	0.61
" There were 15 predefined adverse events, 10 episodes of hypotension and five episodes of oxygen desaturation."	( Nurse-initiated intravenous morphine in the emergency department: efficacy, rate of adverse events and impact on time to analgesia. Fry, M; Holdgate, A, 2002)	0.61
" It decreases morphine requirements but its effect on the incidence of morphine-related adverse effects remains unknown."	( Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects. Aubrun, F; Bellanger, A; Coriat, P; Kalfon, F; Langeron, O; Mottet, P; Riou, B, 2003)	0.92
" The primary end-point was the incidence of morphine-related adverse effects."	( Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects. Aubrun, F; Bellanger, A; Coriat, P; Kalfon, F; Langeron, O; Mottet, P; Riou, B, 2003)	0.82
"001) but the incidence of morphine-related adverse effects did not differ between groups (42 vs 46%, not significant)."	( Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects. Aubrun, F; Bellanger, A; Coriat, P; Kalfon, F; Langeron, O; Mottet, P; Riou, B, 2003)	0.86
"Although propacetamol induced a small morphine-sparing effect, it did not change the incidence of morphine-related adverse effects in the postoperative period."	( Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects. Aubrun, F; Bellanger, A; Coriat, P; Kalfon, F; Langeron, O; Mottet, P; Riou, B, 2003)	0.83
" The aim was to investigate efficacy, adverse effects and safety of the treatments in a large patient population."	( Pain relief and safety after major surgery. A prospective study of epidural and intravenous analgesia in 2696 patients. Flisberg, P; Linnér, R; Lundberg, CJ; Rudin, A, 2003)	0.32
"In a large patient population the use of epidural and intravenous postoperative analgesia was considered safe in surgical wards, and the incidence of adverse effects was low."	( Pain relief and safety after major surgery. A prospective study of epidural and intravenous analgesia in 2696 patients. Flisberg, P; Linnér, R; Lundberg, CJ; Rudin, A, 2003)	0.32
" Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period."	( Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. Alston, RP; Duke, PC; Feneck, RO; Hsu, PH; Hubbard, RC; Mangano, DT; Nussmeier, NA; Ott, E; Saidman, LJ; Snabes, MC, 2003)	0.32
" Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19."	( Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. Alston, RP; Duke, PC; Feneck, RO; Hsu, PH; Hubbard, RC; Mangano, DT; Nussmeier, NA; Ott, E; Saidman, LJ; Snabes, MC, 2003)	0.32
" However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular."	( Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. Alston, RP; Duke, PC; Feneck, RO; Hsu, PH; Hubbard, RC; Mangano, DT; Nussmeier, NA; Ott, E; Saidman, LJ; Snabes, MC, 2003)	0.32
" The safety was evaluated by monitoring the patient's clinical conditions and adverse events."	( Evaluation of safety and efficacy of transdermal therapeutic system-fentanyl in adult patients with gynecological cancer-related pain. Cheewakriangkrai, C; Katanyoo, K; Lorvidhaya, V; Srisomboon, J; Suprapaphorn, P, 2004)	0.32
" The most frequent adverse events were mild nausea or vomiting (46%) and constipation (33%)."	( Evaluation of safety and efficacy of transdermal therapeutic system-fentanyl in adult patients with gynecological cancer-related pain. Cheewakriangkrai, C; Katanyoo, K; Lorvidhaya, V; Srisomboon, J; Suprapaphorn, P, 2004)	0.32
"The results suggest that TTS-fentanyl is safe and effective in managing chronic gynecological cancer-related pain."	( Evaluation of safety and efficacy of transdermal therapeutic system-fentanyl in adult patients with gynecological cancer-related pain. Cheewakriangkrai, C; Katanyoo, K; Lorvidhaya, V; Srisomboon, J; Suprapaphorn, P, 2004)	0.32
" The incidence of adverse events was low in both groups."	( Intrathecal morphine provides effective and safe analgesia in children after cardiac surgery. But, WW; Eyres, RL; Frawley, G; McKinley, DF; Ragg, PG; Suominen, PK, 2004)	0.7
" Four subjects experienced significant but reversible decreases in FEV1 of > or = 20% compared to baseline and across all dose levels including after placebo, but with no associated increase in dyspnea, wheezing or other adverse events."	( Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma. Linn, L; Morishige, R; Okikawa, J; Otulana, B; Thipphawong, J, 2004)	0.59
" The safety analysis evaluated the incidence of adverse events (AEs) reported within the first 28 days of treatment with TDF or SRM."	( Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain. Ahmedzai, SH; Allan, LG; Camacho, F; Clark, AJ; Horbay, GL; Richarz, U; Simpson, K, 2004)	0.56
" Pediatric day stay tonsillectomy is a safe procedure when performed with strict preoperative criteria, trained day stay unit (DSU) staff, and with in-patient facilities on site."	( Day stay pediatric tonsillectomy--a safe procedure. Anderson, BJ; Barber, C; Brown, C; Douglas, G; Mahadevan, M; Mills, N; Salkeld, L; White, J, 2004)	0.32
" We tested the hypothesis that, in patients having unilateral TKA under intrathecal (IT) anesthesia, the addition of a femoral nerve block would provide superior analgesia when compared with IT morphine and demonstrate fewer adverse side effects."	( A single injection ultrasound-assisted femoral nerve block provides side effect-sparing analgesia when compared with intrathecal morphine in patients undergoing total knee arthroplasty. Beach, M; Gallagher, JD; Jarrett, RA; Lundberg, CJF; Sites, BD; Sparks, MB, 2004)	0.72
"Inadequate analgesia and/or unmanageable adverse events frequently result in the need to rotate patients with cancer pain to a different opioid."	( Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: a pilot study. Ahdieh, H; Slatkin, N; Sloan, P, 2005)	0.33
" Pain was assessed using a visual analog scale, and adverse events were recorded."	( Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: a pilot study. Ahdieh, H; Slatkin, N; Sloan, P, 2005)	0.33
" --It is argued, in this paper, that codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy."	( A review of the efficacy and safety of opioid analgesics post-craniotomy. Roberts, G, )	0.13
"1 mg has been shown to be optimal for effective and safe pain relief after abdominal surgery."	( [Efficacy and safety of 0.1 mg of intrathecal morphine in arthroscopic knee joint surgery]. Decker, T; Eichler, F; Grond, S; Kasper, SM; Müller, E; Rütt, J, 2004)	0.58
" There was no difference between treatments for evaluations of overall pain intensity, analgesic efficacy, or adverse events."	( Efficacy, safety, and steady-state pharmacokinetics of once-a-day controlled-release morphine (MS Contin XL) in cancer pain. Darke, A; Eisenhoffer, J; Hagen, NA; Harsanyi, Z; Quigley, P; Thirlwell, M, 2005)	0.55
" However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men."	( Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia. Campbell, CM; Fillingim, RB; Glover, TL; Hastie, BA; Ness, TJ; Price, DD; Staud, R, 2005)	2.17
"The purpose of this retrospective study was to determine whether epidural fentanyl-bupivacaine patient-controlled analgesia (PCA) was more efficacious and had fewer adverse effects than epidural or intravenous morphine PCA."	( Efficacy and adverse effects of patient-controlled epidural or intravenous analgesia after major surgery. Hu, JS; Liew, C; Lui, PW; Teng, YH; Tsai, SK, 2004)	0.51
" Adverse effects including nausea, vomiting, pruritus, urinary retention, sedation, motor block, and respiratory depression (< 8 breaths per minute) were recorded."	( Efficacy and adverse effects of patient-controlled epidural or intravenous analgesia after major surgery. Hu, JS; Liew, C; Lui, PW; Teng, YH; Tsai, SK, 2004)	0.32
" There were no differences in other adverse events such as urinary retention, sedation, and motor block among the three groups."	( Efficacy and adverse effects of patient-controlled epidural or intravenous analgesia after major surgery. Hu, JS; Liew, C; Lui, PW; Teng, YH; Tsai, SK, 2004)	0.32
" It is considered safe to use continuous epidural PCA with fentanyl-bupivacaine in patients receiving major elective surgery."	( Efficacy and adverse effects of patient-controlled epidural or intravenous analgesia after major surgery. Hu, JS; Liew, C; Lui, PW; Teng, YH; Tsai, SK, 2004)	0.32
" Safety was monitored through adverse event reporting, clinical examination, and laboratory testing."	( Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Groudine, SB; Jahr, JS; Payen-Champenois, C; Reynolds, LW; Sinatra, RS; Viscusi, ER, 2005)	0.33
" Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage."	( Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. Atici, S; Cinel, I; Cinel, L; Doruk, N; Eskandari, G; Oral, U, 2005)	0.33
" However, most of the studies have not demonstrated a decrease in morphine adverse effects."	( Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Bonnet, F; Kurdi, O; Marret, E; Zufferey, P, 2005)	0.79
" Their use is frequently associated with dose-limiting adverse effects."	( Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. Berzsenyi, P; Farkas, S; Kárpáti, E; Kocsis, P; Tarnawa, I, )	0.13
" For detecting side effect liability (ataxia, sedation, impairment of voluntary motor functions), (1) the rota-rod test, (2) measurement of spontaneous motility, (3) the weight-lifting test and (4) the thiopental sleep test were used."	( Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. Berzsenyi, P; Farkas, S; Kárpáti, E; Kocsis, P; Tarnawa, I, )	0.13
"Therapeutic indices calculated from the results of these in vivo experiments for the clinically used muscle relaxants are in agreement with their adverse effect profiles in humans."	( Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. Berzsenyi, P; Farkas, S; Kárpáti, E; Kocsis, P; Tarnawa, I, )	0.13
" The frequency of predefined adjudicated postrandomization adverse events, including cardiovascular thromboembolism, renal dysfunction, gastroduodenal ulceration, and wound-healing complications, was assessed in each group."	( Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery. Boye, ME; Brown, MT; Joshi, GP; Langford, RM; Nussmeier, NA; Singla, NK; Verburg, KM; Whelton, AA, 2006)	0.33
"Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib (2."	( Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery. Boye, ME; Brown, MT; Joshi, GP; Langford, RM; Nussmeier, NA; Singla, NK; Verburg, KM; Whelton, AA, 2006)	0.33
" No deaths, serious adverse events, or withdrawals due to adverse events occurred."	( Safety and efficacy of oral slow release morphine for maintenance treatment in heroin addicts: a 6-month open noncomparative study. Alexieva, DZ; Pavlova, RZ; Vasilev, GN, 2006)	0.6
" Our hypothesis is that there is no difference in the number of adverse events in ketamine sedations with and without morphine pretreatment."	( Adverse events in pediatric ketamine sedations with or without morphine pretreatment. Cohen, DM; Leder, MS; Waterman, GD, 2006)	0.78
" The number and types of adverse events between patients with and without morphine pretreatment were examined."	( Adverse events in pediatric ketamine sedations with or without morphine pretreatment. Cohen, DM; Leder, MS; Waterman, GD, 2006)	0.8
" Twenty-one adverse events were recorded in the group of patients without morphine pretreatment."	( Adverse events in pediatric ketamine sedations with or without morphine pretreatment. Cohen, DM; Leder, MS; Waterman, GD, 2006)	0.8
"We found no increase in the number of adverse events with morphine pretreatment in ketamine sedations for children."	( Adverse events in pediatric ketamine sedations with or without morphine pretreatment. Cohen, DM; Leder, MS; Waterman, GD, 2006)	0.82
" Adverse effects, pain reduction at 5 minutes and 2 hours postbaseline, and additional analgesics and antiemetics were tracked as secondary outcome measures."	( Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial. Bijur, PE; Chang, AK; Gallagher, EJ; Kenny, MK; Meyer, RH; Solorzano, C, 2006)	0.57
" Adverse effects were similar in both groups, with the exception of pruritus, which did not occur in patients receiving hydromorphone (0% versus 6% [difference -6%; 95% confidence interval -11% to -1%])."	( Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial. Bijur, PE; Chang, AK; Gallagher, EJ; Kenny, MK; Meyer, RH; Solorzano, C, 2006)	0.57
" The intravenous route has been proven to be safe and effective, providing rapid analgesia in patients receiving oral morphine."	( Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. Aielli, F; Casuccio, A; Ferrera, P; Mercadante, S; Porzio, G; Verna, L; Villari, P, 2006)	0.81
" Abdominal adverse effects of opioid analgesics are constipation and increased pressure in the biliary system."	( Prospective sonographic evaluation of fentanyl side effects on the neonatal gallbladder. Benz-Bohm, G; Roth, B; Schmidt, B; Stützer, H, 2006)	0.33
" Further investigations are required to assess adverse gastrointestinal effects."	( Prospective sonographic evaluation of fentanyl side effects on the neonatal gallbladder. Benz-Bohm, G; Roth, B; Schmidt, B; Stützer, H, 2006)	0.33
" Total daily morphine dose had little impact on side-effect patterns."	( The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain. Glare, P; Sheehan, D; Walsh, D, )	0.81
" During the 4-week study period, the analgesic efficacy and adverse effects related to intrathecal betamethasone were observed."	( Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety. Oishi, K; Sakamoto, S; Shingu, K; Taguchi, H, 2007)	0.34
" Adverse effects related to neurotoxicity of intrathecal betamethasone, such as sensory and motor dysfunctions, were not observed in any patients."	( Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety. Oishi, K; Sakamoto, S; Shingu, K; Taguchi, H, 2007)	0.34
"When conventional cancer pain treatments are not successful, intrathecal betamethasone may be useful, as it probably induces long-lasting analgesia without adverse effects and improves activities of daily living, especially in patients with vertebral bone metastases."	( Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety. Oishi, K; Sakamoto, S; Shingu, K; Taguchi, H, 2007)	0.34
" In this limited sample, extending the infusion period from the presently approved 48 hours to 96 hours seems to be a safe alternative and/or adjunct to standard opiate analgesia after colorectal surgery using a right lateral transverse incision, hence reducing the incidence of opiate adverse effects and enhancing recovery."	( Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection. Corso, OH; Hewett, PJ; Karatassas, A; Morris, RG, 2007)	0.34
" Some patients may benefit from a 20-mg dose, but the incidence of serious adverse respiratory events has been close related in clinical trials."	( Extended-release lipid-foam encapsulated epidural morphine: clinical efficacy and safety precautions. Hutchison, R, )	0.38
" Safety assessment showed no adverse effects on renal or hepatic function tests, surgical drain output, or continuous oximetry between placebo and ketorolac groups."	( Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anderson, GD; Bradford, H; Chen, J; Ellenbogen, RG; Kantor, ED; Lynn, AM; Salinger, DH; Seng, KY; Vicini, P, 2007)	0.56
" No adverse effects on surgical drain output, oximetry measured saturations, renal or hepatic function tests were seen."	( Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anderson, GD; Bradford, H; Chen, J; Ellenbogen, RG; Kantor, ED; Lynn, AM; Salinger, DH; Seng, KY; Vicini, P, 2007)	0.56
" The adverse effects noticed were thirst feeling, itching, nausea, vomiting and urinary retention."	( [Sexual differences in effects and side effects of epidural morphine for VATS (video-associated thoracic surgery)]. Kawagoe, I; Sumida, T, 2007)	0.58
" Adverse events were recorded and categorized by system effect."	( The analgesic efficacy and safety of intra-articular morphine and mepivicaine following temporomandibular joint arthroplasty. Ibanez, C; Kozacko, M; Zuniga, JR, 2007)	0.59
" No serious adverse events occurred in this study."	( The analgesic efficacy and safety of intra-articular morphine and mepivicaine following temporomandibular joint arthroplasty. Ibanez, C; Kozacko, M; Zuniga, JR, 2007)	0.59
" In this situation, newborns might be exposed to toxic levels of morphine when breastfeeding."	( Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. Aleksa, K; Cairns, J; Chitayat, D; Gaedigk, A; Karaskov, T; Koren, G; Leeder, JS; Madadi, P; Teitelbaum, R, 2007)	0.84
" Primary resection and anastomosis is a safe option in the treatment of complicated meconium ileus."	( Primary resection and anastomosis for complicated meconium ileus: a safe procedure? Bianchi, A; Bowen, J; Bruce, J; Jawaheer, J; Khalil, B; Morabito, A; Morecroft, J; Plummer, T; Rakoczy, G, 2007)	0.34
" Pain intensity, relative dosing ratios, discontinuation rates, and adverse events were assessed."	( The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies. Damaraju, CV; Hewitt, DJ; Kershaw, P; Siccardi, M; Viscusi, ER, 2007)	0.56
" Discontinuation rates and the incidence of adverse events were similar between groups."	( The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies. Damaraju, CV; Hewitt, DJ; Kershaw, P; Siccardi, M; Viscusi, ER, 2007)	0.56
" Application of morphine before each dose of DOX either significantly reduced or completely prevented its toxic effects."	( Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Dehpour, AR; Ejtemaeemehr, S; Kelishomi, RB; Mobarakeh, JI; Rahimian, R; Tavangar, SM, 2008)	2.13
" Commonly occurring adverse events were similar between groups."	( Efficacy and safety of the fentanyl iontophoretic transdermal system (ITS) and intravenous patient-controlled analgesia (IV PCA) with morphine for pain management following abdominal or pelvic surgery. Damaraju, CV; Gargiulo, K; Hewitt, DJ; Minkowitz, HS; Rathmell, JP; Vallow, S, )	0.33
" Hemodynamic data, sedation scores, and renal and hepatic function were assessed for control of adverse events."	( Clinical analgesic efficacy and side effects of dexmedetomidine in the early postoperative period after arthroscopic knee surgery. Gómez-Vázquez, ME; Hernández-Jiménez, A; Hernández-Salazar, E; Pérez-Sánchez, A; Salazar-Páramo, M; Zepeda-López, VA, 2007)	0.34
" The most frequent adverse events with dexmedetomidine were bradycardia and hypertension."	( Clinical analgesic efficacy and side effects of dexmedetomidine in the early postoperative period after arthroscopic knee surgery. Gómez-Vázquez, ME; Hernández-Jiménez, A; Hernández-Salazar, E; Pérez-Sánchez, A; Salazar-Páramo, M; Zepeda-López, VA, 2007)	0.34
"Using lower bolus doses, pain relief in the immediate postoperative period with morphine was as efficacious and safe in elderly patients as in younger patients."	( Age-adapted morphine titration produces equivalent analgesia and adverse effects in younger and older patients. Desmonts, JM; Keïta, H; Maalouli, J; Mantz, J; Tubach, F, 2008)	0.95
" Safety assessments included adverse events and nasal examination."	( Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Carr, DB; Ernst, C; Gawarecki, D; Hamilton, D; McNicol, E; Mermelstein, F; Reber, KR; Stoker, DG; Waltzman, LS; Wright, C, )	0.41
" Local adverse events associated with IN morphine were transient and mostly mild (bad taste, nasal congestion, throat irritation, and sneezing)."	( Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Carr, DB; Ernst, C; Gawarecki, D; Hamilton, D; McNicol, E; Mermelstein, F; Reber, KR; Stoker, DG; Waltzman, LS; Wright, C, )	0.68
"By multiple measures of pain intensity and pain relief, IN morphine provides sustained analgesia in postsurgical patients and thus may offer a safe and less invasive alternative to IV morphine."	( Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Carr, DB; Ernst, C; Gawarecki, D; Hamilton, D; McNicol, E; Mermelstein, F; Reber, KR; Stoker, DG; Waltzman, LS; Wright, C, )	0.66
" Clinical data, including pain and side-effect scores, were correlated with genotype data."	( Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. du Bois, RM; Gretton, S; Riley, J; Ross, JR; Sato, H; Taegetmeyer, AB; Welsh, KI, 2008)	0.63
" Change in self-reported pain intensity from baseline to 30 minutes postbaseline on a validated and reproducible 11-point numerical rating scale and count of adverse events were the primary outcomes."	( Response to morphine in male and female patients: analgesia and adverse events. Bijur, PE; Birnbaum, A; Chang, AK; Esses, D; Gallagher, EJ; Schechter, C, )	0.51
" In women without nausea before administration of morphine, the incidence of adverse events was 18."	( Response to morphine in male and female patients: analgesia and adverse events. Bijur, PE; Birnbaum, A; Chang, AK; Esses, D; Gallagher, EJ; Schechter, C, )	0.76
" Women without baseline nausea had more adverse events than men."	( Response to morphine in male and female patients: analgesia and adverse events. Bijur, PE; Birnbaum, A; Chang, AK; Esses, D; Gallagher, EJ; Schechter, C, )	0.51
"To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine."	( Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. Maltoni, M; Raffaeli, W; Sartori, S; Scarpi, E; Tamburini, E; Tassinari, D; Tombesi, P, 2008)	0.77
" The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal."	( Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. Maltoni, M; Raffaeli, W; Sartori, S; Scarpi, E; Tamburini, E; Tassinari, D; Tombesi, P, 2008)	0.56
" No significant differences were observed for overall adverse effects, overall gastrointestinal adverse effects, overall neurologic adverse effects, nausea, somnolence, hypoventilation, trial withdrawal, and changes in opiate treatments."	( Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. Maltoni, M; Raffaeli, W; Sartori, S; Scarpi, E; Tamburini, E; Tassinari, D; Tombesi, P, 2008)	0.56
"Although no difference in the overall adverse effect profile exists between transdermal opiates and slow release oral morphine, the difference in some adverse effects (mainly constipation) seems to favor transdermal opiates in the preference of patients with moderate-severe cancer pain."	( Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. Maltoni, M; Raffaeli, W; Sartori, S; Scarpi, E; Tamburini, E; Tassinari, D; Tombesi, P, 2008)	0.77
" The occurrence of adverse events and changes in laboratory tests were evaluated as safety variables."	( Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain. Hanaoka, K; Hosokawa, T; Ishida, T; Kitajima, T; Mashimo, S; Miyazaki, T; Namiki, A; Nogami, S; Ogawa, S, 2008)	0.35
" A total of 316 adverse events occurred in 78 (90."	( Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain. Hanaoka, K; Hosokawa, T; Ishida, T; Kitajima, T; Mashimo, S; Miyazaki, T; Namiki, A; Nogami, S; Ogawa, S, 2008)	0.35
" The patch tested was well tolerated and its use did not result in any increased incidence of adverse drug reactions over those commonly found with opioid analgesics."	( Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain. Hanaoka, K; Hosokawa, T; Ishida, T; Kitajima, T; Mashimo, S; Miyazaki, T; Namiki, A; Nogami, S; Ogawa, S, 2008)	0.35
" The search for opioid analgesics with a better side-effect profile than morphine has led to a morphine metabolites, morphine-6-glucuronide (M6G)."	( Morphine-6-glucuronide: potency and safety compared with morphine. Dahan, A; Morariu, A; van Dorp, EL, 2008)	2.02
"The objectives of the current paper are to give an overview of the analgesic properties of M6G, assess the dose range at which it produces equianalgesia to morphine and explore its side-effect profile."	( Morphine-6-glucuronide: potency and safety compared with morphine. Dahan, A; Morariu, A; van Dorp, EL, 2008)	1.99
" However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown."	( Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain. Lin, CJ; Lin, FS; Lin, TF; Sun, WZ; Wang, YP; Yeh, YC, 2008)	0.9
" Patient-controlled analgesia (PCA) requirement, postoperative pain, and adverse events were evaluated throughout the postoperative 24 h period."	( Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain. Lin, CJ; Lin, FS; Lin, TF; Sun, WZ; Wang, YP; Yeh, YC, 2008)	0.55
" In contrast, mu-opioids are highly active as analgesics against a range of nociceptive stimuli, but also concomitantly elicit strongly adverse effects."	( Antinociceptive and adverse effects of mu- and kappa-opioid receptor agonists: a comparison of morphine and U50488-H. Gallantine, EL; Meert, TF, 2008)	0.56
"Despite "clinical lore" among health care providers that treatment with hydromorphone results in improved pain control and fewer adverse side effects, morphine continues to be the first-line medication for postoperative patient-controlled analgesia (PCA)."	( The side effects of morphine and hydromorphone patient-controlled analgesia. Diaz, G; Flood, P; Hong, D, 2008)	0.87
"The side effect profile was not different between drugs."	( The side effects of morphine and hydromorphone patient-controlled analgesia. Diaz, G; Flood, P; Hong, D, 2008)	0.67
" Patients were assessed for pain control and adverse events."	( Morphine infusions after pediatric cranial surgery: a retrospective analysis of safety and efficacy. Bowen-Roberts, T; Hammond, AM; Kent, SK; Ou, CH; Steinbok, P; Warren, DT, 2008)	1.79
"These findings suggest that CMI is as safe a treatment option as acetaminophen and codeine."	( Morphine infusions after pediatric cranial surgery: a retrospective analysis of safety and efficacy. Bowen-Roberts, T; Hammond, AM; Kent, SK; Ou, CH; Steinbok, P; Warren, DT, 2008)	1.79
"Dopamine receptor antagonists are commonly used to counter the adverse effects of opioids such as hallucinations, delusions and emesis."	( Suppression of dopamine-related side effects of morphine by aripiprazole, a dopamine system stabilizer. Amano, T; Asato, M; Hashimoto, K; Ikegami, D; Kuzumaki, N; Matsushima, Y; Nakamura, A; Narita, M; Niikura, K; Shiokawa, M; Suzuki, T; Takagi, S; Takei, D; Tsurukawa, Y, 2008)	0.6
" A meta-analysis approach was used to assess the adverse effects of EREM (n = 801) in comparison with intravenous opioids and standard epidural morphine."	( Extended-release epidural morphine (DepoDur): review and safety analysis. Hartrick, CT; Hartrick, KA, 2008)	0.85
" Safety assessments included adverse event recording and nasal examinations."	( The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model. Babul, N; Carr, DB; Christensen, KS; Cohen, AE; Hamilton, DA; McNicol, E; Mermelstein, FH, 2008)	0.59
" Study medications were generally well tolerated, with no withdrawals due to adverse events or other safety concerns, and no serious adverse events reported."	( The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model. Babul, N; Carr, DB; Christensen, KS; Cohen, AE; Hamilton, DA; McNicol, E; Mermelstein, FH, 2008)	0.59
" This procedure is safe and effective and we recommend this as the first treatment for MO in ELBW infants."	( Iopamidol enema treatment for meconium obstruction of prematurity in extremely low-birth weight infants: a safe and effective method. Funato, M; Nakaoka, T; Nishihara, M; Shiokawa, C; Tamai, H; Uemura, S, 2009)	0.35
"This procedure is safe and effective."	( Iopamidol enema treatment for meconium obstruction of prematurity in extremely low-birth weight infants: a safe and effective method. Funato, M; Nakaoka, T; Nishihara, M; Shiokawa, C; Tamai, H; Uemura, S, 2009)	0.35
"" Adverse effects, pain reduction at 10 minutes and 2 hours postbaseline, patient evaluations of satisfaction and pain relief at 30 minutes postbaseline, and use of additional analgesics and antiemetics were tracked as secondary outcomes."	( Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: a prospective, randomized, double-blind clinical trial. Baccelieri, A; Bijur, PE; Chang, AK; Gallagher, EJ, 2009)	0.58
" The incidence of adverse effects from baseline to 30 minutes was not statistically different in the 2 groups."	( Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: a prospective, randomized, double-blind clinical trial. Baccelieri, A; Bijur, PE; Chang, AK; Gallagher, EJ, 2009)	0.58
" The incidence of adverse effects was not statistically different."	( Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: a prospective, randomized, double-blind clinical trial. Baccelieri, A; Bijur, PE; Chang, AK; Gallagher, EJ, 2009)	0.58
" Study variables included pain intensity on a visual analog scale every 4 hours, need for rescue analgesia (morphine), complications and adverse events within 5 postoperative days."	( [Epidural analgesia versus femoral or femoral-sciatic nerve block after total knee replacement: comparison of efficacy and safety]. Bartrons Vilarnau, R; Bisbe Vives, E; Castillo Monsegur, J; Escolano Villén, F; Ginés Cespedosa, A; Montes Pérez, A; Santiveri Papiol, X, 2009)	0.57
" Peripheral nerve block techniques have fewer adverse side effects than epidural analgesia."	( [Epidural analgesia versus femoral or femoral-sciatic nerve block after total knee replacement: comparison of efficacy and safety]. Bartrons Vilarnau, R; Bisbe Vives, E; Castillo Monsegur, J; Escolano Villén, F; Ginés Cespedosa, A; Montes Pérez, A; Santiveri Papiol, X, 2009)	0.35
" The results of our study suggest that preoperative ITM combined with IV-PCA may be considered as an effective and safe pain management regimen in living liver donors who have characteristics of low tolerance to pain and postoperative coagulation derangement."	( Intrathecal morphine combined with intravenous patient-controlled analgesia is an effective and safe method for immediate postoperative pain control in live liver donors. Ahn, HJ; Cho, HS; Choi, SJ; Gwak, MS; Hahm, TS; Joh, JW; Kim, GS; Kim, JA; Kim, KM; Ko, JS, 2009)	0.73
" CONCLUSION / CLINICAL RELEVANCE: Dexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted."	( Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs. Aspegrén, J; Hellebrekers, LJ; McKusick, BC; Murrell, JC; Robben, JH; Uilenreef, J; Valtolina, C, 2009)	0.35
" However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord."	( Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects. , 2008)	0.35
" Numerical rating score, PCA requirement, nausea, vomiting, use of antiemetics, pruritus, use of antipruritics, and opioid-related adverse events were investigated at 1, 2, 4, and 24 hours postoperatively."	( Combination of low-dose nalbuphine and morphine in patient-controlled analgesia decreases incidence of opioid-related side effects. Chan, WS; Chang, HC; Lin, CJ; Lin, TF; Sun, WZ; Wang, YP; Yeh, YC, 2009)	0.62
"This study was conducted to identify patient-related, surgical, and anesthetic factors that would help predict adverse events and allow for better planning of perioperative care in children with myotonic dystrophy."	( Risk factors for perioperative adverse events in children with myotonic dystrophy. Reed, PW; Sinclair, JL, 2009)	0.35
" Perioperative adverse events were recorded."	( Risk factors for perioperative adverse events in children with myotonic dystrophy. Reed, PW; Sinclair, JL, 2009)	0.35
" This study examined the structure and predictive validity of somatic and cognitive/affective side-effect profiles of morphine and pentazocine using the Somatic Side Effects Questionnaire and the Cognitive and Affective Side Effects Questionnaire."	( Cognitive-affective and somatic side effects of morphine and pentazocine: side-effect profiles in healthy adults. Campbell, CM; Fillingim, RB; Glover, TL; Hastie, BA; Riley, JL; Staud, R, 2010)	0.83
" These drug-related side-effect profiles were linked with analgesic responses."	( Cognitive-affective and somatic side effects of morphine and pentazocine: side-effect profiles in healthy adults. Campbell, CM; Fillingim, RB; Glover, TL; Hastie, BA; Riley, JL; Staud, R, 2010)	0.62
" All children were assessed for pain, sedation, time until first oral intake, and adverse effects for 48 h postoperatively."	( Incisional continuous fascia iliaca block provides more effective pain relief and fewer side effects than opioids after pelvic osteotomy in children. Gardeniers, J; Lako, SJ; Staals, LM; Steegers, MA; van Egmond, J; van Geffen, GJ, 2009)	0.35
"31), WOMAC change-from-baseline (mean pain, physical function, composite scores), and adverse event frequency were similar."	( ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules in the treatment of chronic pain of osteoarthritis of the hip or knee: pharmacokinetics, efficacy, and safety. Johnson, F; Katz, N; Stauffer, J; Sun, S, 2010)	0.79
" Discontinuation rates and the incidence of adverse events were also evaluated."	( Efficacy and safety of fentanyl HCl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management for patient subgroups. Anker-Møller, E; Coluzzi, F; Mattia, C; Sonnino, D, 2010)	0.59
" Rates of patient withdrawals and the incidence of adverse events were generally similar between treatment groups in the patient subgroups."	( Efficacy and safety of fentanyl HCl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management for patient subgroups. Anker-Møller, E; Coluzzi, F; Mattia, C; Sonnino, D, 2010)	0.59
" A priori-defined adverse events included out-of-hospital events: respiratory rate <12 breaths/min, pulse oximetry <92%, systolic blood pressure <90 mmHg, any fall in Glasgow Coma Scale score, nausea or vomiting, intubation, and use of antiemetic agents or naloxone."	( Effectiveness and safety of fentanyl compared with morphine for out-of-hospital analgesia. Daya, M; Fleischman, RJ; Frazer, DG; Jui, J; Newgard, CD, )	0.38
" Both medications had low rates of adverse events, which were easily controlled."	( Effectiveness and safety of fentanyl compared with morphine for out-of-hospital analgesia. Daya, M; Fleischman, RJ; Frazer, DG; Jui, J; Newgard, CD, )	0.38
" Outcome measures included pain control and adverse events."	( Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting. Bowen-Roberts, T; Ou, C; Purdy, R; Steinbok, P; Warren, DT, 2010)	0.64
" There were no other significant adverse events."	( Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting. Bowen-Roberts, T; Ou, C; Purdy, R; Steinbok, P; Warren, DT, 2010)	0.64
" We recommend the use of CMIs as an alternative when pain is poorly controlled in post-operative pediatric neurosurgical patients to prevent the potential adverse consequences of inadequate analgesia."	( Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting. Bowen-Roberts, T; Ou, C; Purdy, R; Steinbok, P; Warren, DT, 2010)	0.64
"To determine which class of non-opioid analgesics - paracetamol (acetaminophen), NSAIDs or COX-2 inhibitors - is the most effective at reducing morphine consumption and associated adverse effects when used as part of multimodal analgesia following major surgery."	( Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review. Jenkins, B; Maund, E; McDaid, C; Rice, S; Woolacott, N; Wright, K, 2010)	0.77
" Other outcomes of interest were morphine-related adverse effects and adverse effects related to the non-opioids."	( Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review. Jenkins, B; Maund, E; McDaid, C; Rice, S; Woolacott, N; Wright, K, 2010)	0.85
"We performed a systematic review to assess the analgesic efficacy and the incidence of adverse effects of epidural morphine after caesarean section compared to systemic analgesia with opioids."	( Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Bonnet, MP; Marret, E; Mazoit, JX; Mignon, A; Ozier, Y, 2010)	0.82
" Prospective randomized studies comparing analgesic efficacy and/or adverse effects of a single epidural morphine administration versus systemic opioids after elective caesarean section were included."	( Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Bonnet, MP; Marret, E; Mazoit, JX; Mignon, A; Ozier, Y, 2010)	0.83
" Safety was evaluated according to the number of adverse events and their severity."	( Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain. Cruto, M; Debernardi, F; Massucco, P; Moselli, NM; Savojardo, M, 2010)	0.59
"1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects."	( Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain. Cruto, M; Debernardi, F; Massucco, P; Moselli, NM; Savojardo, M, 2010)	0.59
" The adverse events were as expected in an opioid-treated cancer population and showed no differences between ADPREM and CRM."	( Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory cr Andersen, C; Burneckis, A; Jespersen, L; Ridgway, D; Sopata, M, 2010)	0.58
" Per-operative preparations and management were all standardised, with other drugs being only administered to manage anxiety, pain, nausea/vomiting, hypotension, and any adverse event."	( Spinal anaesthesia for laparoscopic cholecystectomy: a feasibility and safety study. Gautam, B, )	0.13
"Spinal anaesthesia with Morphine-mixed hyperbaric Bupivacaine is adequate and safe for elective LC in otherwise healthy patients and minimises postoperative pain and opioid use."	( Spinal anaesthesia for laparoscopic cholecystectomy: a feasibility and safety study. Gautam, B, )	0.44
"Previous meta-analysis suggested that transdermal fentanyl was not inferior to sustained-release oral morphine in treating moderate-severe cancer pain with less adverse effects."	( Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis. Bi, ZF; Chen, DL; Jiang, ZM; Ma, W; Xie, DR; Yang, Q; Zhang, YD, 2010)	0.8
" Primary end points assessed by meta-analysis were remission rate of pain and incidence of adverse effects."	( Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis. Bi, ZF; Chen, DL; Jiang, ZM; Ma, W; Xie, DR; Yang, Q; Zhang, YD, 2010)	0.59
"Our study showed again that both transdermal fentanyl and oral morphine had the same efficacy in the treatment of moderate-severe cancer pain in Chinese population, but the former might have less adverse effects and better quality of life."	( Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis. Bi, ZF; Chen, DL; Jiang, ZM; Ma, W; Xie, DR; Yang, Q; Zhang, YD, 2010)	0.83
"The analgesic and side effect potential of morphine was compared between wild-type and tac1 null mutant mice."	( Increased morphine analgesia and reduced side effects in mice lacking the tac1 gene. Berner, J; Bilkei-Gorzo, A; Racz, I; Wickström, R; Zimmer, A; Zimmermann, J, 2010)	1.03
" Interestingly, the most serious side effect of acute morphine, that is respiratory depression, was reduced in tac1(-/-) animals."	( Increased morphine analgesia and reduced side effects in mice lacking the tac1 gene. Berner, J; Bilkei-Gorzo, A; Racz, I; Wickström, R; Zimmer, A; Zimmermann, J, 2010)	1.01
" We aimed to determine the adverse events during neonatal intubation using the most commonly used premedication regimen in the UK."	( Endotracheal intubation in a neonatal population remains associated with a high risk of adverse events. Anandaraj, J; Arasu, A; Chaudhary, R; Clarke, P; Curley, A; Malviya, M; Ponnusamy, V; Venkatesh, V, 2011)	0.37
"Safety assessments included determining adverse events (AEs), laboratory assessments, and the Clinical Opiate Withdrawal Scale (COWS)."	( Long-term safety and efficacy of morphine sulfate and naltrexone hydrochloride extended release capsules, a novel formulation containing morphine and sequestered naltrexone, in patients with chronic, moderate to severe pain. Brewer, R; Johnson, FK; Morris, D; Sekora, D; Stauffer, J; Wang, C; Webster, LR, 2010)	0.64
" By comparing the growth and evolution amongst each egg in the group under experiment, after injection, the eggs did not show any adverse reaction after inoculation with therapeutic human morphine vaccine."	( Safety of human therapeutic morphine vaccine employing Lohmann specific pathogen free eggs. Akbarzadeh, A; Bashar, R; Chiani, M; Farhangi, A; Ghassemi, S; Kheiri, M; Mehrabi, MR; Saffari, Z, 2010)	0.85
" Knowing that morphine provides comparable to even prolonged pain reduction after ACL reconstruction, the presented in vitro study suggests morphine as a potentially less toxic analgetic drug for intraarticular application in clinical practice."	( Bupivacaine, ropivacaine, and morphine: comparison of toxicity on human hamstring-derived stem/progenitor cells. Docheva, D; Grote, S; Haasters, F; Kohler, J; Mutschler, W; Polzer, H; Prall, WC; Saller, MM; Schieker, M, 2011)	1.02
" There was no significant difference in the incidence of adverse effects between the two drugs."	( The effectiveness and adverse events of morphine versus fentanyl on a physician-staffed helicopter. Cudnik, M; Emerman, CL; Pakiela, J; Smith, DA; Smith, MD; Wang, Y, 2012)	0.65
" There was a 50-75 percent reduction in moderate to severe adverse events (AEs) commonly associated with opioids (ie, nausea, vomiting, and dizziness) in the MoxDuo 6 mg/4 mg group when compared with its morphine-equivalent dose groups."	( Analgesic and adverse effects of a fixed-ratio morphine-oxycodone combination (MoxDuo) in the treatment of postoperative pain. Kelen, R; Richards, P; Riff, D; Stern, W, )	0.58
" No serious adverse effects associated with bowel stimulation were reported."	( Safety and efficacy of immediate postoperative feeding and bowel stimulation to prevent ileus after major gynecologic surgical procedures. Fanning, J; Hojat, R, 2011)	0.37
"Immediate postoperative feeding and bowel stimulation is a safe and effective approach to preventing ileus in patients who undergo major gynecologic surgical procedures."	( Safety and efficacy of immediate postoperative feeding and bowel stimulation to prevent ileus after major gynecologic surgical procedures. Fanning, J; Hojat, R, 2011)	0.37
" Early detection of respiratory depression is essential for safe use of morphine, following both initial and repeated doses."	( Improved practices for safe administration of intravenous bolus morphine in a pediatric setting. Ellis, J; Gaboury, I; Lamontagne, C; Martelli, B; Pascuet, E; Taillefer, L; Vaillancourt, R, 2011)	0.84
" Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments."	( Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study. Davies, A; Fallon, M; Galvez, R; Kumar, K; Lux, AE; Reale, C; Stachowiak, A, )	0.36
" We conclude that adding low-dose ketamine to morphine PCA is safe and post-thoracotomy may provide better pain control than PCA with morphine alone (PCA-MO), with reduced morphine consumption and possible improvement in respiratory function."	( Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain? Churchhouse, AM; Dunning, J; Housden, T; Mathews, TJ, 2012)	0.94
" However, during cesarean section with neuraxial block, S-Ketamine might have adverse effects on the interaction between mothers and infants, including breastfeeding."	( A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Catarci, S; Draisci, G; Suppa, E; Valente, A; Zanfini, BA, 2012)	0.38
" All side effects were rated as light and there were no serious adverse events."	( A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Catarci, S; Draisci, G; Suppa, E; Valente, A; Zanfini, BA, 2012)	0.38
"Preventive administration of S-Ketamine via 12-hour infusion was safe and may have anti-hyperalgesic action after cesarean section."	( A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Catarci, S; Draisci, G; Suppa, E; Valente, A; Zanfini, BA, 2012)	0.38
"Although opioids are widely accepted as standard therapy for treating acute postoperative pain, the frequent occurrence of adverse events (AEs) and the substantial burden on the patient and the costs of care are a barrier to optimal dosing and adherence to prescribed treatment."	( Efficacy and safety of dual-opioid therapy in acute pain. Webster, L, 2012)	0.38
"The findings indicate comparability of transdermal buprenorphine and transdermal fentanyl for pain measures with significantly fewer adverse events (nausea and treatment discontinuation due to adverse events) caused by transdermal buprenorphine."	( Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain. Aune, D; Hernandez, AV; Kleijnen, J; Misso, K; Riemsma, R; Truyers, C; Wolff, RF, 2012)	0.61
" Statistically significant differences in the occurrence of side effects were documented: While 58% of L children experienced at least one side effect only 20% of NL did (P = 0."	( Is ethnicity associated with morphine's side effects in children? Morphine pharmacokinetics, analgesic response, and side effects in children having tonsillectomy. Anderson, GD; Farin, FM; Jimenez, N; Lynn, AM; Nielsen, SS; Seidel, K; Shen, DD, 2012)	0.67
"It has been confirmed by several clinical trials that the fentanyl patch causes less adverse events than sustained-release oral morphine, and after rotation."	( [A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer]. Fujii, S; Ikeda, M; Koike, Y; Kubo, S; Kurebayashi, J; Mizutou, A; Nakashima, K; Nomura, T; Oota, Y; Saitou, W; Seki, M; Shiiki, S; Shimo, T; Sonoo, H; Tanaka, K; Yamamoto, Y; Yamashita, T, 2012)	0.82
"We prospectively investigated the reduced effects of adverse events caused by sustained-release oral morphine and controlled-release oxycodone after rotating to the fentanyl patch in patients with metastatic breast cancer."	( [A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer]. Fujii, S; Ikeda, M; Koike, Y; Kubo, S; Kurebayashi, J; Mizutou, A; Nakashima, K; Nomura, T; Oota, Y; Saitou, W; Seki, M; Shiiki, S; Shimo, T; Sonoo, H; Tanaka, K; Yamamoto, Y; Yamashita, T, 2012)	0.83
" Those experiencing adverse events from oral morphine or oral oxycodone were administered a fentanyl patch."	( [A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer]. Fujii, S; Ikeda, M; Koike, Y; Kubo, S; Kurebayashi, J; Mizutou, A; Nakashima, K; Nomura, T; Oota, Y; Saitou, W; Seki, M; Shiiki, S; Shimo, T; Sonoo, H; Tanaka, K; Yamamoto, Y; Yamashita, T, 2012)	0.87
"This study suggested that the fentanyl patch can reduce adverse events caused by sustained-release oral morphine as well as controlled-release oral oxycodone."	( [A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer]. Fujii, S; Ikeda, M; Koike, Y; Kubo, S; Kurebayashi, J; Mizutou, A; Nakashima, K; Nomura, T; Oota, Y; Saitou, W; Seki, M; Shiiki, S; Shimo, T; Sonoo, H; Tanaka, K; Yamamoto, Y; Yamashita, T, 2012)	0.83
"Prospective observational study evaluating effect of race on analgesia and opioid related adverse effects after tonsillectomy in African American and Caucasian children."	( Race and unequal burden of perioperative pain and opioid related adverse effects in children. Chidambaran, V; Esslinger, HR; Martin, LJ; McAuliffe, J; Ngamprasertwong, P; Prows, C; Sadhasivam, S; Zhang, X, 2012)	0.38
" Although Caucasian children received relatively less opioids perioperatively, they had significantly higher opioid related adverse effects (P = ."	( Race and unequal burden of perioperative pain and opioid related adverse effects in children. Chidambaran, V; Esslinger, HR; Martin, LJ; McAuliffe, J; Ngamprasertwong, P; Prows, C; Sadhasivam, S; Zhang, X, 2012)	0.38
"After similar uses of intraoperative morphine for tonsillectomy, there was an unequal burden of increased pain in African American children and increased opioid adverse effects in Caucasian children in the recovery room."	( Race and unequal burden of perioperative pain and opioid related adverse effects in children. Chidambaran, V; Esslinger, HR; Martin, LJ; McAuliffe, J; Ngamprasertwong, P; Prows, C; Sadhasivam, S; Zhang, X, 2012)	0.65
"To review postmarketing adverse event (AE) reports received during first year following approval."	( Safety of EMBEda (morphine sulfate and naltrexone hydrochloride) extended-release capsules: review of postmarketing adverse events during the first year. Badalamenti, VC; Buckley, JW; Smith, ET, )	0.47
"Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support."	( Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease*. Gossett, JM; Gupta, P; Roth, SJ; Sabati, A; Tesoro, TM; Tobias, JD; Whiteside, W, 2012)	0.38
" In this patient, this rare side effect decisively impaired life quality, subjectively outweighing the considerable pain relief which could be achieved after formerly inefficacious treatment."	( Erectile dysfunction as rare side effect in the simultaneous intrathecal application of morphine and clonidine. Alfieri, A; Koman, G; Rachingter, J; Scheller, C; Strauss, C, )	0.35
" Moderate to severe gastrointestinal adverse events occurred in 50% of patients in the oxycodone/acetaminophen group compared with 15% of the equianalgesic morphine/oxycodone group."	( Comparison of the efficacy and safety of dual-opioid treatment with morphine plus oxycodone versus oxycodone/acetaminophen for moderate to severe acute pain after total knee arthroplasty. Gimbel, JS; Kelen, R; Minkowitz, HS; Richards, P; Stern, W, 2013)	0.82
"While opioids are potent analgesics widely used in the management of pain, a number of well-known adverse effects limit their use."	( Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects. Baeyens, JM; Bura, SA; Buschmann, H; Codony, X; de la Puente, B; Fernández-Pastor, B; Maldonado, R; Merlos, M; Rocasalbas, M; Romero, L; Touriño, C; Vela, JM; Vidal-Torres, A; Zamanillo, D, 2013)	0.39
"Pruritus is a frequent adverse event after administration of morphine."	( Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials. Du, BX; Shi, XY; Song, ZM; Wang, K; Xu, FY; Zhang, H; Zou, Z, 2013)	0.95
" The frequency of analgesic use and the occurrence of adverse side effects during the first 48 hours after surgery were compared between the two groups."	( [Safety and beneficial effects of spinal morphine on the postoperative course of elderly patients undergoing surgical fixation of the femoral neck fracture]. Baba, H; Fujiwara, T; Mochida, T; Watanabe, I; Watanabe, T, 2013)	0.66
"1 mg morphine had beneficial effects and was safe in the postoperative period of elderly patients with femoral neck fracture provided that sufficient observation was given."	( [Safety and beneficial effects of spinal morphine on the postoperative course of elderly patients undergoing surgical fixation of the femoral neck fracture]. Baba, H; Fujiwara, T; Mochida, T; Watanabe, I; Watanabe, T, 2013)	1.17
"Low-dosage misoprostol required more time than dinoprostone to induce labour, but the two drugs were equally safe in terms of the risk of caesarean section and foetal outcomes."	( Safe induction of labour with low-dose misoprostol, but less effective than the conventional dinoprostone regimen. Bergholt, T; Løkkegaard, EC; Petersen, JF, 2013)	0.39
"IV-PCA provided timely, safe and useful analgesia for patients with severe breakthrough pain and may be useful to help titration of opioids, weaning to oral analgesia and to decide for interventional procedures."	( Safety profile of intravenous patient-controlled analgesia for breakthrough pain in cancer patients: a case series study. Ashmawi, HA; Cascudo, GM; de Santana Neto, J; Guimaraes, GM; Neto, JO; Sousa, AM, 2014)	0.4
"Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis."	( Activation of TREK-1 by morphine results in analgesia without adverse side effects. Alloui, A; Busserolles, J; Christin, M; Delmas, P; Deval, E; Devilliers, M; Eschalier, A; Lazdunski, M; Lolignier, S; Mazet, B; Noel, J; Pereira, V, 2013)	2.14
"Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use."	( Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice. Ferreira, J; Gewehr, C; Gomez, MV; Pereira, EM; Rigo, F; Tonello, R; Trevisan, G, 2014)	0.61
" Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine."	( Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice. Ferreira, J; Gewehr, C; Gomez, MV; Pereira, EM; Rigo, F; Tonello, R; Trevisan, G, 2014)	0.84
" This secondary analysis evaluated whether endogenous opioid activity is associated with degree of opioid analgesic adverse effects, and whether chronic pain status and sex affect these adverse effects."	( Relationship between endogenous opioid function and opioid analgesic adverse effects. Bruehl, S; Burns, JW; Buvanendran, A; Chont, M; France, CR; Gupta, RK; Schuster, E, )	0.13
" These measures were examined for associations with morphine-related adverse effects."	( Relationship between endogenous opioid function and opioid analgesic adverse effects. Bruehl, S; Burns, JW; Buvanendran, A; Chont, M; France, CR; Gupta, RK; Schuster, E, )	0.38
" Across groups, only 6 of 112 possible associations between adverse effects and blockade effects were significant."	( Relationship between endogenous opioid function and opioid analgesic adverse effects. Bruehl, S; Burns, JW; Buvanendran, A; Chont, M; France, CR; Gupta, RK; Schuster, E, )	0.13
"No consistent relationships were observed between endogenous opioid function and morphine-related adverse effects."	( Relationship between endogenous opioid function and opioid analgesic adverse effects. Bruehl, S; Burns, JW; Buvanendran, A; Chont, M; France, CR; Gupta, RK; Schuster, E, )	0.36
"With the exception of one severe adverse event (AE), all others were mild or moderate in intensity."	( Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants. Johnson, F; Oldenhof, J; Romach, M; Setnik, B; Sokolowska, M, 2014)	0.61
"Opioids provide powerful analgesia but also efficacy-limiting adverse effects, including severe nausea, vomiting, and respiratory depression, by activating μ-opioid receptors."	( Biased agonism of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Burnham, N; James, IE; Lark, MW; Sadler, BM; Skobieranda, F; Soergel, DG; Subach, RA; Violin, JD; Webster, LR, 2014)	0.61
"It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects."	( Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects. Benneyworth, MA; Kalyuzhny, AE; Le Naour, M; Lunzer, MM; Portoghese, PS; Powers, MD; Thomas, MJ, 2014)	0.4
"Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs)."	( Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence. Babic-Hohnjec, L; Berthel, T; Bonorden-Kleij, K; Gholami, N; Haasen, C; Hämmig, R; Höpner, D; Köhler, W; Lebentrau, K; Reimer, J; Ruckes, C; Verthein, U; Vollmert, C; Weber, B, 2014)	0.66
"Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy."	( Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. Chey, WD; Diva, U; Lappalainen, J; Sostek, M; Tack, J; Webster, L, 2014)	0.4
" Frequency of adverse events (AEs) was 81."	( Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. Chey, WD; Diva, U; Lappalainen, J; Sostek, M; Tack, J; Webster, L, 2014)	0.4
"In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated."	( Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. Chey, WD; Diva, U; Lappalainen, J; Sostek, M; Tack, J; Webster, L, 2014)	0.4
" Adverse reactions were observed in 17."	( Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain. Gomyo, I; Higuchi, H; Kojima, K; Ohta, E; Shimoyama, M; Shimoyama, N; Teramoto, O; Yukitoshi, N, 2015)	0.63
"Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects."	( Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids. Chidambaran, V; Clay, S; Costandi, A; Martin, LJ; Olbrecht, VA; Prows, CA; Sadhasivam, S; Zhang, X, 2015)	0.42
" Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects."	( Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids. Chidambaran, V; Clay, S; Costandi, A; Martin, LJ; Olbrecht, VA; Prows, CA; Sadhasivam, S; Zhang, X, 2015)	0.42
"This study demonstrates that child's sex influences morphine's dose response and adverse effects."	( Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids. Chidambaran, V; Clay, S; Costandi, A; Martin, LJ; Olbrecht, VA; Prows, CA; Sadhasivam, S; Zhang, X, 2015)	0.67
" The primary outcome measure was the decrements in morphine dose; secondary outcomes included quantitative assessments of sleep (rated according to the Medical Outcomes Study Sleep Scale), the Constipation Assessment Scale and adverse effects."	( Efficacy and safety of pregabalin in patients with neuropathic cancer pain undergoing morphine therapy. Dou, Z; Jiang, Z; Zhong, J, 2017)	0.93
"PGB enhances the efficacy of oral morphine and reduces dose-related adverse reactions."	( Efficacy and safety of pregabalin in patients with neuropathic cancer pain undergoing morphine therapy. Dou, Z; Jiang, Z; Zhong, J, 2017)	0.96
" Taking into account the high consumption of codeine, only few fatal adverse events have been published."	( Codeine Ultra-rapid Metabolizers: Age Appears to be a Key Factor in Adverse Effects of Codeine. Fuchs, W; Heintze, K, 2015)	0.42
"Potentially severe and clinically relevant adverse events (AEs) associated with IT morphine include respiratory depression, tolerance, and granuloma formulation, whereas IT ziconotide is associated with neuropsychiatric AEs, such as cognitive impairment, hallucinations, and changes in mood or consciousness, particularly with high doses and rapid titration."	( The Relationship Between the Mechanisms of Action and Safety Profiles of Intrathecal Morphine and Ziconotide: A Review of the Literature. Webster, LR, 2015)	0.87
" The primary outcome was the percentage of patients without adverse event-related study discontinuations who presented with a combination of a ≥50% improvement of pain intensity, disability and quality-of-life and a ≤50% worsening of bowel function at study end."	( Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine for the treatment of chronic low back pain: results of a 12 week prospective, randomized, open-label blinded endpoint streamlined study with prolonged-release preparations. Mueller-Schwefe, GH; Ueberall, MA, 2015)	0.66
" Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as used and titrated in routine cancer pain care."	( Renal function and symptoms/adverse effects in opioid-treated patients with cancer. Christrup, L; Dale, O; Davies, A; Ekholm, O; Kaasa, S; Klepstad, P; Kurita, GP; Lundström, S; Sjøgren, P, 2015)	0.42
"Although morphine is the standard opioid analgesic for pain control and has been widely used, certain drug-induced adverse effects have been reported as intolerable and need to be addressed."	( A comparision of nalbuphine with morphine for analgesic effects and safety : meta-analysis of randomized controlled trials. Chen, Y; Guo, T; Lu, J; Shu, C; Wu, QP; Yao, SL; Yin, P; Zeng, Z, 2015)	1.12
"Use of intrathecal admixtures is widespread, but compounding these is sometimes challenging and may result in errors and complications causing super-potency or sub potency adverse events in patients or malfunctions in the pump itself."	( Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine, Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in Clinical Practice. Bazin, C; Boré, F; Devys, C; Dubois, PY; Dupoiron, D; Folliard, C; Kieffer, H; Lebrec, N, )	0.37
"This study is monocentric and limitations include also its non-randomized nature with no clinical comparison of the rate of adverse events with a refill process without control of each component concentrations."	( Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine, Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in Clinical Practice. Bazin, C; Boré, F; Devys, C; Dubois, PY; Dupoiron, D; Folliard, C; Kieffer, H; Lebrec, N, )	0.37
"This analysis compared opioid-related adverse events (ORADEs) observed with fentanyl iontophoretic transdermal system (ITS) versus morphine intravenous (iv."	( A comparison of opioid-related adverse events with fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in acute postoperative pain. Danesi, H; Ding, L; Grond, S; Jones, JB; Sinatra, RS; Viscusi, ER, 2016)	0.85
" Treatment-emergent adverse events were collected via spontaneous report."	( A comparison of opioid-related adverse events with fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in acute postoperative pain. Danesi, H; Ding, L; Grond, S; Jones, JB; Sinatra, RS; Viscusi, ER, 2016)	0.65
"The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment."	( Oral Sedation Postdischarge Adverse Events in Pediatric Dental Patients. Huang, A; Tanbonliong, T, 2015)	0.42
"Although intrathecal drug infusion has been commonly adopted for terminal cancer pain relief, its adverse effects have made many clinicians reluctant to employ it for intractable cancer pain."	( Efficacy and Safety of Ropivacaine Addition to Intrathecal Morphine for Pain Management in Intractable Cancer. Huang, Y; Li, X; Lin, J; Tao, G; Zhu, T, 2015)	0.66
" Adverse effects and complications on postoperative days 1, 3, 7, and 15 were also analyzed."	( Efficacy and Safety of Ropivacaine Addition to Intrathecal Morphine for Pain Management in Intractable Cancer. Huang, Y; Li, X; Lin, J; Tao, G; Zhu, T, 2015)	0.66
"Morphine and ropivacaine administration through intrathecal access ports is efficacious and safe and significantly improves quality of life."	( Efficacy and Safety of Ropivacaine Addition to Intrathecal Morphine for Pain Management in Intractable Cancer. Huang, Y; Li, X; Lin, J; Tao, G; Zhu, T, 2015)	2.1
" We observed a significant reduction in morphine adverse effects (31% versus 69% for groups R and P, respectively; P<0."	( Impact of preoperative continuous femoral blockades on morphine consumption and morphine side effects in hip-fracture patients: A randomized, placebo-controlled study. Bouhours, G; Chaudet, A; Hamel, JF; Lasocki, S; Leblanc, D; Rineau, E; Steiger, V, 2016)	0.95
"Subgroup analysis of patients aged ≥65 years and <65 years was performed on pooled data for adverse events (AEs), potentially clinically significant laboratory values (hematology/chemistry), and signs/symptoms of opioid withdrawal using the Clinical Opiate Withdrawal Scale (COWS) (phase 3 trials only) for patients who received at least one dose (short-term studies, maximum dose was 160 mg/d or 320 mg/d depending on study; long-term study, no maximum dose) of study medication during titration and maintenance phases."	( Safety profile of extended-release morphine sulfate with sequestered naltrexone hydrochloride in older patients: pooled analysis of three clinical trials. Pixton, GC; Setnik, B; Webster, LR, 2016)	0.71
" The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.68
"Compare with intravenous analgesia, incidence of the adverse reactions of cryoanalgesia is lower, and there is no increasing in the stress response."	( [Analgesic effect and safety of intercostal nerve cryoanalgesia after the video-assisted thoracoscopic surgery]. He, Y; Li, F; Li, W; Li, Y; Lin, H; Wang, J; Xu, M; Ye, S, 2015)	0.42
" Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain."	( A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study. Dirksen, CD; Franssen, FM; Janssen, DJ; Schols, JM; van den Beuken-van Everdingen, MH; Verberkt, CA; Wouters, EF, 2016)	1.57
" Additionally, those patients administered epidural oxycodone had lower pain scores, needed less rescue analgesics and had fewer adverse effects compared with intravenous administration."	( Cytotoxicity of Oxycodone and Morphine in Human Neuroblastoma and Mouse Motoneuronal Cells: A Comparative Approach. Kokki, H; Kokki, M; Litmala, O; Pasanen, M; Pesonen, M; Vehviläinen, P, 2016)	0.72
" At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded."	( Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids. Apolone, G; Azzarello, G; Bandieri, E; Caraceni, A; Cavanna, L; Corli, O; Crispino, C; Di Gregorio, R; Dragani, TA; Floriani, I; Galli, F; Gamucci, T; Greco, MT; Iorno, V; Kaasa, S; Lipari, G; Luzzani, M; Montanari, M; Pacchioni, M; Pavesi, L; Reale, C; Roberto, A; Valenti, D, 2016)	0.43
"The main findings were the similarity in pain control, response rates and main adverse reactions among opioids."	( Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids. Apolone, G; Azzarello, G; Bandieri, E; Caraceni, A; Cavanna, L; Corli, O; Crispino, C; Di Gregorio, R; Dragani, TA; Floriani, I; Galli, F; Gamucci, T; Greco, MT; Iorno, V; Kaasa, S; Lipari, G; Luzzani, M; Montanari, M; Pacchioni, M; Pavesi, L; Reale, C; Roberto, A; Valenti, D, 2016)	0.43
" Acute adverse events in the morphine group occurred in 19 (3%) participants."	( Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial. Afzal, MS; Al Hilli, SA; Al Rumaihi, K; Anjum, S; Cameron, PA; Mitra, B; Morley, K; Pathan, SA; Shukla, D; Straney, LD; Thomas, SH, 2016)	0.73
" The most common adverse events were somnolence, dizziness, headache, and nausea."	( Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending-dose study. Bui, K; Butler, K; Eldon, MA; Kugler, AR; Medve, RA; Sostek, M, 2015)	0.42
"Introduction of standard infusions is safe and effective."	( Safe implementation of standard concentration infusions in paediatric intensive care. Aguado-Lorenzo, V; Arenas-López, S; Calleja-Hernández, MA; Durward, A; Perkins, J; Philip, J; Stanley, IM; Tibby, SM; Tunstell, P, 2017)	0.46
"Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent."	( Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone. Aminian, A; Asadi Amoli, F; Dehpour, AR; Ejtemaei Mehr, S; Javadi, S; Moghaddas, P; Rahimian, R, 2016)	0.7
" Unfortunately, we have shown that morphine administered in the acute phase of SCI results in significant, adverse secondary consequences including compromised locomotor and sensory recovery."	( Nor-Binaltorphimine Blocks the Adverse Effects of Morphine after Spinal Cord Injury. Aceves, AR; Aceves, M; Bancroft, EA; Hook, MA, 2017)	0.99
" The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity."	( Growth hormone is protective against acute methadone-induced toxicity by modulating the NMDA receptor complex. Diwakarla, S; Grönbladh, A; Hallberg, M; Nyberg, F; Nylander, E; Zelleroth, S, 2016)	0.43
" The objective of this study was to elucidate the efficacy and adverse effects of a sub-dissociative dose of IN Ketamine compared to IV and IM morphine."	( Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safety. Gigi, R; Halpern, P; Nadav, D; Rozenek, M; Sarig-Meth, T; Shapira, A; Shimonovich, S; West, D, 2016)	0.64
" Pain relief and adverse effects were recorded for 1 h post-administration."	( Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safety. Gigi, R; Halpern, P; Nadav, D; Rozenek, M; Sarig-Meth, T; Shapira, A; Shimonovich, S; West, D, 2016)	0.43
" Therefore, TAP block is a safe and effective procedure compared to standard care, placebo and other analgesic techniques."	( Clinical safety and effectiveness of transversus abdominis plane (TAP) block in post-operative analgesia: a systematic review and meta-analysis. Cameron, AL; Duncan, JK; Ma, N; Scarfe, AJ; Schuhmann, S, 2017)	0.46
" In addition, fewer adverse side effect was identified in FIB groups (RD = -0."	( The efficiency and safety of fascia iliaca block for pain control after total joint arthroplasty: A meta-analysis. Li, J; Song, Y; Wang, X; Zhang, P, 2017)	0.46
" In addition, there were fewer adverse effects in FIB groups."	( The efficiency and safety of fascia iliaca block for pain control after total joint arthroplasty: A meta-analysis. Li, J; Song, Y; Wang, X; Zhang, P, 2017)	0.46
" There were no serious or life-threatening adverse effects in either group."	( Is Subdissociative Ketamine As Safe and Effective As Morphine for Pain Management in the Emergency Department? Gisness, CM; Howard, PK, )	0.38
"Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events."	( OCT1 genetic variants are associated with postoperative morphine-related adverse effects in children. Balyan, R; Chidambaran, V; Fukuda, T; Martin, LJ; Mizuno, T; Sadhasivam, S; Vinks, AA; Zhang, X, 2017)	0.97
" Pain scores, adverse events, and length of stay were recorded."	( Intrathecal Morphine and Oral Analgesics Provide Safe and Effective Pain Control After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis. Abbott, MD; Burke, MC; Caird, MS; Farley, FA; Gibbons, KM; Holman, AE; Hong, RA; Li, Y; Robbins, CB, 2018)	0.86
" Adverse events occurred at similar rates in both groups."	( Intrathecal Morphine and Oral Analgesics Provide Safe and Effective Pain Control After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis. Abbott, MD; Burke, MC; Caird, MS; Farley, FA; Gibbons, KM; Holman, AE; Hong, RA; Li, Y; Robbins, CB, 2018)	0.86
"ITM and oral analgesics provide safe and effective pain control after PSF for AIS."	( Intrathecal Morphine and Oral Analgesics Provide Safe and Effective Pain Control After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis. Abbott, MD; Burke, MC; Caird, MS; Farley, FA; Gibbons, KM; Holman, AE; Hong, RA; Li, Y; Robbins, CB, 2018)	0.86
" The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction."	( Polyglycerol-opioid conjugate produces analgesia devoid of side effects. González-Rodríguez, S; Gupta, S; Haag, R; Joseph, J; Labuz, D; Machelska, H; Parr, MK; Quadir, MA; Rodriguez-Gaztelumendi, A; Schmelz, M; Spahn, V; Stein, C; Walker, KA; Zhang, X, 2017)	0.46
"Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine."	( A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide treatment for postpartum pain and avert infant adverse events. Berger, H; Ito, S; Koren, G; Lato, DF; Moretti, ME; Ungar, WJ, 2018)	0.67
" No severe adverse effects associated with continuous wound infiltration were observed during the study period."	( Efficacy and Safety of a Continuous Wound Catheter in Open Abdominal Partial Hepatectomy. Che, L; Lu, X; Pei, LJ, 2017)	0.46
" However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects."	( Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis. Datla, S; Dirksen, CD; Janssen, DJA; Johnson, MJ; Schols, JMGA; van den Beuken-van Everdingen, MHJ; van Kuijk, SMJ; Verberkt, CA; Wouters, EFM, 2017)	0.46
" Horses were monitored for adverse ocular and systemic effects throughout the study period."	( Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye. Cebra, CK; Gordon, E; Heidel, J; Poulsen, KP; Schlipf, JW; Stang, BV, 2018)	0.73
"0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects."	( Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye. Cebra, CK; Gordon, E; Heidel, J; Poulsen, KP; Schlipf, JW; Stang, BV, 2018)	1.35
" The primary outcomes were associations between the use of different premedication regimens with number of TI attempts, TI adverse events (TIAEs), and changes in heart rate."	( Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. Gray, M; Krick, J; Lee, G; Sawyer, T; Umoren, R, 2018)	0.48
" Specific patient populations which significantly struggle with adverse outcomes related to opioid abuse are seen in palliative care, chronic pain, and acute pain treatment settings."	( Labeling Morphine Milligram Equivalents on Opioid Packaging: a Potential Patient Safety Intervention. Grant, MC; Kaye, AD; Stone, AB; Urman, RD, 2018)	0.9
" Therefore circumventing the side effects, such as euphoria, addiction, respiratory depression and gastrointestinal adverse reactions, is of extensive importance."	( Novel Opioid Receptor Agonists with Reduced Morphine-like Side Effects. Cui, Z; Xu, Y; Zha, X; Zhu, L; Zhu, Q, 2018)	0.74
" Massive tumour cell lysis during the course of chemotherapy may precipitate tumour lysis syndrome and may lead to renal dysfunction which makes the patient susceptible to morphine-related adverse effects."	( Opioid toxicity with underlying tumour lysis syndrome in a patient with CMML: a diagnostic and therapeutic challenge. Bhan, S; Mishra, S; Rustagi, K; Vig, S, 2018)	0.67
" Our results in nonhuman primates suggest that bifunctional NOP/MOP agonists with the appropriate balance of NOP and MOP agonist activity may provide a dual therapeutic action for safe and effective pain relief and treating prescription opioid abuse."	( A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates. Czoty, PW; Daga, PR; Ding, H; Kiguchi, N; Kishioka, S; Ko, MC; Lu, JJ; Polgar, WE; Yasuda, D; Zaveri, NT, 2018)	0.48
" We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain."	( Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Adams, E; Bell, JL; Buckle, M; Goksan, S; Green, G; Gursul, D; Hartley, C; Hoskin, A; Juszczak, E; King, AR; Monk, V; Moultrie, F; Norman, JE; Patel, C; Rogers, R; Slater, R; van der Vaart, M, 2018)	1.04
" The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy."	( Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Adams, E; Bell, JL; Buckle, M; Goksan, S; Green, G; Gursul, D; Hartley, C; Hoskin, A; Juszczak, E; King, AR; Monk, V; Moultrie, F; Norman, JE; Patel, C; Rogers, R; Slater, R; van der Vaart, M, 2018)	0.97
" Surprisingly, respiratory depression, constipation, and opioid withdrawal signs are unchanged or exacerbated, indicating that β-arrestin recruitment does not contribute to the severity of opioid side effects and, hence, predicting that G-protein-biased µ-agonists are still likely to elicit severe adverse effects."	( Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects. Bailey, A; Bateman, JT; Christie, MJ; Kliewer, A; Levitt, ES; Schmiedel, F; Schulz, S; Sianati, S; Williams, JT, 2019)	0.51
" Here, we thus hypothesized that the combined use of opioid and NT agonists would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced adverse effects."	( The combination of opioid and neurotensin receptor agonists improves their analgesic/adverse effect ratio. Blais, V; Côté, J; Eiselt, E; Gendron, L; Longpré, JM; Sarret, P, 2019)	0.51
" However, although opioids have been appropriately used in Japan, they rarely induce serious adverse events, such as respiratory depression."	( Current Status of Adverse Events Related with Opioid Analgesics in Japan: Assessment Based on Japanese Adverse Drug Event Report Database. Futamura, A; Nakagawa, T; Suga, Y; Sugawara, H; Suzuki, S; Takase, H; Torigoe, K; Uchida, M; Uesawa, Y, 2019)	0.51
" With regards to adverse effects, it did not increase the risk of postoperative infection, postoperative nausea and vomiting (PONV), or other complications."	( The efficiency and safety of steroid addition to multimodal cocktail periarticular injection in knee joint arthroplasty: a meta-analysis of randomized controlled trials. Deng, Z; Gao, S; Kotian, RN; Lei, G; Li, Y; Lu, W; Storm, GR; Sun, X, 2019)	0.51
" Generally, meloxicam IV was well tolerated, evidenced by the incidence of adverse events compared to placebo and lack of deaths and treatment-related serious adverse events."	( Analgesic Efficacy and Safety of Intravenous Meloxicam in Subjects With Moderate-to-Severe Pain After Open Abdominal Hysterectomy: A Phase 2 Randomized Clinical Trial. Du, W; Freyer, A; Mack, RJ; McCallum, SW; Rechberger, T, 2019)	0.51
" The mild or moderate adverse effects were similar in 2 groups, while severe adverse effects were only identified in morphine group (P = ."	( Efficacy and safety of sustained-release oxycodone compared with immediate-release morphine for pain titration in cancer patients: A multicenter, open-label, randomized controlled trial (SOCIAL). Guo, Q; Han, F; Lu, L; Pan, H; Pan, J; Qian, S; Shen, P; Shu, Q; Wang, K; Xu, Q; Yang, Z; Zhang, P; Zhou, Y, 2019)	0.95
" Although traditional opioids are the most effective painkillers, they are accompanied by severe adverse responses, such as respiratory depression, constipation symptoms, tolerance, withdrawal, and addiction."	( BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine. Chang, HF; Chang, WT; Chao, PK; Chuang, JY; Loh, HH; Ou, LC; Shih, C; Tao, PL; Tsu-An Hsu, J; Ueng, SH; Yeh, SH; Yeh, TK, 2020)	0.76
"Data (ie, pain intensity, morphine consumption, gastrointestinal and psychotic adverse effects) were extracted by two reviewers independently."	( Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies. Ding, X; He, H; Lei, G; Li, J; Wang, Y; Wei, J; Wu, Z; Xie, D; Xu, B; Zeng, C, 2019)	0.81
"001; four studies, 252 participants) postoperative periods, without increasing risks of gastrointestinal or psychotic adverse effects."	( Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies. Ding, X; He, H; Lei, G; Li, J; Wang, Y; Wei, J; Wu, Z; Xie, D; Xu, B; Zeng, C, 2019)	0.51
"Intravenous administration of ketamine is effective and safe for postoperative pain relief in patients undergoing total knee or hip arthroplasty."	( Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies. Ding, X; He, H; Lei, G; Li, J; Wang, Y; Wei, J; Wu, Z; Xie, D; Xu, B; Zeng, C, 2019)	0.51
"Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs)."	( Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden. Habib, AS; Iqbal, SU; Kugel, M; Liu, S; Morland, K; Oderda, GM; Senagore, AJ, )	0.13
" Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients."	( Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA). Bonafede, E; Carpinteri, G; Fabbri, A; Farina, A; Gangitano, G; Intelligente, F; Mercadante, S; Ruggiano, G; Sblendido, A; Serra, S; Soldi, A; Voza, A, 2019)	0.51
" Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures."	( Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events. Hooten, WM; Jeffery, MM; Larochelle, M; Meara, E; Morden, NE; Shah, ND, 2020)	0.82
" Adverse events were rare and not significantly different in exposed versus unexposed groups."	( Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events. Hooten, WM; Jeffery, MM; Larochelle, M; Meara, E; Morden, NE; Shah, ND, 2020)	0.56
" Several studies have suggested opioid antagonist and antioxidant therapy for reducing adverse effects of morphine."	( Behavioral, histopathological, and biochemical evaluations on the effects of cinnamaldehyde, naloxone, and their combination in morphine-induced cerebellar toxicity. Farshid, AA; Imani, M; Mahmoudi, S; Noroozinia, F; Tamaddonfard, E, 2022)	1.14
" There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo."	( Opioids for chronic non-cancer neuropathic pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration. Häuser, W; Klose, P; Petzke, F; Sommer, C; Welsch, P, 2020)	0.56
"Prolonged use of opioids causes analgesic tolerance and adverse effects including constipation and dependence."	( Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models. Bonazzi, A; Borsi Franchini, M; Caselli, G; Comi, E; Ferrari, F; Lanza, M; Milia, C; Rovati, LC; Sabatini, C; Sala, E, 2020)	0.77
" Opioid-induced adverse effects were assessed in rodent models of morphine-induced constipation, sedation (open field, sedation rating scale, and rotarod), physical dependence (naloxone-induced withdrawal), and abuse (conditioned place preference-associated reward)."	( Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models. Bonazzi, A; Borsi Franchini, M; Caselli, G; Comi, E; Ferrari, F; Lanza, M; Milia, C; Rovati, LC; Sabatini, C; Sala, E, 2020)	1.01
"Randomized controlled trials that compared the analgesic efficacy and side effect profile of meperidine versus another analgesic drug in adult patients were evaluated."	( Analgesic Efficacy and Adverse Effects of Meperidine in Managing Postoperative or Labor Pain: A Narrative Review of Randomized Controlled Trials. Cheung, CW; Ching Wong, SS, 2020)	0.56
"Acute postoperative pain, adverse effects, labor analgesia, meperidine, pethidine."	( Analgesic Efficacy and Adverse Effects of Meperidine in Managing Postoperative or Labor Pain: A Narrative Review of Randomized Controlled Trials. Cheung, CW; Ching Wong, SS, 2020)	0.56
" Adverse side effects of lidocaine and morphine sulfate and changes in vital signs were also recorded and compared."	( The efficacy of intravenous lidocaine and its side effects in comparison with intravenous morphine sulfate in patients admitted to the ED with right upper abdominal pain suspected of biliary colic. Akhgar, A; Hossein-Nejad, H; Nejati, A; Pouryousefi, T; Rafiemanesh, H, 2021)	1.11
" Only 9 patients had adverse effects in either group."	( The efficacy of intravenous lidocaine and its side effects in comparison with intravenous morphine sulfate in patients admitted to the ED with right upper abdominal pain suspected of biliary colic. Akhgar, A; Hossein-Nejad, H; Nejati, A; Pouryousefi, T; Rafiemanesh, H, 2021)	0.84
" Evidence for safety is insufficient as comprehensive adverse events were not adequately reported in studies."	( Efficacy and Safety of Opioids in Treating Cancer-Related Dyspnea: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials. Cen, H; Chen, C; Chen, M; Feng, S; Huang, Z; Li, X; Liang, M; Lin, Y; Liu, S; Luo, N; Singh, S; Tan, S, 2021)	0.62
" The purpose of this trial was to compare opioid-related adverse events (ORAES) of intravenous oxycodone and morphine after total hip arthroplasty."	( Post-operative opioid-related adverse events with intravenous oxycodone compared to morphine: A randomized controlled trial. Alonso, S; Boisson, C; Cuvillon, P; Kouyoumdjian, P; L'Hermite, J; Langeron, O; Luc Faillie, J; Raux, M; Reubrecht, V; Vialles, N; Zoric, L, 2021)	1.06
" Secondary outcomes included morphine consumption at 24, 48, and 72 hours after surgery, length of hospital stay, range of motion, daily ambulation distance, and adverse events occurrence."	( Effect and safety of intravenous versus oral acetaminophen after unicompartmental knee replacement: A protocol of randomized controlled study. Guo, D; Li, X; Wang, H; Zhou, T, 2020)	0.85
" However, their risk-benefit ratio is dampened by numerous adverse effects and opioid misuse has led to a public health crisis."	( TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects. Ben Soussia, I; Busserolles, J; Chapuy, E; Clémenceau, L; Devilliers, M; Ducki, S; Eschalier, A; Judon, C; Lesage, F; Lolignier, S; Marie, N; Meleine, M; Noble, F; Pouchol, L; Poupon, L; Richard, S; Schopp, J, 2020)	0.56
"The TREK1 potassium channel is activated downstream of μ receptor and involved in the antinociceptive activity of morphine but not in its adverse effects."	( TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects. Ben Soussia, I; Busserolles, J; Chapuy, E; Clémenceau, L; Devilliers, M; Ducki, S; Eschalier, A; Judon, C; Lesage, F; Lolignier, S; Marie, N; Meleine, M; Noble, F; Pouchol, L; Poupon, L; Richard, S; Schopp, J, 2020)	0.77
"This proof-of-concept study shows that TREK1 activators could constitute a novel class of painkillers, inspired by the mechanism of action of opioids but devoid of their adverse effects."	( TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects. Ben Soussia, I; Busserolles, J; Chapuy, E; Clémenceau, L; Devilliers, M; Ducki, S; Eschalier, A; Judon, C; Lesage, F; Lolignier, S; Marie, N; Meleine, M; Noble, F; Pouchol, L; Poupon, L; Richard, S; Schopp, J, 2020)	0.56
" Postoperative nausea and vomiting, length of hospital stay, patient satisfaction, and other adverse events were also evaluated."	( The efficacy and safety of the infiltration of the interspace between the popliteal artery and the capsule of the knee block in total knee arthroplasty: A prospective randomized trial protocol. Cong, Z; Ma, F; Zhang, L, 2020)	0.56
" Therefore, seeking a safe and effective postoperative analgesia is necessary for promoting the application of arthroscopic surgery."	( Comparative efficacy and safety of intra-articular analgesics after knee arthroscopy: a Bayesian network meta-analysis protocol. He, H; He, Y; Li, X; Wang, Y; Xie, DX, 2020)	0.56
" Moreover, patients will be actively monitored with regard to the occurrence of side effects of evaluated therapies, as well as adverse events that may be related to insufficient platelet inhibition (no-reflow phenomenon assessed immediately after PCI, administration of GPIIb/IIIa inhibitors during PCI, acute stent thrombosis)."	( ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial. Adamski, P; Buszko, K; Gasior, M; Gorący, J; Kleinrok, A; Kosobucka, A; Kubica, A; Kubica, J; Lesiak, M; Nadolny, K; Navarese, E; Niezgoda, P; Wojakowski, W, 2021)	0.9
"Pre-incision IM is a safe adjunct for pain management in select children in all diagnostic groups undergoing spinal deformity surgery."	( The safety and efficacy of intrathecal morphine in pediatric spinal deformity surgery: a 25-year single-center experience. Hardesty, CK; Ina, JG; Poe-Kochert, C; Rubin, K; Son-Hing, JP; Thompson, GH; Tripi, PA, 2021)	0.89
" The risk of pruritis is significantly increased with the use of IT morphine but not for other opioid-related adverse events."	( Efficacy and safety of intrathecal morphine for pain control after spinal surgery: a systematic review and meta-analysis. Sun, H; Sun, HP; Sun, J; Sun, WT; Tian, T; Wang, J, 2021)	1.13
" Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic-mediated adverse effects."	( Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects. Aso, E; Cabré, G; Ciruela, F; De Koninck, Y; Fernández-Dueñas, V; Font, J; Giraldo, J; Hernando, J; Llebaria, A; López-Cano, M; Sahlholm, K, 2023)	1.19
" Administration of acetaminophen plus morphine versus morphine alone did not increase adverse events and a morphine sparing effect of acetaminophen was demonstrated in two studies."	( The efficacy and safety of acetaminophen use following liver resection: a systematic review. Koea, J; Murphy, V; Srinivasa, S, 2022)	0.99
"Use of acetaminophen for adult patients undergoing liver resection surgery as post-operative analgesia at a standard dosage is safe for baseline analgesia."	( The efficacy and safety of acetaminophen use following liver resection: a systematic review. Koea, J; Murphy, V; Srinivasa, S, 2022)	0.72
" The only feared side effect is pruritus."	( Efficacy and safety of intrathecal morphine in total knee arthroplasty: A systematic review and meta-analysis. Abdelghany, EA; AbdelQadir, YH; Elmegeed, AA; Mohamed, AG; Nabhan, AE; Nourelden, AZ; Ragab, KM; Tokhey, ASE, )	0.41
"This study compared the effects of adductor canal blocks with those of a low concentration of popliteal-sciatic nerve block (SNB) and dexamethasone as an adjunctive technique for total knee arthroplasties (TKA) in patients susceptible to the adverse effects of NSAIDs."	( Adding a low-concentration sciatic nerve block to total knee arthroplasty in patients susceptible to the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs): a randomized controlled trial. Halilamien, P; Kerdchan, T; Poolsuppasit, S; Sirivanasandha, B; Sutthivaiyakit, K; Tangwiwat, S, 2021)	0.62
"A prospective, double-blinded, randomized controlled trial was performed in 50 patients susceptible to the adverse effects of NSAIDs undergoing unilateral TKAs."	( Adding a low-concentration sciatic nerve block to total knee arthroplasty in patients susceptible to the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs): a randomized controlled trial. Halilamien, P; Kerdchan, T; Poolsuppasit, S; Sirivanasandha, B; Sutthivaiyakit, K; Tangwiwat, S, 2021)	0.62
"For patients susceptible to the adverse effects of NSAIDs, a low concentration of SNB and dexamethasone is an effective adjunctive technique for early postoperative pain control (especially on movement) following TKAs, without an increase in motor weakness."	( Adding a low-concentration sciatic nerve block to total knee arthroplasty in patients susceptible to the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs): a randomized controlled trial. Halilamien, P; Kerdchan, T; Poolsuppasit, S; Sirivanasandha, B; Sutthivaiyakit, K; Tangwiwat, S, 2021)	0.62
" In silico findings indicate the high toxic potential of etazene which may lead to drug-drug interactions and accumulation of substances."	( Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative. Boguszewska-Czubara, A; Budzyńska, B; Chłopaś-Konowałek, A; Kurach, Ł; Szpot, P; Zawadzki, M, 2021)	0.62
"A multimodal, opioid-free perioperative pain management pathway is safe and effective in patients undergoing total shoulder arthroplasty and offers superior pain relief to that of a traditional opioid-containing pain management pathway at 12 hours, 24 hours, and 2 weeks postoperatively."	( Opioid-free shoulder arthroplasty is safe, effective, and predictable compared with a traditional perioperative opiate regimen: a randomized controlled trial of a new clinical care pathway. Hamid, N; Jolissaint, JE; Leas, D; Odum, SM; Scarola, GT, 2022)	0.72
" The incidence of adverse effects was monitored."	( Analgesic Efficacy and Safety of Spinal Oxycodone in Total Hip Arthroplasty: A Preliminary Study. Adamski, M; Bienert, A; Kowalski, G; Leppert, W; Olczak, B; Szkutnik-Fiedler, D; Teżyk, A; Wieczorowska-Tobis, K, 2022)	0.72
" Regarding adverse effects, one patient had hypotension, one had bradycardia, and one had pruritus."	( Analgesic Efficacy and Safety of Spinal Oxycodone in Total Hip Arthroplasty: A Preliminary Study. Adamski, M; Bienert, A; Kowalski, G; Leppert, W; Olczak, B; Szkutnik-Fiedler, D; Teżyk, A; Wieczorowska-Tobis, K, 2022)	0.72
"Oxycodone in spinal block prolongs analgesia period, does not cause serious adverse effects and seems to be safe and effective opioid for patients undergoing THA."	( Analgesic Efficacy and Safety of Spinal Oxycodone in Total Hip Arthroplasty: A Preliminary Study. Adamski, M; Bienert, A; Kowalski, G; Leppert, W; Olczak, B; Szkutnik-Fiedler, D; Teżyk, A; Wieczorowska-Tobis, K, 2022)	0.72
" Adverse events were present in three RCTs (n=157), absent in 10 RCTs (n=957), and not reported in 25 RCTs (n=1570)."	( Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: a systematic review and meta-analysis of randomised trials. Belletti, A; Bollen Pinto, B; Putzu, A; Suter, M, 2022)	0.72
" Adverse events were rare but not systematically assessed."	( Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: a systematic review and meta-analysis of randomised trials. Belletti, A; Bollen Pinto, B; Putzu, A; Suter, M, 2022)	0.72
"Oliceridine, a new class of μ-opioid receptor agonist, may be associated with fewer opioid-related adverse events (ORAEs) due to its unique mechanism of action."	( Budget impact and pharmacy costs with targeted use of oliceridine for postsurgical pain in patients at high risk of opioid-related adverse events. Demitrack, MA; Fossler, MJ; Simpson, KN; Wandstrat, TL; Wase, L, 2022)	0.72
" The patients' charts were reviewed for the occurrence, timing, duration and management of adverse events, the vital signs at the night after surgery, and length of hospital stay."	( Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. de Graaff, JC; Houweling, BM; Koning, MV; Reussien, E; Vermeulen, BAN; Westerman, EM; Zonneveld, S, 2022)	0.97
"This study reveals that respiratory depression and somnolence are the predominant serious adverse events after intrathecal morphine in a perioperative setting and demonstrated a large variation in the presentation of symptoms."	( Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. de Graaff, JC; Houweling, BM; Koning, MV; Reussien, E; Vermeulen, BAN; Westerman, EM; Zonneveld, S, 2022)	1.17
"6 mg/kg has been shown to generate morphine and M6G concentrations comparable to that observed following administration of clinically effective doses of morphine, without the concomitant adverse effects observed with morphine administration."	( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses. Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022)	1
"The current study describes the metabolic profile and pharmacokinetics of codeine in horses and provides information that can be utilized in the design of future studies to understand the anti-nociceptive and analgesic effects of opioids in this species with the goal of promoting judicious and safe use of this important class of drugs."	( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses. Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022)	0.72
" We also found that norBNI treatment blocked the adverse effects of morphine on lesion size."	( Adverse Effects of Repeated, Intravenous Morphine on Recovery after Spinal Cord Injury in Young, Male Rats Are Blocked by a Kappa Opioid Receptor Antagonist. Araguz, K; Cunningham, R; Hemphill, A; Hook, MA; Rau, J; Stefanov, A; Weise, L, 2022)	1.22
" Adverse events were not observed in patients treated with ketamine."	( Efficacy and safety in ketamine-guided prehospital analgesia for abdominal pain. Dorau, W; Eppler, F; Häske, D; Heinemann, N; Schempf, B; Schopp, T, 2022)	0.72
" The primary endpoints are the effective rate of analgesia and the incidence of adverse reactions (nausea and vomiting, dizziness, itching, constipation, hypoxemia, and urinary retention); the secondary endpoints are pain intensity, satisfaction with analgesia, duration of surgery, postoperative hospital stay, average daily dose, uninterrupted completion rate of surgery without complaints of pain, quality of life assessment, and vital signs."	( Analgesic efficacy and safety of nalbuphine versus morphine for perioperative tumor ablation: a randomized, controlled, multicenter trial. Cheng, B; Huang, Z; Sun, J; Tang, Y; Wang, X; Xue, Y; Zhu, H, 2022)	0.97
" Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline."	( Intrathecal minocycline does not block the adverse effects of repeated, intravenous morphine administration on recovery of function after SCI. Brakel, K; Bryan, J; Cunningham, R; Hook, MA; Moore, R; Rau, J; Stefanov, A; Terminel, M; Weise, L, 2023)	1.36
"A survey questionnaire about the clinical experience with topical benzydamine and morphine to manage oral mucositis and their related adverse effects (AEs) was electronically distributed to the members of the Mucositis Study Group of MASCC/ISOO."	( Clinicians' experience with topical benzydamine and morphine for the management of oral mucositis: adverse effects and barriers. Blanchard, A; Bossi, P; Cheng, KKF; Elad, S; Levi, L; Yarom, N; Zadik, Y, 2022)	1.2
" By exploring the dose-response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects."	( Minimal important difference in opioid consumption based on adverse event reduction-A study protocol. Gasbjerg, KS; Geisler, A; Hägi-Pedersen, D; Jakobsen, JC; Karlsen, APH; Laigaard, J; Lunn, TH; Mathiesen, O; Pedersen, C; Thybo, KH, 2023)	0.91
" The primary outcome is the Hodges-Lehmann median difference in opioid consumption between patients with no opioid-related adverse effects and patients experiencing the mildest degree of one or more opioid-related adverse effects (i."	( Minimal important difference in opioid consumption based on adverse event reduction-A study protocol. Gasbjerg, KS; Geisler, A; Hägi-Pedersen, D; Jakobsen, JC; Karlsen, APH; Laigaard, J; Lunn, TH; Mathiesen, O; Pedersen, C; Thybo, KH, 2023)	0.91
" Secondary outcomes were intraoperative VAS scores assessed at multiple timepoints; intraoperative rescue analgesic requirement; postoperative VAS scores; disability scale; patients' satisfaction with anesthesia; adverse events; and radiographic outcomes."	( Effectiveness and safety of intrathecal morphine for percutaneous endoscopic lumbar discectomy under low-dose ropivacaine: a prospective, randomized, double-blind clinical trial. Lin, Z; Mu, G; Shang, M; Sun, H; Yue, L; Zhang, F, 2023)	1.18
" For adverse events, 8/43 of ITM and 1/44 of control participants experienced pruritus (p=."	( Effectiveness and safety of intrathecal morphine for percutaneous endoscopic lumbar discectomy under low-dose ropivacaine: a prospective, randomized, double-blind clinical trial. Lin, Z; Mu, G; Shang, M; Sun, H; Yue, L; Zhang, F, 2023)	1.18
" Patients requiring additional rescue analgesics or with adverse effects were documented."	( Efficacy and Safety of Low-Dose versus High-Dose Postoperative Intrathecal Morphine in 62 Women Undergoing Elective Cesarean Section Delivery at Full Term. Chen, Z; Fei, L; Jie, Y; Shuai, H; Zhefeng, Q, 2023)	1.14
" Our endpoints were the proportion of treatment responders to the oliceridine regimen and the incidence of adverse effects such as nausea and vomiting."	( Efficacy and safety of oliceridine treatment in patients with postoperative pain: a systematic review and meta-analysis of randomized controlled trials. Hu, W; Lu, Y; Niu, J; Tang, H, )	0.13
" Oliceridine was significantly associated with more adverse events such as nausea and vomiting compared to placebo."	( Efficacy and safety of oliceridine treatment in patients with postoperative pain: a systematic review and meta-analysis of randomized controlled trials. Hu, W; Lu, Y; Niu, J; Tang, H, )	0.13
"Our systematic review and meta-analysis showed that oliceridine is an effective and safe intravenous analgesic in patients with postoperative pain, producing rapid postoperative analgesic and usually well tolerated, and reducing incidence of adverse events compared to morphine."	( Efficacy and safety of oliceridine treatment in patients with postoperative pain: a systematic review and meta-analysis of randomized controlled trials. Hu, W; Lu, Y; Niu, J; Tang, H, )	0.31
" We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events."	( Comparative efficacy and safety of non-neuraxial analgesic techniques for midline laparotomy: a systematic review and frequentist network meta-analysis of randomised controlled trials. Bailey, JG; Barry, G; Retter, S; Sehmbi, H; Tablante, R; Uppal, V, 2023)	0.91

Pharmacokinetics

The increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations.Acute inhibition of P-glycoprotein by PSC in this setting does not affect the pharmacokinetics or safety-related pharmacodynamic profile of m.

Excerpt	Reference	Relevance
" Further, this analysis yielded 20 minutes as the half-life of naloxone."	( The relationship between pharmacokinetics and pharmacodynamic action as applied to in vivo pA2: application to the analgesic effect of morphine. Adler, MW; Geller, EB; Harakal, C; Maslow, J; Tallarida, RJ, 1978)	0.46
"The indications, contraindications and usefulness of pharmacodynamic tests in current radiological diagnosis of diseases of the digestive tract are reviewed and iscussed."	( [The employment of pharmacodynamic tests in the radiological examination of the digestive tract (author's transl)]. Basilico, L; Bonomo, L; Lupini, A; Renda, F, 1978)	0.26
" administration of morphine (1 or 5 mg/kg) the disappearance curves obtained with RIA-B were multiphasic and contained a prolonged terminal phase with an estimated half-life of 24 hours."	( Pharmacokinetics of morphine by radioimmunoassay: the influence of immunochemical factors. Catlin, DH, 1977)	0.91
"The use of pharmacological responses such as pupil diameter for dosage individualization, bioavailability, and pharmacokinetic analyses is becoming more widespread."	( Use of pharmacological data for bioavailability and pharmacokinetic analyses. Kramer, PA, 1977)	0.26
" Pharmacodynamic activity of salicylamide, morphine and hexobarbital were investigated."	( Influence of disorders of adrenal function of activity and pharmacokinetics of some neurotropic drugs. I. Influence of adrenalectomy on potency and pharmacokinetics of drugs. Cenajek, D, 1975)	0.52
" The assessment of the degree of tolerance to morphine and pharmacokinetic parameters were done 72 hr after pellet removal."	( Studies on the possible role of pharmacokinetics in the development of tolerance to morphine in the rat. Bhargava, HN; Larsen, AK; Rahmani, NH; Villar, VM, 1992)	0.77
" Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug."	( Evaluation of the accuracy of a pharmacokinetically-based patient-controlled analgesia system. Benedetti, C; Coda, B; Hill, H; Jacobson, R; Mackie, A; Schaffer, R, 1992)	0.51
" In order to determine if the differences in responses to morphine in SHR and WKY were related to its kinetics, the pharmacokinetic parameters of morphine in serum were determined."	( Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Bhargava, HN; Villar, VM, 1992)	0.76
" Half-life and volume of distribution were calculated using the postinfusion data."	( The maturation of morphine clearance and metabolism. Lynn, AM; McRorie, TI; Nespeca, MK; Opheim, KE; Slattery, JT, 1992)	0.62
" Blood and CSF samples were assayed for morphine and hydromorphone concentration to determine blood and CSF pharmacokinetic profiles."	( CSF and blood pharmacokinetics of hydromorphone and morphine following lumbar epidural administration. Brodsky, JB; Brose, WG; Cousins, MJ; Mark, JBD; Tanelian, DL, 1991)	0.8
" Such pharmacokinetic behavior appeared to be related to the contractive effect of morphine on the bile duct, and naloxone facilitated the excretion of morphine via this route."	( Naloxone affects both pharmacokinetics and pharmacodynamics of morphine. Application of direct correlation analysis. Ishikawa, K; Kogure, M; Kubo, T; Shibanoki, S, 1991)	0.75
" Canaliculi ligature modifies the morphine pharmacokinetic profile without significant modification of drug bioavailability."	( Systemic morphine pharmacokinetics after ocular administration. Bardin, C; Callaert, S; Chast, F; Chaumeil, JC; Sauvageon-Martre, H, 1991)	0.98
" The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound."	( Pharmacokinetics of intramuscular nicomorphine and its metabolites in man. Booij, LH; Dirksen, R; Koopman-Kimenai, PM; Nijhuis, GM; Vree, TB, 1991)	0.55
"Three case presentations illustrate clinically relevant pharmacokinetic properties of morphine."	( [Pharmacokinetic effects in morphine toxicity, with case examples]. Morant, R; Senn, HJ, 1991)	0.8
"Plasma hyoscine and morphine levels and various pharmacodynamic responses have been examined in seven patients scheduled for a coronary-artery bypass graft."	( Pharmacokinetics and clinical response of hyoscine plus morphine premedication in connection with cardiopulmonary bypass surgery. Arola, M; Kaila, T; Kanto, J; Kentala, E; Mattila, M, 1991)	0.85
"The pharmacokinetic profiles of two oral controlled-release morphine formulations, MS Contin tablets and Roxanol SR tablets, were compared to evaluate their bioequivalence."	( Comparison of the pharmacokinetic profiles of two oral controlled-release morphine formulations in healthy young adults. Hunt, TL; Kaiko, RF, )	0.6
"A single dose of activated charcoal (10 g) significantly reduced the half-life of elimination (1."	( Enhancement of morphine clearance following intravenous administration by oral activated charcoal in rabbits. el-Sayed, YM; Hasan, MM, 1990)	0.63
" Codeine exhibits characteristics consistent with a two-compartment pharmacokinetic model."	( A dose-ranging study of the pharmacokinetics of codeine phosphate following intravenous administration to rats. Mason, WD; Shah, J, 1991)	0.28
" Although morphine coadministration did not significantly affect the terminal half-life of naltrexone, its clearances or apparent volumes of distribution by t-test of the differences between averages (with each dog equally weighted), drug coadministration did significantly (by t-test) affect the fraction of naltrexone dose secreted into bile as conjugate (fB), the fraction of the dose excreted as conjugate in urine, and the fraction excreted elsewhere (f'B)."	( Pharmacokinetics of morphine and its surrogates. XI: Effect of simultaneously administered naltrexone and morphine on the pharmacokinetics and pharmacodynamics of each in the dog. Garrett, ER; Khan, PJ; Langguth, P, 1990)	1.01
" The method employs a computer-controlled infusion pump and an algorithm that utilizes individual subject pharmacokinetic parameters predetermined with tailoring bolus opioid doses."	( Steady-state infusions of opioids in human volunteers. I. Pharmacokinetic tailoring. Bjurstrom, R; Chapman, CR; Donaldson, G; Hill, HF; Jacobson, R; Saeger, L, 1990)	0.28
" This terminal rate constant was in contrast to the less than 100 min half-life of the second exponential fitting of the less lipophilic morphine, naloxone, and naltrexone."	( Pharmacokinetics of morphine and its surrogates. X: Analyses and pharmacokinetics of buprenorphine in dogs. Chandran, VR; Garrett, ER, )	0.66
" Values of elimination half-life ranged from 13."	( Pharmacokinetics of propofol when given by intravenous infusion. Campbell, GA; Crankshaw, DP; Morgan, DJ, 1990)	0.28
" Pharmacokinetic profiles of morphine base were measured over a 24-h period using 13 sampling times."	( Age and the pharmacokinetics of morphine. Baillie, SP; Bateman, DN; Coates, PE; Woodhouse, KW, 1989)	0.85
"The clinical pharmacology and pharmacodynamic data from several clinical trials are summarized."	( Clinical pharmacology, pharmacodynamics and interactions with esmolol. Bies, CM; Lowenthal, DT; Porter, RS; Saris, SD; Slegowski, MB; Staudacher, A, 1985)	0.27
" The terminal plasma half-life averaged 91 +/- 34 min and 87 +/- 27 min, respectively (mean +/- SEM)."	( Pharmacokinetics of epidural morphine and meperidine in humans. Hartvig, P; Persson, MP; Sjöström, S; Tamsen, A, 1987)	0.56
" After a rapid initial decline for about 15 min after injection, the CSF concentrations decreased with a half-life of 89."	( Pharmacokinetics of intrathecal morphine and meperidine in humans. Hartvig, P; Persson, MP; Sjöström, S; Tamsen, A, 1987)	0.56
" The administration procedure was based on the pharmacokinetic parameters of CMI determined in the strain used."	( Pharmacokinetic patterns of repeated administration of antidepressants in animals. II. Their relevance in a study of the influence of clomipramine on morphine analgesia in mice. Civiale, MA; Eschalier, A; Fialip, J; Makambila, MC; Marty, H, 1989)	0.48
" Pharmacokinetic parameters were similar to those observed after epidural injection of morphine in adults, except for a shorter terminal half-life (73."	( Epidural morphine in children: pharmacokinetics and CO2 sensitivity. Attia, J; Ecoffey, C; Gross, JB; Samii, K; Sandouk, P, 1986)	0.91
" Codeine elimination half-life and mean residence time were increased significantly in the hemodialysis group (18."	( Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1988)	0.27
" The moments of the morphine concentration-time curves and the pharmacokinetic parameters varied between the patients."	( The pharmacokinetics of intradural morphine in major abdominal surgery. Drost, RH; Ionescu, TI; Roelofs, JM; Taverne, RH; van Maris, AA; van Rossum, JM; Winckers, EK, 1988)	0.88
" After the intravenous administration of 10 mg/kg morphine, the plasma half-life of morphine was significantly prolonged by adrenalectomy without any effect on the volume of morphine distribution."	( Effects of adrenalectomy on pharmacokinetics and antinociceptive activity of morphine in rats. Miyamoto, Y; Ozaki, M; Yamamoto, H, 1988)	0.76
" The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups."	( Pharmacokinetics of different epidural sites of morphine administration. Hansdottir, V; Hedner, T; Kvist, L; Mellstrand, T; Nordberg, G, 1987)	0.95
" Peak concentration and AUC24 data for morphine glucuronide indicated that significant accumulation of this compound occurs upon multiple-dose administration."	( Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers. Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1987)	0.54
" Recent pharmacokinetic studies have confirmed the rationale for regular administration of oral morphine and methadone but have revealed marked interindividual differences in the kinetics and metabolism which must be considered when titrating the oral dose according to the individual patient's need."	( High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Säwe, J, )	0.75
" The long half-life of methadone was associated with prolonged pain relief."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.5
" The simultaneous administration of naloxone does not reverse the dose-dependent pharmacokinetic perturbations of morphine."	( Pharmacokinetics of morphine and its surrogates. VIII: Naloxone and naloxone conjugate pharmacokinetics in dogs as a function of dose and as affected by simultaneously administered morphine. Garrett, ER; Shyu, WC; Ulubelen, A, 1986)	0.8
" In the present study, the pharmacokinetic characteristics of morphine were studied in five subjects receiving a constant rate intravenous infusion with the attainment of a steady state."	( [Prolonged intravenous infusion of morphine. Pharmacokinetic study]. Gibassier, D; Le Verge, R; Malledant, Y; Saint-Marc, C; Tanguy, M, 1987)	0.79
" The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS."	( Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. Evans, W; Khojasteh, A; Reynolds, RD; Savarese, JJ; Thomas, G, 1987)	0.58
" A physiologically based pharmacokinetic model was used to describe the disposition of morphine in post-operative patients."	( Potential pulmonary uptake and clearance of morphine in postoperative patients. Hartvig, P; Paalzow, L; Persson, MP; Wiklund, L, 1986)	0.76
"1 mg/kg was described by a bi- or triexponential decay equation with a mean terminal half-life (t1/2) of 134."	( Pharmacokinetics of morphine after epidural administration in man. Drost, RH; Ionescu, TI; Maes, RA; van Rossum, JM, 1986)	0.59
" In the shocked patients the elimination half-life of morphine was significantly prolonged (13."	( Profound reduction in morphine clearance and liver blood flow in shock. Feely, J; Grant, IS; Guy, E; Macnab, MS; Macrae, DJ, 1986)	0.83
" Time to maximum concentration was 3 times longer for controlled release tablets with an absorption half-life twice that of the solution."	( Steady-state pharmacokinetics of controlled release oral morphine sulphate in healthy subjects. Goldenheim, PD; Kaiko, RF; Savarese, JJ; Thomas, GB, )	0.38
" The combination of lower clearance and longer elimination half-life in newborns (0-7 days) may well explain a prolonged duration of action for morphine in very young infants, but other etiologies are needed to explain the respiratory sensitivity believed to persist in older infants."	( Morphine pharmacokinetics in early infancy. Lynn, AM; Slattery, JT, 1987)	1.92
" The pharmacodynamic consequences of these dosage characteristics are the rapid development of tolerance and maintenance of physical dependence during the period of the implant."	( Pharmacokinetics and pharmacodynamics of subcutaneous morphine pellets in the rat. Chen, J; Huang, T; Inturrisi, CE; Yoburn, BC, 1985)	0.52
" The intravenous administration of 2 resulted in two sequential half-lives of 3 and 270 min and no apparent pharmacokinetic dose dependency."	( Pharmacokinetics of morphine and its surrogates. VII: High-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. Derendorf, H; Garrett, ER; Mattha, AG, 1985)	0.59
"We have studied the distribution of antidepressant agents, morphine and apomorphine, in rat blood and tissues and correlated the pharmacokinetic data with pharmacological responses induced by these drugs."	( Pharmacokinetic aspects of some behavioral effects of psychotropic drugs. Melzacka, M, )	0.37
"This paper has attempted to review some of the possibilities we have today to describe the relationships between the kinetics of a drug and the pharmacodynamic responses."	( Integrated pharmacokinetic-dynamic modeling of drugs acting on the CNS. Paalzow, LK, 1984)	0.27
" The results indicate that the analgesic effect of morphine in the tail-flick test is correlated better with the spinal than cerebral morphine levels and that potentiation of morphine analgesia by haloperidol is due, at least in part, to pharmacokinetic interaction."	( Behavioral and pharmacokinetic interaction between morphine and haloperidol in the rat. Adamus, A; Melzacka, M; Vetulani, J, )	0.64
" Results obtained for pharmacokinetic parameters after intravenous administration in man are in agreement with published data using GLC or HPLC."	( Sensitive and specific morphine radioimmunoassay with iodine label: pharmacokinetics of morphine in man after intravenous administration. Allen, MC; Baldwin, D; Bullingham, RE; McQuay, HJ; Moore, RA; Watson, PJ, 1984)	0.58
"50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study."	( Pharmacokinetic aspects of intrathecal morphine analgesia. Dahlström, B; Hedner, T; Mellstrand, T; Nordberg, G, 1984)	1.02
" The comparison of serum morphine levels in patients who reported a very short lasting and very long lasting analgesia gave us no pharmacokinetic explanation for this difference."	( [Peridural morphine analgesia: effects and pharmacokinetics. A double-blind study in vaginal hysterectomy patients]. Dick, W; Harzenetter, J; Kossmann, B; Möller, MR; Traub, E; Wollinsky, KH, 1983)	0.96
" There were no significant differences in the biological half-life (T1/2), the apparent volume of distribution (Vd), and the clearance (C) of antipyrine and paracetamol."	( Pharmacokinetics of antipyrine, paracetamol, and morphine in rat at 71 ATA. Aanderud, L; Bakke, OM, 1983)	0.52
" Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated."	( Pharmacokinetics of epidural morphine in man. Borg, L; Hedner, T; Mellstrand, T; Nordberg, G, 1984)	0.94
" The decay of plasma concentration fitted a three-compartment mamillary pharmacokinetic model in all subjects."	( Pharmacokinetics of single-dose i.v. morphine in normal volunteers and patients with end-stage renal failure. Achola, K; Aitkenhead, AR; Cooper, CM; Smith, G; Vater, M, 1984)	0.54
" The plasma curves had a similar appearance as after an intramuscular injection and pharmacokinetic calculations showed an elimination half-life (mean +/- SEM) of 173 +/- 24 min, 200 +/- 60 min, and 213 +/- 57 min for the groups, respectively."	( Pharmacokinetic aspects of epidural morphine analgesia. Dahlström, B; Hedner, T; Mellstrand, T; Nordberg, G, 1983)	0.54
" An increase in the partition of morphine into the maternal muscle produced an increase in the terminal half-life in all tissues including the foetus."	( A physiological pharmacokinetic model for morphine disposition in the pregnant rat. Gabrielsson, JL; Paalzow, LK, 1983)	0.81
" groups showed the same pharmacokinetic patterns although extradural analgesia is much more prolonged."	( Plasma pharmacokinetics of morphine after i.m., extradural and intrathecal administration. Bourdon, R; Chauvin, M; Samii, K; Sandouk, P; Schermann, JM; Viars, P, 1982)	0.56
"The number of scientific papers dealing with pharmacokinetic investigations has grown almost exponentially during recent years."	( Pharmacokinetic aspects of optimal pain treatment. Paalzow, LK, 1982)	0.26
" This overestimation did not significantly affect the values for terminal elimination half-life, volume of distribution at steady state, or total body clearance that were derived using results from each assay and model-independent pharmacokinetic techniques."	( Morphine pharmacokinetics: GLC assay versus radioimmunoassay. Edlund, PO; Paalzow, L; Stanski, DR, 1982)	1.71
" These pharmacodynamic studies, along with prior dispositional studies, suggest that the ability of DAM and AM to rapidly cross the blood-brain barrier determines their potency and time-action differences from M in centrally mediated bioassays."	( Pharmacodynamics of subcutaneously administered diacetylmorphine, 6-acetylmorphine and morphine in mice. Inturrisi, CE; Umans, JG, 1981)	0.51
" Nevertheless, the terminal half-life of 60-90 min resembles that of morphine and is maintained by the rate-determining return of distributed heroin from esterase-free tissues."	( Pharmacokinetics of morphine and its surrogates IV: Pharmacokinetics of heroin and its derived metabolites in dogs. Garrett, ER; Gürkan, T, 1980)	0.82
" Morphine 5 mg was given intravenously and serial blood and urine samples were drawn to derive pharmacokinetic parameters."	( Acute trauma alters morphine clearance. Christie, J; Markowsky, SJ; Valdes, C, 1995)	1.52
" In BECF, the Tmax value for M6G was lower than for morphine, but the t1/2 beta values did not differ."	( Analgesic response and plasma and brain extracellular fluid pharmacokinetics of morphine and morphine-6-beta-D-glucuronide in the rat. Barjavel, MJ; Bhargava, HN; Plotkine, M; Sandouk, P; Scherrmann, JM; Stain, F, 1995)	0.77
"A pharmacodynamic interactional study with omeprazole was undertaken in rats."	( Pharmacodynamic interactions of omeprazole with CNS active drugs in rats. Chakrabarti, A; Chandrashekhar, SM; Garg, SK, 1995)	0.29
" Pharmacokinetic analysis of the results revealed that MS was eliminated by a first-order process best described by a two-compartment model."	( Pharmacokinetics of parenteral and oral sustained-release morphine sulphate in dogs. Dohoo, S; Donald, A; Tasker, RA, 1994)	0.53
" In four patients, full 12-hr plasma morphine concentration profiles at steady state were obtained and showed no significant differences between the same dose provided as 100-mg and 200-mg tablets in Cmax, tmax, or other pharmacokinetic indices."	( Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg tablet. Finlay, I; Hanks, GW; Hanna, M; Keeble, T; Radstone, DJ, 1995)	0.81
"61) ml/kg/min and terminal half-life (T1/2) was 224 (107-394) min."	( Morphine pharmacokinetics in premature and mature newborn infants. Christensen, CB; Feilberg, VL; Lundstrøm, KE; Mikkelsen, S, 1994)	1.73
" The apparent terminal half-life for MS-OS was 3 hours, which is similar to that of patients without burns, but the apparent terminal half-life for the MS-CR in patients with burns was substantially longer at 14."	( Pharmacokinetics of morphine sulfate in patients with burns. Herman, RA; Kealey, GP; Komorowski, J; Miotto, J; Veng-Pedersen, P, )	0.45
" Pharmacokinetic values were calculated using noncompartmental analysis."	( A two-dose epidural morphine regimen in cesarean section patients: pharmacokinetic profile. Ramanathan, S; Turndorf, H; Zakowski, MI, 1993)	0.61
" Pharmacokinetic analyses failed to suggest an advantage of sublingual administration when compared with oral dosing."	( Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. Ames, MM; Burnham, NL; Davis, T; Dose, AM; Kaur, JS; Loprinzi, CL; Miser, AW, 1993)	0.66
"89 l kg-1, the half-life of the first phase 13."	( Pharmacokinetics and pharmacodynamics of morphine-3-glucuronide in rats and its influence on the antinociceptive effect of morphine. Ekblom, M; Gårdmark, M; Hammarlund-Udenaes, M, 1993)	0.55
"5 mg/kg) on the pharmacokinetic parameters area under the serum morphine concentration time curve (AUC0-->infinity), serum levels of morphine extrapolated to zero time (Cmax), half-life (t1/2), mean residence time (MRT), total body clearance (Clt), and volume of distribution at steady state (Vss) of morphine in serum was determined."	( Effects of naltrexone on pharmacodynamics and pharmacokinetics of intravenously administered morphine in the rat. Bhargava, HN; Larsen, AK; Rahmani, NH; Villar, VM, 1993)	0.74
" The terminal half-life of normorphine was 23."	( Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Hasselström, J; Säwe, J, 1993)	2.02
" For each drug, an effect compartment pharmacodynamic model was fit to the values for minute ventilation to determine the steady-state opioid plasma concentration depressing ventilation by 50% (C50) and the rate constant for equilibration between plasma concentration and effect (keo)."	( Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl. Bragg, P; Fisher, DM; Lau, M; Zwass, MS, 1995)	0.53
"The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or after a high-fat breakfast."	( Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus. Aliyar, CA; Crawford, FE; Drake, J; Gibson, P; Horth, CE; Kirkpatrick, CT, 1996)	0.53
" Mean values of Cmax were 76 nmol/l (25-129) and 56 nmol/1 (15-140), respectively."	( Rectal administration of morphine in children. Pharmacokinetic evaluation after a single-dose. Beck, O; Boreus, LO; Lundeberg, S; Olsson, GL, 1996)	0.6
"The rectal morphine hydrogel has pharmacokinetic properties which makes it a useful formulation for premedication and pain alleviation in paediatric patients."	( Rectal administration of morphine in children. Pharmacokinetic evaluation after a single-dose. Beck, O; Boreus, LO; Lundeberg, S; Olsson, GL, 1996)	0.99
"60 ml min-1 kg-1, the elimination half-life was 11."	( Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions. Barker, DP; Barrett, DA; Pawula, M; Rutter, N; Shaw, PN, 1996)	1.74
" This dosing regimen may be used in further pharmacodynamic studies to compare the analgesic effects of morphine and M-6-G."	( Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers. Brune, K; Geisslinger, G; Kobal, G; Lötsch, J; Schmidt, N; Stockmann, A; Waibel, R, 1996)	0.83
"A pharmacokinetic study was undertaken to compare the pharmacokinetics of morphine after an intravenous dose with the pharmacokinetics after a sublingual dose administered from an aerosol."	( A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers. Eden, OB; Joel, SP; Slevin, ML; Taylor, KM; Watson, NW, 1996)	0.78
"kg-1, seems to be regardless of age, while half-life and clearance were found to be related to age."	( Recommended use of morphine in neonates, infants and children based on a literature review: Part 1--Pharmacokinetics. Christrup, LL; Kart, T; Rasmussen, M, 1997)	0.63
" Patients were admitted to the Pain Management Unit on the morning of day 7 (+/- 1 day) and frequent blood samples were collected for 24 h following the 10:00 h dose to fully characterise the pharmacokinetic profile for morphine and its metabolites at steady state."	( Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain. Cherry, DA; Conn, DA; Gourlay, GK; Hood, GM; Onley, MM; Plummer, JL; Tordoff, SG, 1997)	0.48
" Pharmacokinetic analysis revealed that there were no significant differences between trough serum concentrations for the concentration-time curves within either treatment group, indicating that steady-state pharmacokinetics had been achieved."	( Steady-state pharmacokinetics of oral sustained-release morphine sulphate in dogs. Dohoo, S, 1997)	0.54
" Plasma samples were masked for pharmacokinetic analysis."	( The effect of food intake on the pharmacokinetics of sustained-release morphine sulfate capsules. Kaiko, RF, )	0.36
" The method is suitable for pharmacokinetic studies after subclinical doses of morphine where it has been used to study morphine plasma concentrations for 6 h after a dose of only 2 mg."	( Highly sensitive gas chromatographic-mass spectrometric method for morphine determination in plasma that is suitable for pharmacokinetic studies. Dawson, M; Fryirs, B; Mather, LE, 1997)	0.76
" Pharmacokinetic parameters for both oral formulations exhibited large variability in the rate of absorption of MS from the gastrointestinal tract."	( Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations. Dohoo, SE; Tasker, RA, 1997)	0.6
" Pharmacokinetic analysis revealed that morphine release from the gel matrix was significantly prolonged but fully bioavailable."	( Pharmacokinetics of an injectable sustained-release formulation of morphine for use in dogs. Dohoo, SE; Elson, CM; Ross, SJ; Tasker, RA, 1997)	0.8
" There was no correlation between the time to peak analgesia and time to peak concentration for morphine or M-6-G."	( A pharmacodynamic study of morphine and its glucuronide metabolites after single morphine dosing in cancer patients with pain. Citron, M; Degaetano, C; Fanelli, C; Hoffman, M; Lehrer, M; Lesser, M; Meenan, G; Pascal, V; Smith, C; Xu, JC, 1997)	0.81
"8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively."	( Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system. Farr, SJ; Lloyd, P; Mather, LE; Okikawa, JK; Rubsamen, RM; Schuster, JA; Ward, ME; Woodhouse, A, 1997)	1.74
" An effect compartment pharmacodynamic model was fit to the values for time to response to determine the rate constant for equilibration (Keo) between plasma and effect-site (Ce) concentrations and analgesic effect (increase in time to response to a noxious stimulus) above baseline per microgram/ml of Ce (delta)."	( Opioid-induced analgesia in neonatal dogs: pharmacodynamic differences between morphine and fentanyl. Brown, RC; Chari, G; Fisher, DM; Lau, M; Luks, AM; Zwass, MS, 1998)	0.53
" The pharmacokinetic parameters half-life, terminal elimination rate constant and the mean residence time were determined in both cerebrospinal fluid and plasma by non-compartmental analysis."	( Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and sensitized rats. Bhargava, HN; Cortijo, J; Morcillo, EJ; Villar, VM, 1998)	0.51
" The present assay was applied to a pharmacokinetic study in rats after intraperitoneal administration of morphine."	( High-performance liquid chromatography-mass spectrometry-mass spectrometry analysis of morphine and morphine metabolites and its application to a pharmacokinetic study in male Sprague-Dawley rats. McErlane, KM; Ong, MC; Zheng, M, 1998)	0.74
" A loading dose based on the Vd at the tmax will accurately achieve the concentration at the tmax without unexpected adverse effects."	( Determination of the distribution volume that can be used to calculate the intravenous loading dose. Drover, DR; Lemmens, HJ; Wada, DR, 1998)	0.3
" Following single doses, the plasma morphine concentrations showed pronounced differences in the 0- to 12-hour period with a 4- to 5-fold difference in the mean peak concentration (Cmax) for morphine and the time to Cmax (tmax) The area under the concentration-time curve (AUC) from 0 to 24 hours for the 4 formulations show greater similarity."	( Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine. Gourlay, GK, 1998)	0.81
" Our data suggest that the increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations."	( The influence of hemorrhagic shock on the pharmacokinetics and the analgesic effect of morphine in the rat. Belpaire, FM; Buylaert, WA; De Paepe, P; Rosseel, MT, 1998)	0.77
" The estimates of pharmacokinetic parameters based on unbound plasma concentrations did not differ between groups, with the sole exception of the unbound apparent volume of distribution."	( Altered plasma and brain disposition and pharmacodynamics of methadone in abstinent rats. Calvo, R; Garrido, MJ; Trocóniz, IF; Valle, M, 1999)	0.3
" For immediate-release morphine there was no difference in either dose-corrected Cmax or Tmax between solution and tablets, or between different salts."	( Peak plasma concentrations after oral morphine: a systematic review. Collins, SL; Faura, CC; McQuay, HJ; Moore, RA, 1998)	0.88
"When trovafloxacin was coadministered with morphine, the half-life of trovafloxacin was unchanged; however, the ratio of the area under the serum concentration versus time curve (AUC(0-infinity)) estimates for trovafloxacin/morphine versus trovafloxacin/placebo was 63."	( The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects. Friedman, HL; Hunt, T; Robarge, L; Teng, R; Vincent, J; Willavize, SA, 1998)	0.81
"To evaluate the pharmacokinetic parameters of morphine and lidocaine after a single intravenous dose in critically ill patients."	( The pharmacokinetics of morphine and lidocaine in critically ill patients. Almog, S; Berkenstadt, H; Ezra, D; Mayan, H; Perel, A; Rotenberg, M; Segal, E, 1999)	0.87
" No correlation was found between clinical variables and pharmacokinetic parameters of both drugs (ANOVA)."	( The pharmacokinetics of morphine and lidocaine in critically ill patients. Almog, S; Berkenstadt, H; Ezra, D; Mayan, H; Perel, A; Rotenberg, M; Segal, E, 1999)	0.61
" The peak concentration (Cmax, %ID/g) and time corresponding to the peak (tmax, h) were obtained."	( Fetal distress does not affect in utero defecation but does impair the clearance of amniotic fluid. Bingöl-Koloğlu, M; Büyükpamukçu, N; Ciftci, AO; Sahin, S; Tanyel, FC, 1999)	0.3
" (3) In liver and bowel, shape of the profile was bimodal because of fetal swallowing and similar in both groups, tmax was the same in both groups, Cmax was lower in group B than in group A, the total uptake was smaller in group B than in group A, and intestinal transport time was similar (44."	( Fetal distress does not affect in utero defecation but does impair the clearance of amniotic fluid. Bingöl-Koloğlu, M; Büyükpamukçu, N; Ciftci, AO; Sahin, S; Tanyel, FC, 1999)	0.3
" The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine."	( Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Ahne, G; Geisslinger, G; Kobal, G; Lötsch, J; Weiss, M, 1999)	0.85
" Plasma pharmacokinetic parameters for racemic drug and both enantiomers were determined for each patient."	( Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Aravind, MK; Kauffman, RE; Lieh-Lai, MW; Uy, HG, 1999)	0.3
" Terminal half-life of S(-)-ketorolac was 40% that of the R(+) enantiomer, and the apparent volume of distribution of the S(-) enantiomer was greater than that of the R(+) form."	( Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Aravind, MK; Kauffman, RE; Lieh-Lai, MW; Uy, HG, 1999)	0.3
" Because of the greater clearance and shorter half-life of S(-)-ketorolac, pharmacokinetic predictions based on racemic assays may overestimate the duration of pharmacologic effect."	( Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Aravind, MK; Kauffman, RE; Lieh-Lai, MW; Uy, HG, 1999)	0.3
"This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years)."	( Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis. Hofmann, U; Kuhlmann, U; Mettang, T; Mikus, G; Pauli-Magnus, C, 1999)	0.63
" Population pharmacokinetic parameters were derived with the program P-PHARM."	( Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. Dick, G; Goldman, A; Hunt, A; Joel, S, 1999)	0.58
"In order to evaluate pharmacokinetic interactions between heroin and alcohol and their role in the etiology of heroin-related deaths (HRD), the alcohol concentration in blood (BAC), the free (FM) and total morphine (TM) concentrations in blood (determined by DPC Coat-A-Count radioimmunoassay before and after enzymatic hydrolysis), and the TM concentration in urine and bile (DPC Coat-A-Count after enzymatic hydrolysis) in a population of 39 lethal cases included in the records of the Department of Legal Medicine and Public Health at the University of Pavia from the period January 1997-April 1998 were examined."	( The role of alcohol abuse in the etiology of heroin-related deaths. Evidence for pharmacokinetic interactions between heroin and alcohol. Groppi, A; Montagna, M; Polettini, A, )	0.32
"To study the pharmacokinetic parameters of morphine and lidocaine after a single intravenous (i."	( The pharmacokinetics of morphine and lidocaine in nine severe trauma patients. Almog, S; Berkenstadt, H; Ezra, D; Mayan, H; Perel, A; Rotenberg, M; Segal, E, 1999)	0.87
" The enhancement of MS analgesia by DM is due to a pharmacodynamic interaction, not an effect on MS blood levels or a pharmacokinetic interaction between MS and DM, or their metabolites."	( MorphiDex pharmacokinetic studies and single-dose analgesic efficacy studies in patients with postoperative pain. Caruso, FS, 2000)	0.31
" morphine, the concentrations of morphine, M6G and M3G and their pharmacokinetic parameters were similar to those we have observed previously, in other healthy volunteers (when standardized to nmol l- 1, for a 10 mg dose to a 70 kg subject)."	( The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine. Currow, D; Joel, SP; McDonald, P; Slevin, ML; Stuart-Harris, R, 2000)	1.52
" Using SAAM II pharmacokinetic modeling software (SAAM Institute, University of Washington, Seattle, WA), the data were fit to a 16-compartment model that was divided into four spinal levels, each of which consisted of a caternary arrangement of four compartments representing the spinal cord, cerebrospinal fluid, epidural space, and epidural fat."	( Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Arends, RH; Bernards, CM; Shen, DD; Ummenhofer, WC, 2000)	0.53
"The four opioids studied demonstrate markedly different pharmacokinetic behavior, which correlates well with their pharmacodynamic behavior."	( Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Arends, RH; Bernards, CM; Shen, DD; Ummenhofer, WC, 2000)	0.53
"The pharmacokinetic profiles, safety, and tolerability of continuous subcutaneous infusion with a novel drug deliver system (the MEDIPAD system) was compared to a standard infusion pump (the CADD-Micro) and to controlled-release tablets (MS Contin) for the administration of morphine sulfate."	( A pharmacokinetic and tolerability evaluation of two continuous subcutaneous infusion systems compared to an oral controlled-release morphine. Butler, J; Davidson, D; Hamm, S; Huerta, D; Mikkelsen Lynch, P; Tsals, I, 2000)	0.69
" Blood for determination of plasma concentration of morphine (M) and its 3- and 6-glucuronides (M3G, M6G) was collected, and area under the plasma concentration-time curve (AUC)0-12 h, peak plasma concentration (Cmax), time to reach Cmax (tmax), and CO and C12 of M, M6G and M3G were determined on day 5 and day 10."	( Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain. Frijlink, HW; Meijler, WJ; Moolenaar, F; Proost, JH; Visser, J, 2000)	0.78
" Apart from the C0 and C12, no significant differences in AUC0-12 h, tmax and Cmax of morphine between the rectal and oral route of administration were found."	( Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain. Frijlink, HW; Meijler, WJ; Moolenaar, F; Proost, JH; Visser, J, 2000)	0.75
" Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models."	( Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Connors, PM; Dershwitz, M; Morishige, RJ; Rosow, CE; Rubsamen, RM; Shafer, SL; Walsh, JL, 2000)	0.54
"The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time."	( Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Connors, PM; Dershwitz, M; Morishige, RJ; Rosow, CE; Rubsamen, RM; Shafer, SL; Walsh, JL, 2000)	0.54
"To investigate the effect of acute P-glycoprotein inhibition by the multidrug-resistance (MDR) modulator valspodar (SDZ PSC 833; PSC) on the pharmacokinetics, and potentially adverse pharmacodynamic effects of morphine, and its principal pharmacologically active metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.71
"In a double-blind, three-way crossover study, the pharmacokinetic and potentially adverse pharmacodynamic effects (reaction time, transcutaneous PCO2, blood pressure) of morphine were compared with and without acute inhibition of P-glycoprotein by PSC."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.72
" were unaffected there was a small but statistically significant increase in the AUC and Cmax of M3G (11."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.53
"Acute inhibition of P-glycoprotein by PSC in this setting does not affect the pharmacokinetic or safety-related pharmacodynamic profile of morphine in a clinically significant manner."	( Effect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine. Ball, HA; Beglinger, C; Drewe, J; Haefeli, WE; Kemmler, A; Peng, B; Schächinger, H, 2000)	0.73
" The pharmacokinetic profiles of M and inactive morphine-3-glucuronide (M3G) in morphine-treated mice nearly overlapped those in heroin-treated mice, with the only difference being the presence of 6-monoacetylmorphine (AM) in profiles of the latter group."	( Pharmacokinetics and cytokine production in heroin and morphine-treated mice. Bacosi, A; di Carlo, S; Pacifici, R; Pichini, S; Zuccaro, P, 2000)	0.81
"This article outlines the main pharmacokinetic and toxicokinetic parameters of selected addicting compounds often being abused."	( [Pharmacokinetic and toxicokinetic parameters of some drugs of abuse]. Panas, M, 2001)	0.31
" Pharmacokinetic (PK) parameters were calculated and bioequivalence assessed."	( Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation. Butler, J; Devane, J; Eliot, L; Loewen, G, 2002)	0.54
" Cmax and total systemic exposure-based on AUC from time 0 to the last quantifiable concentration (AUC(last)) and AUC from time 0 to infinity (AUC(infinity))-were comparable between treatments."	( Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation. Butler, J; Devane, J; Eliot, L; Loewen, G, 2002)	0.54
" The primary objective of this study was to compare the 24-hour steady-state pharmacokinetic (PK) profiles of morphine and its metabolites (morphine-6-glucuronide [M6G] and morphine-3-glucuronide [M3G]) following ingestion of MSER once-a-day and MS Contin (controlled-release morphine sulfate [CRM]) twice-a-day in patients with chronic moderate-to-severe pain."	( Steady-state pharmacokinetic comparison of a new, extended-release, once-daily morphine formulation, Avinza, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain. Butler, J; Devane, J; Eliot, L; Loewen, G; Portenoy, RK; Sciberras, A, 2002)	0.75
" The present study aimed to explore pharmacokinetic differences between morphine and morphine-glucuronides in mice after different routes of administration, and to investigate how possible differences were reflected in locomotor activity, a measure of psychostimulant properties."	( Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity. Grung, M; Handal, M; Mørland, J; Ripel, A; Skurtveit, S, 2002)	0.83
" Concentration time-course and interindividual variability of morphine (M), morphine-3-glucuronide (M3G) and morphine-6 glucuronide (M6G) were analysed using population pharmacokinetic modelling."	( Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine. Brockmöller, J; Freudenthaler, S; Gleiter, CH; Hofmann, U; Meineke, I; Mikus, G; Prange, HW; Schaeffeler, E; Schwab, M, 2002)	0.85
"From the population pharmacokinetic model presented, CSF concentration profiles can be derived for M, M3G and M6G on the basis of dosing information and creatinine clearance without collecting CSF samples."	( Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine. Brockmöller, J; Freudenthaler, S; Gleiter, CH; Hofmann, U; Meineke, I; Mikus, G; Prange, HW; Schaeffeler, E; Schwab, M, 2002)	0.61
" The pharmacokinetic profile of intranasal diamorphine in adults has been systematically studied."	( Intranasal diamorphine as an alternative to intramuscular morphine: pharmacokinetic and pharmacodynamic aspects. Kendall, JM; Latter, VS, 2003)	0.94
" The data were analyzed using a population dose-driven approach, which uses a dose rate in function of time as input function driving the pharmacodynamics, and a population pharmacokinetic-pharmacodynamic (PK/PD) approach in which fixed pharmacokinetic parameter values from the literature were used as input function to the respiratory model."	( Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers. Dahan, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L, 2003)	0.62
" Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events."	( Clinical pharmacokinetics of morphine. Kern, SE; Lugo, RA, 2002)	0.82
" A population pharmacokinetic (inhibitory sigmoid Emax)-pharmacodynamic analysis was used to analyze M6G-induced changes in tolerated stimulus intensity."	( Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences. Dahan, A; den Hartigh, J; Olofsen, E; Romberg, R; Sarton, E; Taschner, PE, 2004)	0.58
" The volume of distribution increased exponentially with a maturation half-life of 26 days from 83 litres per 70 kg at birth; formation clearance to M3G and M6G increased with a maturation half-life of 88."	( Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Anderson, BJ; Bouwmeester, NJ; Holford, NH; Tibboel, D, 2004)	0.6
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."	( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004)	0.32
"The present study was designed to investigate the pharmacokinetic interaction of morphine with three classes of L-type calcium channel blockers (CCB) and its relationship to morphine-induced mechanical antinociception in mice."	( Role of pharmacokinetic effects in the potentiation of morphine analgesia by L-type calcium channel blockers in mice. Fukazawa, Y; Kishioka, S; Maeda, T; Ozaki, M; Shimizu, N; Yamamoto, C; Yamamoto, H, 2004)	0.8
"Mean tmax values were similar following all dose groups at approximately 1-2 minutes."	( Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma. Linn, L; Morishige, R; Okikawa, J; Otulana, B; Thipphawong, J, 2004)	0.59
" Pharmacodynamic modeling suggested that this latter effect was consistent with a hyperalgesic response."	( Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Heinzen, EL; Pollack, GM, 2004)	0.65
"We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls."	( Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma. El-Kabsh, MY; El-Kady, SA; Emara, SE; Fouad, EA; Kotb, HI, 2005)	0.6
"5 l per hour per 70 kg) but increased rapidly (maturation half-life 30 and 70 days, respectively) and equaled that of the postoperative group after 14 days."	( Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Anderson, BJ; Peters, JW; Simons, SH; Tibboel, D; Uges, DR, 2005)	1.77
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 2005)	0.33
" Large patient-to-patient variations in pharmacokinetic parameters occurred, although intraindividual variability was limited."	( Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients. Bressolle, F; Caumette, L; Culine, S; Garcia, F; Pinguet, F; Poujol, S; Solassol, I, 2005)	0.33
"In order to perform a reliable pharmacokinetic study of morphine during subchronic treatment in rats, an easy, rapid, sensitive and selective analytical method was proposed and validated."	( High-performance liquid chromatographic assay for morphine in small plasma samples: application to pharmacokinetic studies in rats. Aoki-Maki, K; Cortés-Arroyo, AR; Domínguez-Ramírez, AM; López, JR; López-Muñoz, FJ; Peña, MH; Ríos-Castañeda, C, 2006)	0.83
"To assess the use of a von Frey device as a mechanical nociceptive stimulus for evaluation of the antinociceptive effects of morphine in dogs and its potential application in the pharmacodynamic modeling of morphine in that species."	( Assessment of a von Frey device for evaluation of the antinociceptive effects of morphine and its application in pharmacodynamic modeling of morphine in dogs. KuKanich, B; Lascelles, BD; Papich, MG, 2005)	0.76
" Finally, we tested several pharmacokinetic models, assuming first-order or capacity-limited processes at each brain interface, to describe experimental morphine and M6G concentrations previously obtained in rat plasma and brain fluids."	( Carrier-mediated processes at several rat brain interfaces determine the neuropharmacokinetics of morphine and morphine-6-beta-D-glucuronide. Bourasset, F; Scherrmann, JM, 2006)	0.75
"To develop an integrated population pharmacokinetic model for heroin (diamorphine) and its pharmacodynamically active metabolites 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide."	( Population pharmacokinetics of heroin and its major metabolites. Beijnen, JH; Huitema, AD; Rook, EJ; van den Brink, W; van Ree, JM, 2006)	0.57
" The present study is the first comprehensive pharmacokinetic analysis for any analgesic in an ectotherm, and our results show that: 1) significant intra-specific variation exists between fishes: and 2) the disposition of morphine in fish is approximately one order of magnitude slower than it is in mammals."	( Pharmacokinetics of morphine in fish: winter flounder (Pseudopleuronectes americanus) and seawater-acclimated rainbow trout (Oncorhynchus mykiss). Gamperl, K; Mendonça, PC; Newby, NC; Stevens, ED, 2006)	0.84
"We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty."	( Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty. Bourget, P; Chauvin, M; Fischler, M; Fletcher, D; Langlois, M; Manoir, BD; Paci, A; Szekely, B, 2006)	0.8
" The pharmacokinetic study revealed a limited and slow absorption of morphine."	( Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty. Bourget, P; Chauvin, M; Fischler, M; Fletcher, D; Langlois, M; Manoir, BD; Paci, A; Szekely, B, 2006)	0.8
" Pharmacokinetic findings were compared with those from a previous study in infants after noncardiac major surgery."	( Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane oxygenation in neonates. Anderson, BJ; Peters, JW; Simons, SH; Tibboel, D; Uges, DR, 2006)	1.78
" Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score."	( Pharmacokinetics and pharmacodynamics of morphine in llamas. Chapman, PL; Hellyer, PW; KuKanich, B; Mama, KR; Papich, MG; Uhrig, SR; Wagner, AE, 2007)	0.61
" A prolonged half-life was observed with IM injection."	( Pharmacokinetics and pharmacodynamics of morphine in llamas. Chapman, PL; Hellyer, PW; KuKanich, B; Mama, KR; Papich, MG; Uhrig, SR; Wagner, AE, 2007)	0.61
" Inclusion of covariates did not significantly decrease the nonlinear mixed-effects model objective function values and between-subject variability in the pharmacokinetic parameters of nested models."	( Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anderson, GD; Bradford, H; Chen, J; Ellenbogen, RG; Kantor, ED; Lynn, AM; Salinger, DH; Seng, KY; Vicini, P, 2007)	0.56
" The values of the pharmacodynamic parameters E(0), E(max), EC(50) and Hill factor were 45."	( Influence of biophase distribution and P-glycoprotein interaction on pharmacokinetic-pharmacodynamic modelling of the effects of morphine on the EEG. Bouw, MR; Danhof, M; de Lange, EC; de Mik, D; Freijer, J; Groenendaal, D, 2007)	0.54
" Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated."	( Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs. Guedes, AG; Papich, MG; Rider, MA; Rude, EP, 2007)	1.48
"The pharmacokinetic profile of M6G after oral administration was confirmed and with the presence of M3G and morphine in plasma after oral administration of M6G, proof seems to be found of the constant and prolonged absorption of M6G."	( Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers. Christrup, LL; Hansen, SH; Jensen, NH; Kristensen, K; Skram, U; Villesen, HH, 2007)	0.88
" Pharmacokinetic analysis showed no differences between male and female mice either for MOR or for NAL."	( Pharmacokinetic aspects of naloxone-precipitated morphine withdrawal in male and female prepubertal mice. Balerio, GN; Diaz, SL; Hermida, MP; Joannas, LD; Olivera, M; Ridolfi, A; Villaamil, EC, 2007)	0.59
" Pharmacokinetic and pharmacodynamic fitting was performed with the software NONMEM."	( Morphine in postoperative patients: pharmacokinetics and pharmacodynamics of metabolites. Butscher, K; Mazoit, JX; Samii, K, 2007)	1.78
" The pharmacokinetic findings are compatible with a more rapid and extensive initial effect of IV morphine compared with IM."	( Serum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery. Borchgrevink, PC; Dale, O; Klepstad, P; Nilsen, T; Thoner, J; Tveita, T, 2007)	0.85
" Pharmacokinetic parameters were calculated from the data, including maximum plasma concentration (Cmax), time to maximum concentration (Tmax), and area under plasma concentration-time curve (AUC), among others."	( Does intraosseous equal intravenous? A pharmacokinetic study. Burris, HA; Kuhn, JG; Miller, LJ; Von Hoff, DD, 2008)	0.35
", Stamford, CT) from the market after pharmacokinetic data revealed a risk of alcohol-induced dose-dumping prompted a re-examination of the risk-benefit profiles of extended-release drugs."	( Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules. Johnson, F; Stauffer, J; Sun, S; Wagner, G, 2008)	0.57
" This study was carried out to assess the efficacy, safety and pharmacokinetic profiles of a 12."	( Efficacy, safety and pharmacokinetic study of a novel fentanyl-containing matrix transdermal patch system in Japanese patients with cancer pain. Hanaoka, K; Hosokawa, T; Ishida, T; Kitajima, T; Mashimo, S; Miyazaki, T; Namiki, A; Nogami, S; Ogawa, S, 2008)	0.35
" The proposed method was successfully applied to the preliminarily study of potential pharmacokinetic interaction between Mor and diclofenac."	( Sensitive HPLC-fluorescence detection of morphine labeled with DIB-Cl in rat brain and blood microdialysates and its application to the preliminarily study of the pharmacokinetic interaction between morphine and diclofenac. Kuroda, N; Nakashima, K; Ogata, Y; Wada, M; Yamada, H; Yokota, C, 2008)	0.61
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
" Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated."	( Pharmacokinetics and physiological effects of intravenous hydromorphone in conscious dogs. Guedes, AG; Papich, MG; Rider, MA; Rude, EP, 2008)	0.35
" This pharmacodynamic phenomenon is referred to in the present work as "teleantagonism"."	( Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron. Cunha, FQ; Duarte, DB; Ferrari, LF; Ferreira, SH; Funez, MI; Lorenzetti, BB; Parada, CA; Sachs, D, 2008)	0.35
" This review highlights potential pharmacokinetic (changes in metabolite production, metabolizing enzyme expression, and transporter function) and pharmacodynamic (receptor type, location and functionality; alterations in signaling pathways and cross-tolerance) aspects of opioid tolerance development, and presents several pharmacodynamic modeling strategies that have been used to characterize time-dependent attenuation of opioid analgesia."	( Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. Dumas, EO; Pollack, GM, 2008)	0.35
" The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate."	( Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: application to a clinical pharmacokinetic study. Deng, Y; Liao, Q; Pan, B; Xie, Z; Zhang, L, 2009)	0.61
" Size is the primary covariate and although lean body weight is argued as a better measure than total body weight, the use of different fractions of fat mass to explain how pharmacokinetic parameters vary with body composition has been proposed."	( Mechanistic basis of using body size and maturation to predict clearance in humans. Anderson, BJ; Holford, NH, 2009)	0.35
" The elimination half-life was 140."	( Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancer. Ghandforoush-Sattari, M; Hain, RD; Mashayekhi, SO; Routledge, PA, 2009)	0.61
" The higher dose group produced a greater exposure (higher area-under-the-curve), higher peak concentration, longer half-life and a shorter time to peak concentration (t(max))."	( Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs. Aragon, CL; Barnhart, MD; Gaynor, JS; Papich, MG; Read, MR; Wilson, D, 2009)	0.6
" Morphine pharmacodynamic was best described by an indirect response model with an inhibitory function affecting pain onset, and it showed that decreasing delay between extubation and titration, decreasing initial VAS and intra-operative non-steroidal anti-inflammatory drug resulted in increased morphine potency."	( Intravenous morphine titration in immediate postoperative pain management: population kinetic-pharmacodynamic and logistic regression analysis. Abou Hammoud, H; Aubrun, F; Lechat, P; Riou, B; Simon, N; Urien, S, 2009)	1.64
" Using labeled doses of extended-release epidural morphine sulfate (10-20 mg), the C(max) was comparable to that for 5-mg standard epidural morphine sulfate, whereas the apparent terminal elimination half-life and area under the serum concentration-time curve were twofold to fourfold greater and consistent with dose-proportional exposure."	( Pharmacokinetics of extended-release epidural morphine sulfate: pooled analysis of six clinical studies. Gambling, DR; Hughes, TL; Manvelian, GZ; Viscusi, ER, 2009)	0.86
" Extended-release epidural morphine sulfate displayed a consistent pharmacokinetic profile among adults, with only slight variability between men and women in C(max), which appeared to be mainly caused by differences in body weight."	( Pharmacokinetics of extended-release epidural morphine sulfate: pooled analysis of six clinical studies. Gambling, DR; Hughes, TL; Manvelian, GZ; Viscusi, ER, 2009)	0.91
"During orthopaedic surgery of the limb, we performed a prospective, double blind controlled study on three parallel groups in 30 patients to evaluate the pharmacokinetic and pharmacodynamic effect of infiltration of the iliac crest bone graft harvest site with 20 ml of bupivacaine (100 mg), ropivacaine (150 mg) or saline as control group (n = 10 in each group)."	( Local anaesthetic use for the iliac crest-donor site: pharmacokinetic and pharmacodynamic evaluations. Chevanne, F; Ecoffey, C; Eliat, C; Estebe, JP; Husson, JL; Le Corre, P; Le Naoures, A, 2009)	0.35
"The primary objective was to compare the serum pharmacokinetic profile of a single dose of extended-release epidural morphine (EREM) administered alone versus 15 to 60 mins after an analgesic epidural dose of bupivacaine."	( Extended-release epidural morphine (DepoDur) following epidural bupivacaine in patients undergoing lower abdominal surgery: a randomized controlled pharmacokinetic study. Gambling, DR; Hughes, TL; Manvelian, GZ, )	0.64
" Median time to maximum serum concentration and median apparent terminal elimination half-life were also comparable."	( Extended-release epidural morphine (DepoDur) following epidural bupivacaine in patients undergoing lower abdominal surgery: a randomized controlled pharmacokinetic study. Gambling, DR; Hughes, TL; Manvelian, GZ, )	0.43
"The pharmacokinetic and efficacy profiles of a single 15-mg dose of EREM were not significantly altered when administered 15, 30, or 60 mins after an analgesic epidural dose of bupivacaine."	( Extended-release epidural morphine (DepoDur) following epidural bupivacaine in patients undergoing lower abdominal surgery: a randomized controlled pharmacokinetic study. Gambling, DR; Hughes, TL; Manvelian, GZ, )	0.43
" For the pharmacodynamic study, baseline levels for hyperalgesia and allodynia were taken for 5 days prior to surgery."	( Pharmacokinetics of vanillin and its effects on mechanical hypersensitivity in a rat model of neuropathic pain. Beaudry, F; Lema, PP; Ross, A; Vachon, P, 2010)	0.36
"The primary objective was to evaluate the serum pharmacokinetic profile of a single 15-mg dose of extended-release epidural morphine (EREM) administered at the lower thoracic epidural space alone or following a lidocaine-epinephrine test dose in patients undergoing major upper abdominal surgery."	( A randomized study of the serum pharmacokinetics of lower thoracic extended-release epidural morphine (DepoDur) after lidocaine-epinephrine test dose administration in patients undergoing upper abdominal surgery. Manvelian, GZ; Viscusi, ER, 2009)	0.78
" Noncompartmental pharmacokinetic parameters were determined based on the serum concentration-time profiles of morphine and morphine metabolites."	( A randomized study of the serum pharmacokinetics of lower thoracic extended-release epidural morphine (DepoDur) after lidocaine-epinephrine test dose administration in patients undergoing upper abdominal surgery. Manvelian, GZ; Viscusi, ER, 2009)	0.78
"The intent-to-treat and safety populations included 39 patients; the pharmacokinetic population included 37 patients."	( A randomized study of the serum pharmacokinetics of lower thoracic extended-release epidural morphine (DepoDur) after lidocaine-epinephrine test dose administration in patients undergoing upper abdominal surgery. Manvelian, GZ; Viscusi, ER, 2009)	0.57
"Plasma morphine concentrations were lower in the STZ-diabetic rats than controls although the elimination half-life of morphine was similar in the two groups (47."	( The pharmacokinetics of morphine and its glucuronide conjugate in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2B1 in the liver. Fukushima, S; Hasegawa, Y; Inotsume, N; Ishii, Y; Kishimoto, S; Nomura, H; Onishi, M; Shibatani, N; Takeuchi, Y, 2010)	1.12
" In addition, after the simultaneous administration of the drugs in a single dose, a pharmacokinetic interaction was found, which significantly (P<0."	( Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats. Cortés-Arroyo, AR; Domínguez-Ramírez, AM; López, JR; López-Muñoz, FJ; Y de la Peña, MH, 2010)	0.67
" Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhibitors."	( 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain. Hammock, BD; Inceoglu, B; Jones, PD; Liu, JY; Morisseau, C; Rose, TE; Sanborn, JR, 2010)	0.36
" Plasma samples were collected just before dosing through 72 hours postdose for pharmacokinetic analyses of morphine, and through 168 hours postdose for naltrexone and its major metabolite 6-β-naltrexol."	( Food effects on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, F; Stauffer, J; Swearingen, D, 2010)	0.84
" In this study, the predictive performance of a previously published paediatric population pharmacokinetic model for morphine and its metabolites in children younger than 3 years (original model) is studied in new datasets that were not used to develop the original model."	( Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Choonara, I; Danhof, M; DeJongh, J; Knibbe, CA; Krekels, EH; Lynn, AM; Tibboel, D; van der Marel, CD; van Lingen, RA, 2011)	0.8
" Basic observed versus predicted plots, normalized prediction distribution error analysis, model refitting, bootstrap analysis, subpopulation analysis and a literature comparison of clearance predictions were performed with the new datasets to evaluate the predictive performance of the original morphine pharmacokinetic model."	( Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Choonara, I; Danhof, M; DeJongh, J; Knibbe, CA; Krekels, EH; Lynn, AM; Tibboel, D; van der Marel, CD; van Lingen, RA, 2011)	0.77
"The predictive value of the original morphine pharmacokinetic model is demonstrated in new datasets by the use of six different validation and evaluation tools."	( Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Choonara, I; Danhof, M; DeJongh, J; Knibbe, CA; Krekels, EH; Lynn, AM; Tibboel, D; van der Marel, CD; van Lingen, RA, 2011)	0.87
" There are circumstances when a pharmacokinetic study may not be possible in children (especially neonates and infants), and as a result one would like to predict drug clearance in children."	( Evaluation of a morphine maturation model for the prediction of morphine clearance in children: how accurate is the predictive performance of the model? Mahmood, I, 2011)	0.72
" There were no significant differences between group CON and the other pretreatment groups in pharmacokinetic parameters taking both sexes into account."	( The influence of modulation of P-glycoprotein and /or cytochrome P450 3A on the pharmacokinetics and pharmacodynamics of orally administered morphine in dogs. Croubels, S; Gadeyne, C; Gasthuys, F; Polis, I; Schauvliege, S; Van der Heyden, S, 2011)	0.57
" USCPACK software was used to fit candidate pharmacokinetic models."	( Increased clearance of morphine in sickle cell disease: implications for pain management. Darbari, DS; Neely, M; Rana, S; van den Anker, J, 2011)	0.68
" Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6-MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice."	( Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice. Andersen, JM; Boix, F; Mørland, J, 2013)	0.59
"As a consequence of a continuous demand for increased throughput of pharmacokinetic (PK) studies, industries have introduced strategies to reduce the number of samples such as cassette analysis (pooling of samples after the in-life phase)."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
" This open-label, single-dose, 4-way crossover, pharmacokinetic drug interaction study compared the relative bioavailability of morphine and naltrexone when MS-sNT is administered (under fasting conditions) with increasing doses of alcohol."	( Effects of alcohol on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, FK; Kisicki, J; Stauffer, J, 2012)	0.84
" In this study, we sought to determine the pharmacokinetic and drug effects of prior epidural lidocaine administration on EREM."	( Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur®) after cesarean delivery. Atkinson Ralls, L; Carvalho, B; Clavijo, CF; Drover, DR, 2011)	0.59
" Maximal concentration (Cmax), time to Cmax (Tmax), and AUC(0-last) (area under the concentration-time curve until the last plasma concentration that was below the limit of quantitation) for morphine levels were determined from a plasma sample at 0, 5, 10, 15, and 30 minutes, and 1, 4, 8, 12, 24, 36, 48, and 72 hours."	( Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur®) after cesarean delivery. Atkinson Ralls, L; Carvalho, B; Clavijo, CF; Drover, DR, 2011)	0.78
"Epidural lidocaine administration (20-35 mL) 1 hour before epidural EREM administration increased the Cmax in group E (11."	( Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur®) after cesarean delivery. Atkinson Ralls, L; Carvalho, B; Clavijo, CF; Drover, DR, 2011)	0.59
" The oral pharmacodynamic study assessed drug liking and euphoria and pharmacokinetic properties of MS-sNTC and MS-sNTW compared with morphine sulfate solution (MSS) and placebo."	( Morphine sulfate and naltrexone hydrochloride extended-release capsules: naltrexone release, pharmacodynamics, and tolerability. Johnson, F; Setnik, B, )	1.78
"The main pharmacokinetic parameters of morphine by inhaled and intravenous administration were: MRT 59±14 min versus 19±4 min, T(1/2) 21."	( The pharmacokinetics of inhaled morphine delivered by an ultrasonic nebulizer in ventilated dogs. Ge, W; Pan, L; Wang, X; Xu, X; Zheng, M, 2012)	0.93
" Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic properties under diabetic conditions, specifically focusing on the involvement of intestinal P-gp in a type 1 diabetic mouse model."	( [Altered intestinal P-glycoprotein expression levels affect pharmacodynamics under diabetic condition]. Fujita-Hamabe, W; Kisioka, S; Nawa, A; Tokuyama, S, 2012)	0.62
" Commonly used approaches are physiologically-based pharmacokinetic modeling (PBPK) and allometric scaling (AS) in combination with maturation of clearance for early life."	( First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development. Danhof, M; Eissing, T; Freijer, J; Strougo, A; Willmann, S; Yassen, A, 2012)	0.38
"Intensive sampling of patients for drugs with complex pharmacokinetic profiles is difficult to perform in the clinic or hospitalized patient setting."	( The influence of sparse data sampling on population pharmacokinetics: a post hoc analysis of a pharmacokinetic study of morphine in healthy volunteers. Ariano, RE; Duke, PC; Sitar, DS, 2012)	0.59
"This study investigated whether population-guided, sparse-sampling pharmacokinetic analysis of morphine in 14 healthy volunteers allowed for optimal characterization of concentration-time profiles for a validation population of 5 young male patients receiving morphine."	( The influence of sparse data sampling on population pharmacokinetics: a post hoc analysis of a pharmacokinetic study of morphine in healthy volunteers. Ariano, RE; Duke, PC; Sitar, DS, 2012)	0.81
" These results were compared with traditional standard 2-stage (STS) pharmacokinetic modeling."	( The influence of sparse data sampling on population pharmacokinetics: a post hoc analysis of a pharmacokinetic study of morphine in healthy volunteers. Ariano, RE; Duke, PC; Sitar, DS, 2012)	0.59
" NPAG modeling identified that intravenous morphine was best represented by a 3-compartment pharmacokinetic profile and that sparse sampling with a least 3 blood samples per subject resulted in virtually identical measures of central tendency as the more intensively sampled dataset."	( The influence of sparse data sampling on population pharmacokinetics: a post hoc analysis of a pharmacokinetic study of morphine in healthy volunteers. Ariano, RE; Duke, PC; Sitar, DS, 2012)	0.85
"This post hoc analysis suggests that intensive sampling for discerning complex, 3-compartment pharmacokinetic models, such as morphine, may not be necessary."	( The influence of sparse data sampling on population pharmacokinetics: a post hoc analysis of a pharmacokinetic study of morphine in healthy volunteers. Ariano, RE; Duke, PC; Sitar, DS, 2012)	0.79
" Noncompartmental pharmacokinetic analysis and genotyping for 28 polymorphisms in eight genes (UGT1A8, UGT2B7, ABCB1, COMT, STAT6, MC1R, OPRM1, and ARRB2) were performed."	( Is ethnicity associated with morphine's side effects in children? Morphine pharmacokinetics, analgesic response, and side effects in children having tonsillectomy. Anderson, GD; Farin, FM; Jimenez, N; Lynn, AM; Nielsen, SS; Seidel, K; Shen, DD, 2012)	0.67
"A whole-body physiologically based pharmacokinetic (PBPK) model was developed for the prediction of unbound drug concentration-time profiles in the rat brain, in which drug transfer across the blood-brain barrier (BBB) was treated mechanistically by separating the parameters governing the rate (permeability) of BBB transfer from brain binding."	( Development of a physiologically based pharmacokinetic model for the rat central nervous system and determination of an in vitro-in vivo scaling methodology for the blood-brain barrier permeability of two transporter substrates, morphine and oxycodone. Ball, K; Bouzom, F; Declèves, X; Scherrmann, JM; Walther, B, 2012)	0.56
" Al-though size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented."	( Morphine clearance in children: does race or genetics matter? Chidambaran, V; Esslinger, HR; Fukuda, T; Krekels, EH; Ngamprasertwong, P; Sadhasivam, S; Vinks, AA; Zhang, K, )	1.81
"Genotype blinded clinical observational pharmacokinetic study."	( Morphine clearance in children: does race or genetics matter? Chidambaran, V; Esslinger, HR; Fukuda, T; Krekels, EH; Ngamprasertwong, P; Sadhasivam, S; Vinks, AA; Zhang, K, )	1.57
"Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races."	( Morphine clearance in children: does race or genetics matter? Chidambaran, V; Esslinger, HR; Fukuda, T; Krekels, EH; Ngamprasertwong, P; Sadhasivam, S; Vinks, AA; Zhang, K, )	3.02
" In this review, we explore advantages and disadvantages of the different data analysis techniques that have been applied, with specific focus on the accuracy of morphine clearance predictions by reported paediatric pharmacokinetic models."	( Prediction of morphine clearance in the paediatric population : how accurate are the available pharmacokinetic models? Danhof, M; Knibbe, CA; Krekels, EH; Tibboel, D, 2012)	0.94
" In order to optimize conditions for measuring heroin and its metabolites in samples collected for pharmacokinetic studies in rats, we investigated the time course of degradation of heroin, 6-MAM, and morphine in four biological matrices: rat blood, rat brain homogenate, bovine serum, and human plasma under various conditions."	( Stability of heroin, 6-monoacetylmorphine, and morphine in biological samples and validation of an LC-MS assay for delayed analyses of pharmacokinetic samples in rats. Birnbaum, AK; Harmon, TM; Jones, JM; Keyler, DE; Pentel, PR; Raleigh, MD; Remmel, RP, 2013)	0.86
"The in vivo preclinical pharmacodynamic profile of TD-1211, a selective opioid receptor antagonist currently under development for the treatment of opioid-induced constipation, was compared to that of the clinically studied opioid antagonists, naltrexone, alvimopan, and ADL 08-0011 (the primary active metabolite of alvimopan)."	( The in vivo pharmacodynamics of the novel opioid receptor antagonist, TD-1211, in models of opioid-induced gastrointestinal and CNS activity. Armstrong, SR; Beattie, DT; Campbell, CB; Hegde, SS; Long, DD; Richardson, CL; Tsuruda, PR; Vickery, RG, 2013)	0.39
"To compare the pharmacodynamic effects, including self-reports of "drug liking" and "high," of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules (MSN), crushed morphine sulfate controlled-release (CR) tablets, and placebo in an abuse potential study."	( Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreation Goli, V; Han, L; Setnik, B; Sommerville, K; Webster, L, 2013)	0.83
"Subjective ratings (100-point visual analog scales) of positive drug effects (drug liking, high, good effects, take drug again, and overall drug liking), any effects, and negative effects (bad effects, feel sick, nausea, sleepy, and dizzy), along with pupillometry, pharmacokinetic (PK), and safety assessments."	( Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreation Goli, V; Han, L; Setnik, B; Sommerville, K; Webster, L, 2013)	0.62
" PK analysis of morphine plasma concentrations indicated that Cmax was significantly lower and tmax significantly longer for crushed MSN compared with crushed morphine sulfate CR."	( Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreation Goli, V; Han, L; Setnik, B; Sommerville, K; Webster, L, 2013)	0.96
" In preliminary investigations, samples were obtained from 2 healthy horses at 12 time points (up to 12 hours after drug administration) and analyzed via 2-stage pharmacokinetic analysis."	( Pharmacokinetics of intramuscularly administered morphine in horses. Beard, WL; Devine, EP; KuKanich, B, 2013)	0.64
" Population pharmacokinetic analysis characterized the profiles in NONMEM(®) and tested OCT1 variants as covariates."	( OCT1 genetic variants influence the pharmacokinetics of morphine in children. Chidambaran, V; Esslinger, HR; Fukuda, T; Mizuno, T; Ngamprasertwong, P; Olbrecht, V; Sadhasivam, S; Venkatasubramanian, R; Vinks, AA, 2013)	0.64
" We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone."	( Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine or methadone. Ashley, CC; Carlyn, C; Fontenelle, DV; Fudin, HR; Fudin, J; Hinden, DA, 2013)	0.84
" A pharmacokinetic study was then carried out in three groups with CYP2D6*1/*1 (n=10), CYP2D6*1/*10 (n=10) and CYP2D6*10/*10 (n=9) genotypes by collecting serial blood samples for determination of plasma levels of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine phosphate."	( The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects. Guo, T; Lv, J; Wu, X; Yuan, L; Zuo, J, 2014)	0.58
"No significant differences were observed in the pharmacokinetic parameters of codeine in the three genotype groups."	( The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects. Guo, T; Lv, J; Wu, X; Yuan, L; Zuo, J, 2014)	0.4
" The association between pharmacokinetic parameters and treatment response was assessed using logistic regression."	( Population pharmacokinetics of nefopam in elderly, with or without renal impairment, and its link to treatment response. Djerada, Z; Fournet-Fayard, A; Gozalo, C; Lamiable, D; Lelarge, C; Malinovsky, JM; Millart, H, 2014)	0.4
"We identified the nefopam pharmacokinetic predictors for morphine requirement and side-effects, such as tachycardia and postoperative nausea and vomiting."	( Population pharmacokinetics of nefopam in elderly, with or without renal impairment, and its link to treatment response. Djerada, Z; Fournet-Fayard, A; Gozalo, C; Lamiable, D; Lelarge, C; Malinovsky, JM; Millart, H, 2014)	0.65
" The pharmacokinetic effect of morphine on plasma etoposide concentration after the oral concomitant use of etoposide and morphine in rats was assessed using a population analysis approach."	( Pharmacokinetic assessment of absorptive interaction of oral etoposide and morphine in rats. Iwanaga, K; Kakemi, M; Minamida, M; Miyazaki, M; Nishimura, C, 2014)	0.92
"When growing up, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of drugs change, which may alter the effect of drugs."	( Towards evidence-based dosing regimens in children on the basis of population pharmacokinetic pharmacodynamic modelling. Admiraal, R; Boelens, JJ; Bredius, RG; Knibbe, CA; Tibboel, D; van Kesteren, C, 2014)	0.4
" Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined."	( Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses. Knych, HK; McKemie, DS; Steffey, EP, 2014)	0.69
"The aim of this study was to evaluate the clinical pharmacokinetics of morphine (M) and their correlation with pharmacodynamic results (effective daily dose of M and side effects) during the M titration phase, in the management of chronic cancer pain."	( Clinical pharmacokinetics of morphine and its metabolites during morphine dose titration for chronic cancer pain. Allegri, M; De Gregori, M; De Gregori, S; Govoni, S; Minella, CE; Ranzani, GN; Regazzi, M; Tinelli, C, 2014)	0.93
"This article presents the pharmacokinetic profiles of M and its metabolites: their concentration ratio could help clinicians to optimize individual therapies and tailor the dose to individual needs."	( Clinical pharmacokinetics of morphine and its metabolites during morphine dose titration for chronic cancer pain. Allegri, M; De Gregori, M; De Gregori, S; Govoni, S; Minella, CE; Ranzani, GN; Regazzi, M; Tinelli, C, 2014)	0.69
"This paper aimed to evaluate the effects of coadministered immediate-release morphine and ethanol on safety, pharmacokinetic, and pharmacodynamic measures."	( Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants. Johnson, F; Oldenhof, J; Romach, M; Setnik, B; Sokolowska, M, 2014)	0.84
" Safety, pharmacodynamic (including visual analog scales, pupillometry, capnography, and psychomotor and cognitive measures), and pharmacokinetic assessments were conducted."	( Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants. Johnson, F; Oldenhof, J; Romach, M; Setnik, B; Sokolowska, M, 2014)	0.61
" No consistent additive or interaction effects were observed on pharmacodynamic measures."	( Evaluation of the safety, pharmacodynamic, and pharmacokinetic effects following oral coadministration of immediate-release morphine with ethanol in healthy male participants. Johnson, F; Oldenhof, J; Romach, M; Setnik, B; Sokolowska, M, 2014)	0.61
" These doses were used to estimate the individual pharmacokinetic parameters by the Bayesian method using a linear 2-compartment model with a first-order kinetic absorption and the population parameters reported in our previous study."	( Pharmacokinetics and toxicity of repeated oral etoposide is altered by morphine coadministration in rats. Iwanaga, K; Kakemi, M; Kawase, T; Kitamura, T; Miyazaki, M; Nishimura, C, 2015)	0.65
" Therefore, we aimed to study the pharmacokinetics of oral morphine in morbidly obese patients before and after RYGB surgery, to identify the effects of RYGB and the subsequent reversal of morbid obesity on the pharmacokinetic parameters of morphine."	( Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach. Bardin, C; Bergmann, JF; Bouillot, JL; Chast, F; Declèves, X; Hirt, D; Lloret-Linares, C; Mouly, S; Oppert, JM; Poitou, C; Scherrmann, JM, 2014)	0.88
" A population pharmacokinetic model was used to describe the time course of the plasma morphine concentration, to study the effect of RYGB on morphine pharmacokinetics and to estimate inter-patient variability."	( Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach. Bardin, C; Bergmann, JF; Bouillot, JL; Chast, F; Declèves, X; Hirt, D; Lloret-Linares, C; Mouly, S; Oppert, JM; Poitou, C; Scherrmann, JM, 2014)	0.86
" Pharmacodynamic measures were limited to subject assessment of somnolence, dizziness, and nausea conducted by using a visual analog scale (VAS)."	( Gabapentin enacarbil and morphine administered in combination versus alone: a double-blind, randomized, pharmacokinetic, and tolerability comparison. Arumugham, T; Chen, C; Davy, M; Stier, B; Upward, J, 2015)	0.72
"No significant pharmacokinetic interaction between the 2 drugs was seen in this study."	( Gabapentin enacarbil and morphine administered in combination versus alone: a double-blind, randomized, pharmacokinetic, and tolerability comparison. Arumugham, T; Chen, C; Davy, M; Stier, B; Upward, J, 2015)	0.72
" The aims were: (1) to develop a population pharmacokinetic model of liquid rectal morphine and morphine-6-glucoronide (M6G), (2) to simulate clinically relevant rectal doses of morphine and (3) to assess the tolerability and safety."	( Population pharmacokinetics of morphine and morphine-6-glucuronide following rectal administration--a dose escalation study. Brokjær, A; Christrup, LL; Dahan, A; Drewes, AM; Kreilgaard, M; Olesen, AE; Simonsson, US, 2015)	0.93
"A population pharmacokinetic model of liquid rectal morphine and M6G was developed."	( Population pharmacokinetics of morphine and morphine-6-glucuronide following rectal administration--a dose escalation study. Brokjær, A; Christrup, LL; Dahan, A; Drewes, AM; Kreilgaard, M; Olesen, AE; Simonsson, US, 2015)	0.95
" We aimed to develop a codeine pharmacokinetic pathway model for codeine and its metabolites that incorporates the effects of genetic polymorphisms."	( CYP2D6 phenotype-specific codeine population pharmacokinetics. Boston, RC; Daly Linares, AL; Fudin, J; Linares, OA; Schiesser, WE, 2015)	0.42
" Simulations were also used to examine the impact of effect-site equilibration half-life on time course of response."	( A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain. Christrup, LL; Drewes, AM; Kreilgaard, M; Lund, TM; Olesen, AE; Sverrisdóttir, E, 2015)	0.8
" Published pharmacokinetic data of acetaminophen in subjects with normal gastric emptying vs."	( Acetaminophen absorption kinetics in altered gastric emptying: establishing a relevant pharmacokinetic surrogate using published data. Srinivas, NR, 2015)	0.42
" A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM."	( Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery. Drover, DR; Elkomy, MH; Frymoyer, A; Galinkin, JL; Glotzbach, KL; Hammer, GB; Su, F, 2016)	0.76
" The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies."	( Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium. Gauda, E; Gobburu, J; Ivaturi, V; Lewis, T; Liu, T, 2016)	0.95
" To determine the pharmacokinetics of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in this population, and to find clinically relevant parameters for dose individualisation, we performed a population pharmacokinetic analysis."	( Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients. Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Masman, AD; Mathot, RA; Tibboel, D; van Gelder, T, 2016)	1.03
" Nonlinear mixed-effects modelling (NONMEM) was used to develop a population pharmacokinetic model and perform covariate analysis."	( Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients. Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Masman, AD; Mathot, RA; Tibboel, D; van Gelder, T, 2016)	0.76
" In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed."	( Abuse-Deterrent Opioid Formulations: Pharmacokinetic and Pharmacodynamic Considerations. Knothe, C; Lötsch, J; Walter, C, 2016)	0.43
" The pharmacokinetic parameters of morphine and its glucuronides were not associated with the jejunal contents of P-gp, CYP3A4, MRP2, and MRP3."	( Oral Morphine Pharmacokinetic in Obesity: The Role of P-Glycoprotein, MRP2, MRP3, UGT2B7, and CYP3A4 Jejunal Contents and Obesity-Associated Biomarkers. Bergmann, JF; Bouillot, JL; Declèves, X; Labat, L; Laplanche, JL; Lloret-Linares, C; Luo, H; Miyauchi, E; Mouly, S; Oppert, JM; Poitou, C; Scherrmann, JM; Tachikawa, M; Terasaki, T; Uchida, Y, 2016)	1.23
" Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.68
"In endotoxemia, decreased elimination half-life (P = 0."	( Effects of Low-Dose Escherichia coli Lipopolysaccharide-Induced Endotoxemia on Morphine Pharmacokinetics in an Animal Model. Billert, H; Grabowski, T; Grześkowiak, E; Lisiecka, J; Michalak, M; Szkutnik-Fiedler, D; Urjasz, H, 2016)	0.66
"This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination."	( Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol. Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Mathôt, RA; Tibboel, D; van Esch, HJ; van Gelder, T; van Zuylen, L, 2016)	0.66
"Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic study."	( Pharmacodynamic Analysis of Morphine Time-to-Remedication Events in Infants and Young Children After Congenital Heart Surgery. Drover, DR; Elkomy, MH; Galinkin, JL; Glotzbach, KL; Hammer, GB, 2016)	0.99
"We used the intestinal segregated flow model (SFM) versus the traditional model (TM), nested within physiologically based pharmacokinetic (PBPK) models, to describe the biliary and urinary excretion of morphine 3β-glucuronide (MG) after intravenous and intraduodenal dosing of morphine in rats in vivo."	( Metabolite Kinetics: The Segregated Flow Model for Intestinal and Whole Body Physiologically Based Pharmacokinetic Modeling to Describe Intestinal and Hepatic Glucuronidation of Morphine in Rats In Vivo. Chen, S; Fan, J; Liu, L; Pang, KS; Sun, H; Yang, QJ, 2016)	0.81
" Rapid absorption, linear pharmacokinetics up to 1000 mg, and low to moderate between-subject pharmacokinetic variability was observed."	( Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending-dose study. Bui, K; Butler, K; Eldon, MA; Kugler, AR; Medve, RA; Sostek, M, 2015)	0.42
" However, pharmacokinetic data to support morphine dosing in this vulnerable population are lacking."	( Decreased Morphine Clearance in Neonates With Hypoxic Ischemic Encephalopathy Receiving Hypothermia. Bonifacio, SL; Drover, DR; Frymoyer, A; Su, F; Van Meurs, KP; Wustoff, CJ, 2017)	1.12
" Consequently, a knowledge gap exists with regard to pharmacokinetic (PK) and pharmacodynamic (PD) responses in elderly subjects, leaving the safety and efficacy of medicines for this population unclear."	( Development of a Whole-Body Physiologically Based Pharmacokinetic Approach to Assess the Pharmacokinetics of Drugs in Elderly Individuals. Eissing, T; Jaehde, U; Krauss, M; Meyer, M; Schlender, JF; Thelen, K; Willmann, S, 2016)	0.43
"The goal of this study was to extend a physiologically based pharmacokinetic (PBPK) model for adults to encompass the full course of healthy aging through to the age of 100 years, to support dose selection and improve pharmacotherapy for the elderly age group."	( Development of a Whole-Body Physiologically Based Pharmacokinetic Approach to Assess the Pharmacokinetics of Drugs in Elderly Individuals. Eissing, T; Jaehde, U; Krauss, M; Meyer, M; Schlender, JF; Thelen, K; Willmann, S, 2016)	0.43
" Previously published population pharmacokinetic models of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were combined into a meta-model."	( Pharmacokinetic models of morphine and its metabolites in neonates:: Systematic comparisons of models from the literature, and development of a new meta-model. Foster, DJ; Knøsgaard, KR; Kreilgaard, M; Sverrisdóttir, E; Upton, RN; van den Anker, JN, 2016)	0.98
" Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions."	( Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat. Gabel-Jensen, C; Juul, RV; Kreilgaard, M; Lund, TM; Papathanasiou, T, 2016)	0.7
" The combination did not lead to pharmacokinetic interactions for morphine or gabapentin but resulted in an estimated ~33% diminished morphine-3-glucuronide formation."	( Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat. Gabel-Jensen, C; Juul, RV; Kreilgaard, M; Lund, TM; Papathanasiou, T, 2016)	0.94
"The finding of a lack of pharmacokinetic interaction strengthens the notion that the combination of the two drugs leads to better efficacy in pain treatment due to interaction at the pharmacodynamic level."	( Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat. Gabel-Jensen, C; Juul, RV; Kreilgaard, M; Lund, TM; Papathanasiou, T, 2016)	0.7
" Plasma samples were obtained for pharmacokinetic analysis."	( Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in Children With and Without Down Syndrome. Breatnach, CV; Calvier, EA; Casey, WF; Knibbe, CA; Krekels, EH; Mathôt, RA; O'Hare, BP; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2016)	0.7
" Population pharmacokinetic analysis revealed no statistically significant differences in any of the pharmacokinetic variables of morphine between the children with and without Down syndrome."	( Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in Children With and Without Down Syndrome. Breatnach, CV; Calvier, EA; Casey, WF; Knibbe, CA; Krekels, EH; Mathôt, RA; O'Hare, BP; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2016)	0.9
" The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist."	( Metabolism and pharmacokinetics of morphine in neonates: A review. Pacifici, GM, 2016)	1.23
" PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2)."	( Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model. Arias, RS; Brown, RH; Dalesio, NM; Galinkin, J; Hendrix, CW; Lee, CK; Lynn, RR; McMichael, DH; Pho, H; Schwartz, AR; Thompson, CB; Yaster, M, 2016)	0.98
"To elucidate the pharmacokinetic component to the tolerance, we administered midazolam (2 mg/kg) and morphine (10 mg/kg) alone or their combination daily to rats for 12 days followed by a pharmacokinetic study on day 13."	( Pharmacokinetics cannot explain the increased effective dose requirement for morphine and midazolam in rats during their extended administration alone or in combination. Alam, SM; Blobner, M; Greenblatt, DJ; Mao, J; Martyn, JA; Schaller, SJ; Zhao, Y, 2017)	0.9
" To further explore the underlying mechanisms for variability arising from relevant determinants, including OCT1, a physiologically based pharmacokinetic (PBPK) model of morphine was developed."	( Characterization of Contributing Factors to Variability in Morphine Clearance Through PBPK Modeling Implemented With OCT1 Transporter. Emoto, C; Fukuda, T; Johnson, TN; Neuhoff, S; Sadhasivam, S; Vinks, AA, 2017)	0.89
"Pharmacokinetic and pharmacodynamic data were collected from a double-blinded, randomized, crossover trial in 37 healthy subjects."	( Lack of genetic association between OCT1, ABCB1, and UGT2B7 variants and morphine pharmacokinetics. Brøsen, K; Christrup, LL; Drewes, AM; Feddersen, S; Nielsen, LM; Olesen, AE; Stage, TB; Sverrisdóttir, E, 2017)	0.69
" Other pharmacokinetic interactions along with known pharmacodynamic interactions in which metamizol active metabolites contribute, should be considered."	( Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats. Carrillo-Calzadilla, PE; Cortés-Arroyo, AR; Domínguez-Ramírez, AM; López-Muñoz, FJ; Medina-López, JR; Moreno-Rocha, LA, 2017)	0.68
" A population pharmacokinetic (PopPK) analysis was performed to assess differences in morphine and morphine-3-glucuronide (M3G) disposition in NASH and healthy subjects."	( Population Pharmacokinetics of Morphine in Patients With Nonalcoholic Steatohepatitis (NASH) and Healthy Adults. Brouwer, K; Ferslew, BC; Gonzalez, D; Johnston, CK; Pierre, V, 2017)	0.96
" The purpose of this study was to quantitatively characterize the pharmacodynamic interaction between the two drugs and to identify the optimal concentration-effect relationship of the combination."	( Quantification of the Pharmacodynamic Interaction of Morphine and Gabapentin Using a Response Surface Approach. Gabel-Jensen, C; Heegaard, AM; Juul, RV; Kreilgaard, M; Lund, TM; Papathanasiou, T, 2017)	0.7
" Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human, and to predict drug concentration-time profiles in multiple CNS compartments on available human data of four drugs (acetaminophen, oxycodone, morphine and phenytoin)."	( Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. Beukers, MW; Danhof, M; de Lange, ECM; Huntjens, DR; Kokki, H; Kokki, M; Krauwinkel, W; Proost, JH; Välitalo, PA; van Hasselt, JGC; Vermeulen, A; Wong, YC; Yamamoto, Y, 2018)	0.66
" A physiologically based pharmacokinetic (PBPK) model was developed and applied to examine whether the morphine concentrations were (i) in agreement with the morphine doses documented in the clinical records or (ii) due to an excessive morphine administration."	( The feasibility of physiologically based pharmacokinetic modeling in forensic medicine illustrated by the example of morphine. Lehr, T; Moj, D; Ramsthaler, F; Schaefer, N; Schmidt, PH, 2018)	0.91
"Morphine has large pharmacokinetic variability, which is further complicated by developmental changes in neonates and small infants."	( PBPK Model of Morphine Incorporating Developmental Changes in Hepatic OCT1 and UGT2B7 Proteins to Explain the Variability in Clearances in Neonates and Small Infants. Emoto, C; Fukuda, T; Hahn, D; Johnson, TN; Neuhoff, S; Vinks, AA, 2018)	2.28
"The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness."	( Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review. Joynt, GM; Lee, A; Ling, L; Tse, AHW, 2018)	0.48
"The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine."	( Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses. Hamamoto-Hardman, BD; Kass, P; Knych, HK; McKemie, DS; Steffey, EP; Weiner, D, 2019)	0.97
" Our analysis demonstrates that body weight and postmenstrual age are relevant predictors of pharmacokinetic parameters of morphine and its metabolites."	( Morphine Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure: A Population Pharmacokinetic-Pharmacogenomic Study. Benitez, GR; Bradfield, J; Curley, MAQ; Gastonguay, MR; Gastonguay, MS; Hakonarson, H; Moorthy, G; Prodell, J; Zane, NR; Zuppa, AF, 2019)	2.16
" Bupivacaine administration by micropump nebulization resulted in a significantly lower Highest Plasma Drug Concentration (Cmax) and shorter time to reach Cmax (Tmax) (P < ."	( Population Pharmacokinetics of Intraperitoneal Bupivacaine Using Manual Bolus Atomization Versus Micropump Nebulization and Morphine Requirements in Young Children. Houck, CS; Meier, PM; Munoz-San Julian, C; Nguyen, HT; Pereira, LM; Zurakowski, D, 2019)	0.72
" The elimination half-life slowly improved over the following cycles suggesting a reversible cause responsible for reduced MTX clearance and toxicity during the first cycle."	( Reversible Impaired Methotrexate Clearance After Platinum-Based Chemotherapy for Osteosarcoma. de Haan, J; Oude Munnink, T; Touw, D; van der Meer, A; van Kruchten, M, 2019)	0.51
" Blood was collected at baseline and at subsequent preset times for pharmacokinetic analysis of morphine and its metabolites."	( Effects of Obstructive Sleep Apnea and Obesity on Morphine Pharmacokinetics in Children. Brown, RH; Clarke, W; Collaco, JM; Dalesio, NM; Hendrix, CW; Hsu, A; Kerns, N; Lee, CKK; McGrath-Morrow, S; Schwartz, AR; Yaster, M, 2020)	1.03
" Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group."	( Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy. Coetzee, JF; Hartnack, AK; Kleinhenz, MD; Lakritz, J; Niehaus, AJ, 2020)	0.8
"During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine."	( Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy. Coetzee, JF; Hartnack, AK; Kleinhenz, MD; Lakritz, J; Niehaus, AJ, 2020)	1.01
" The simultaneous quantification of morphine, fentanyl and its metabolites via this simple and time- and cost-efficient method could be successfully applied to samples taken for pharmacokinetic evaluation (antemortem and postmortem) after a single dose of morphine or co-administration of morphine with other drugs (e."	( Determination of Morphine, Fentanyl and Their Metabolites in Small Sample Volumes Using Liquid Chromatography Tandem Mass Spectrometry. Gleba, J; Kim, J, 2020)	1.17
" Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature."	( Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children. de Wildt, SN; Koenderink, JB; Litjens, CHC; Mathijssen, RHJ; Russel, FGM; Verbeek, MM; Verscheijden, LFM, 2021)	1.14
" Here, we describe the synthesis and pharmacodynamic and pharmacokinetic properties of the first constrained NTS2 macrocyclic NT(8-13) analog."	( Pharmacodynamic and pharmacokinetic profiles of a neurotensin receptor type 2 (NTS2) analgesic macrocyclic analog. Boudreault, PL; Chartier, M; Chevillard, L; Côté, J; Desgagné, M; Haroune, L; Longpré, JM; Marsault, É; Rumsby, C; Sarret, P; Sousbie, M; Théroux, L, 2021)	0.62
" Our modeling approach provides a promising platform for pharmacodynamic research of analgesics and sedatives in children."	( Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children. Ceelie, I; de Kluis, T; de Wildt, SN; Goulooze, SC; Knibbe, CAJ; Krekels, EHJ; Tibboel, D; van Dijk, M, 2022)	1
" Nebulized (NEB) morphine may represent an alternative for titration but pharmacokinetic (PK) properties of short nebulization using routine devices need evaluation."	( Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers. Aubrun, F; Duflot, T; Joannidès, R; Lamoureux, F; Lvovschi, VE; Pereira, T; Tavolacci, MP, 2022)	1.35
" Blood samples were collected up to 72 hours post administration, codeine, codeine 6-glucuronide, norcodeine morphine, morphine 3-glucuronide and M6G concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed."	( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses. Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022)	0.93
" The authors hypothesized that these opioids differ in their pharmacodynamic behavior, measured as effect on ventilation at an extrapolated end-tidal Pco2 at 55 mmHg, V̇E55."	( Respiratory Effects of Biased Ligand Oliceridine in Older Volunteers: A Pharmacokinetic-Pharmacodynamic Comparison with Morphine. Dahan, A; Demitrack, MA; Fossler, M; Jansen, S; Kuijpers, KWK; Michalsky, C; Nicklas, T; Niesters, M; Olofsen, E; Sarton, E; Simons, P; van der Schrier, R; van Lemmen, M; van Velzen, M, 2023)	1.12

Compound-Compound Interactions

Intrathecal dexmedetomidine has the least immunosuppressive effect than morphine. Tramadol (100 mg) given 30 min before abdominal hysterectomy resulted in improved analgesic efficacy.

Excerpt	Reference	Relevance
"Antitumor activity and lethality of cyclophosphamide alone and in combination with several drugs were investigated in male ddY mice."	( [Drug interaction on antitumor drugs I. Antitumor activity of cyclophosphamide in mice consecutively administered aminopyrine, chlorpromazine, or morphine (author's transl)]. Saitoh, M; Sasaki, K; Takayanagi, G, 1979)	0.46
"The antinociceptive effects of various cannabinoids, alone and in combination with opiates, were evaluated in antinociceptive tests in mice."	( Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. Stevens, DL; Welch, SP, 1992)	0.5
"Continuous Reaction Time (CRT) was measured in cancer patients receiving peripherally acting analgesics either alone (n = 16) or in combination with opioids (n = 16)."	( Reaction time in cancer patients receiving peripherally acting analgesics alone or in combination with opioids. Banning, A; Kaiser, F; Sjøgren, P, 1992)	0.28
"To examine the efficacy of intramuscular (IM) ketorolac used in combination with intravenous (IV) patient-controlled analgesia (PCA) morphine for postoperative pain relief following intra-abdominal gynecologic surgery."	( The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. Brull, SJ; Ning, T; Paige, D; Sevarino, FB; Silverman, DG; Sinatra, RS, )	0.56
"The analgesic effect of subarachnoid administration of tetracaine combined with low dose morphine or nalbuphine for spinal anesthesia was evaluated in 60 ASA physical status class I or II patients."	( [The analgesic effect of subarachnoid administration of tetracaine combined with low dose morphine or nalbuphine for spinal anesthesia]. Lin, ML, 1992)	0.73
"This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats."	( Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Cmielewski, PL; Cousins, MJ; Gourlay, GK; Owen, H; Plummer, JL, 1992)	0.78
"Lignocaine was tested either alone or in combination with a low dose of morphine by intrathecal administration on the C- and A-beta evoked responses of nociceptive neurones in the dorsal horn of the halothane-anaesthetized rat."	( Spinal local anaesthetic actions on afferent evoked responses and wind-up of nociceptive neurones in the rat spinal cord: combination with morphine produces marked potentiation of antinociception. Chapman, V; Dickenson, AH; Fraser, HM, 1992)	0.72
"Spinal anesthesia with 2% solution of lidocaine++ in combination with 1-1."	( [Evaluation of the effectiveness of spinal anesthesia using lidocaine combined with morphine]. Gel'tser, BI; Mazaev, VP; Semenikhin, AA; Shumatov, VB, 1990)	0.5
" In combination with D-Phe, a dose of morphine less by half compared to its unique use does not reduce analgesic activity in rats, but after six weeks of treatment some undesirable side effects like dependence, behavioural disorders and growth retardation are markedly lowered."	( [The analgesic action of d-phenylalanine in combination with morphine or methadone]. Dove, B; Göres, E; Morgenstern, E, 1991)	0.79
"Because only limited and controversial data exist concerning the respiratory effects of clonidine in humans, the authors evaluated the respiratory effects of clonidine alone and in combination with morphine, in 12 healthy adult males."	( Respiratory effects of clonidine alone and combined with morphine, in humans. Bailey, PL; East, KA; East, TD; Eldredge, SJ; Johnson, GK; Pace, NL; Sperry, RJ; Stanley, TH, 1991)	0.72
" The effects of cocaine alone and in combination with d-amphetamine, caffeine, morphine or delta-9-tetrahydrocannabinol were determined in five male white Carneaux pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 schedule (mult FR FI)."	( The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon. Evans, EB; Wenger, GR, 1990)	0.51
"1% end-tidal concentration) combined with epidurally administered morphine were compared during controlled ventilation in 10 dogs used on 2 occasions and randomly allocated to 2 groups."	( Comparison of the hemodynamic effects of halothane alone and halothane combined with epidurally administered morphine for anesthesia in ventilated dogs. Cockshutt, JR; Dyson, DH; McDonell, WN; Valliant, AE; Valverde, A, 1991)	0.73
" The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0."	( Drug interactions in the reinforcing effects of over-the-counter cough syrups. Masukawa, Y; Misawa, M; Suzuki, T, 1990)	0.28
" It is concluded that intrathecal morphine sulphate combined with elective forceps delivery provides a satisfactory alternative to epidural anaesthesia in those patients whose cardiovascular status demands preservation of a normal or elevated systemic vascular resistance."	( Low-dose intrathecal morphine sulphate as sole analgesic for pain of labour in combination with elective forceps delivery. A report of 10 cases. Boezaart, AP; Kadieva, VS, 1990)	0.88
" PTH 64-84 was inactive in all tests, alone or in combination with sCT or morphine."	( The activity of several peptide fragments of parathyroid hormone, alone and in combination with salmon calcitonin and morphine, in antinociceptive tests in the mouse. Dewey, WL; Welch, SP, 1990)	0.72
" Clonidine, given alone, had no effect; however, when administered with morphine it blocked the analgesic effect of morphine."	( Effects of clonidine and yohimbine, alone and in combination with morphine, on supraspinal analgesia. Izenwasser, S; Kornetsky, C, 1990)	0.75
"The efficacy of subarachnoidal anesthesia with lidocaine (trimecaine) in combination with small morphine doses was compared to anesthesia with lidocaine (trimecaine) alone."	( [Evaluation of subarachnoid anesthesia using local anesthetics in combination with morphine]. Mazaev, VP; Semenikhin, AA; Shumatov, VB, )	0.57
" Further investigations, using purified glycoproteins and structurally defined oligosaccharides, established that the optimal antigenic structure for both antibodies involves the Type 1 based blood group antigen, Lea, in combination with the Type 2 based onco-developmental antigen, SSEA-1, (Formula: see text) as in lacto-N-difucohexaose II."	( Novel antigenic specificity involving the blood group antigen, Lea, in combination with onco-developmental antigen, SSEA-1, recognized by two monoclonal antibodies to human milk-fat globule membranes. Feizi, T; Gooi, HC; Hilgers, J; Hilkens, J; Hounsell, EF; Jones, NJ; Scudder, P, 1985)	0.27
" The use of morphine alone or combined with slow release triamcinolone does not appear to be appropriate for the treatment of the post-laminectomy pain syndrome."	( Epidural steroids, epidural morphine and epidural steroids combined with morphine in the treatment of post-laminectomy syndrome. Frank, E; Gallo, JP; Kaul, AF; Lipson, SJ; Rocco, AG, 1989)	0.95
" The present study was conducted to investigate the effects of amfonelic acid, an indirect dopamine agonist, and nisoxetine, a highly selective norepinephrine uptake blocker, alone and in combination with morphine, on the reward threshold for rewarding electrical intracranial stimulation."	( The effect of amfonelic acid or nisoxetine in combination with morphine on brain-stimulation reward. Izenwasser, S; Kornetsky, C, 1989)	0.7
" The application of long-lasting local anaesthetics like bupivacaine in combination with morphine provides good conditions for postoperative pain relief following proctological operations."	( [Experiences with sacral anesthesia in combination with morphine analgesia]. Klug, W; Knoch, HG, 1989)	0.74
" The H1 blockers, including an ethylenediamine (pyrilamine), an ethanolamine (diphenhydramine), a phenothiazine (methdilazine), a piperazine (cyclizine) and an alkylamine (chlorpheniramine), all produced antinociception when given alone to mice and also caused potentiation when combined with morphine."	( Effect of H1 blockers alone and in combination with morphine to produce antinociception in mice. Hanig, JP; Hui, FW; Sun, CL, 1985)	0.7
"A series of agents were tested for their ability to interact with the analgetic actions of either d-amphetamine (d-AMP) or l-amphetamine (l-AMP), or morphine in rats using the hot plate procedure."	( Differential analgetic actions of amphetamine enantiomers in the mouse: a drug-drug interaction study. Maickel, RP; Spratto, GR; Tocco, DR, 1985)	0.47
" However, PCP in combination with morphine produced an increase in met-enkephalin levels and a decrease in HVA levels."	( Effects of phencyclidine in combination with morphine on the levels of met-enkephalin, dopamine, DOPAC and HVA in discrete brain areas of mice. Furukawa, H; Hiramatsu, M; Kameyama, T; Nabeshima, T, 1985)	0.81
" Studies revealed that tripelennamine (Tp) alone produced antinociception (ANTI) in mice and also caused potentiation when combined with morphine (M) or nalbuphene (NB)."	( The effect of tripelennamine alone and in combination with opiates to produce antinociception in mice. Hanig, JP; Hui, FW; Sun, CJ; Tocus, EC, 1983)	0.47
"The efficacy of spinal anesthesia with lidocaine (1 mg/kg) combined with moradol (0."	( [Spinal anesthesia with lidocaine combined with moradol]. Kheĭfets, VKh; Maksimov, AV, )	0.13
" Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine."	( Characteristics of the analgesic effects and drug interactions of intrathecal carbachol in rats. Abram, SE; O'Connor, TC, 1995)	0.53
"The purpose of the study was to compare the duration of analgesia and the amount of supplemental postoperative analgesics required when morphine combined with bupivacaine was injected into the knee joint at the end of knee arthroscopy surgery."	( Effects of tourniquet time in knee arthroscopy patients receiving intraarticular morphine combined with bupivacaine. Klinken, C, 1995)	0.72
" The use of TTS fentanyl in combination with initial dose titration using PCA resulted in rapid and statistically significant pain relief in both studies."	( Transdermal fentanyl in combination with initial intravenous dose titration by patient-controlled analgesia. Lehmann, KA; Zech, DF, 1995)	0.29
" The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined."	( Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H. Collins, JG; Harada, Y; Kishikawa, K; Kitahata, LM; Nishioka, K, 1995)	0.75
"The authors compare the efficacies of trimecaine (8 mg/kg), lidocaine (8 mg/kg), azacaine (2 and 3 mg/kg) alone and in combination with morphine (1."	( [A comparative evaluation of the effects of local anesthetics combined with morphine and administered epidurally]. Cherniakova, IV; Kiselevich, VE; Korinenko, AN; Osipov, SA, )	0.56
"Effects of the kappa opioid agonists, spiradoline (U62,066), enadoline (CI-977) and U69,593, were examined alone and in combination with the opioid antagonists quadazocine and beta-funaltrexamine in squirrel monkeys that responded under a schedule of shock titration."	( Antinociceptive and response rate-altering effects of kappa opioid agonists, spiradoline, enadoline and U69,593, alone and in combination with opioid antagonists in squirrel monkeys. Dykstra, LA; Pitts, RC, 1994)	0.29
" In a prospective study 54 patients undergoing a radical gynaecological operation were allocated to either neuroleptanaesthesia type II or epidural morphine analgesia combined with slight neuroleptanaesthesia."	( [A profound stress reaction during epidural opiate analgesia in combination with weak neuroleptanalgesia in comparison with neuroleptanesthesia Type II alone]. Krug, G, 1993)	0.49
"In a randomized double-blind study, the use of continuous epidural lidocaine during surgery combined with preoperative epidural morphine was compared with that of preoperative epidural morphine alone for postoperative analgesia in 20 patients undergoing hepatectomy."	( [Intraoperative continuous epidural lidocaine combined with preoperative administration of epidural morphine for post-hepatectomy pain relief]. Asada, A; Fujii, T; Terai, T; Yabe, M; Yukioka, H, 1997)	0.72
" The purpose of this study was to determine the effect of epidural bupivacaine combined with morphine on extubation time, postoperative analgesia, respiration, and hemodynamics in patients undergoing esophagectomy."	( Administration of epidural bupivacaine combined with epidural morphine after esophageal surgery. Fujimori, M; Terai, T; Yukioka, H, 1997)	0.76
"Continuous administration of epidural bupivacaine combined with morphine resulted in good analgesia without any respiratory or hemodynamic depression in patients who had undergone esophagectomy, and early extubation is related to the efficacy of continuous epidural administration of bupivacaine."	( Administration of epidural bupivacaine combined with epidural morphine after esophageal surgery. Fujimori, M; Terai, T; Yukioka, H, 1997)	0.78
" We evaluated the quality of analgesia and the incidence of side effects with smaller doses of intrathecal morphine combined with intramuscular (i."	( Small doses of intrathecal morphine combined with systemic diclofenac for postoperative pain control after cesarean delivery. Amaro, AR; Cappelli, EL; Cardoso, MM; Carvalho, JC; Prado, AA, 1998)	0.81
" The purpose of this study was to define HP 228's effects, alone and in combination with morphine, on resting ventilation and the ventilatory response to hypoxia and hypercarbia."	( The respiratory effects of the cytokine regulating agent HP 228 alone and in combination with morphine in human volunteers. Chaplan, SR; Girten, BE; Powell, FL; Weinger, MB, 1998)	0.74
"Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery."	( A double-blinded evaluation of propacetamol versus ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery. Agrò, F; Aloe, L; Ballabio, M; De Cillis, P; De Nicola, A; Giunta, F; Ischia, S; Marinangeli, F; Stefanini, S; Varrassi, G, 1999)	0.75
" combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery."	( Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery. Brennum, J; Dahl, JB; Hansen, TM; Ilkjaer, S; Nikolajsen, L; Wernberg, M, 1998)	0.77
"We report the analgesic and adverse effects of intrathecally administered hyperbaric neostigmine, alone or combined with morphine, in two patients suffering from severe lower limb ischaemic pain (group 1), five patients undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic surgery (group 3) under spinal anaesthesia."	( Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or combined with morphine in patients submitted to spinal anaesthesia: pilot studies. Garcia, LV; Klamt, JG; Prado, WA, 1999)	0.72
"The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with a low dose of bupivacaine were evaluated in 205 patients after upper abdominal surgery."	( [Postoperative epidural analgesia after upper abdominal surgery: the effects of low concentrations of bupivacaine combined with a low dose of opioid]. Kohno, K; Kosaka, Y; Shiihara, K, 1999)	0.52
"Epidural analgesia with lidocaine (trimecaine) in combination with the minimum morphine doses is an effective method for regional pain relief in children."	( [Postoperative epidural analgesia using local anesthetics in combination with morphine in children]. Agzamkhodzhiaev, TS; Satvaldieva, IA, )	0.59
"75% in combination with general inhaled anesthesia without opioids."	( A comparison of the analgesic efficacy of 0.25% levobupivacaine combined with 0.005% morphine, 0.25% levobupivacaine alone, or 0.005% morphine alone for the management of postoperative pain in patients undergoing major abdominal surgery. Crews, JC; Denson, DD; Hord, AH; Schatzman, C, 1999)	0.53
"Pre-incisional epidural K+M+B treatment combined with continuous epidural anaesthesia and general anaesthesia provides an ideal pre-emptive analgesic therapy, exhibiting better postoperative pain relief than general anaesthesia and post-incisional K+M+B treatment."	( Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery. Ho, ST; Lee, MM; Tao, PL; Wong, CS; Wu, CT; Yeh, CC; Yu, JC, 2000)	0.59
"The purpose of this cardiac fast-track study was to evaluate the use of remifentanil (R) combined with intrathecal (IT) morphine as an alternative to sufentanil (S) during desflurane anesthesia with respect to postoperative pain control."	( Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal morphine as an alternative to sufentanil during desflurane anesthesia. Bossard, R; Chi, L; Douning, LK; Latham, P; Morse, L; Shi, C; White, PF; Zarate, E, 2000)	0.74
"As part of a cardiac fast-tracking program involving desflurane anesthesia, the use of intrathecal morphine in combination with a remifentanil infusion provided improved postoperative pain control, compared with IV sufentanil alone."	( Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal morphine as an alternative to sufentanil during desflurane anesthesia. Bossard, R; Chi, L; Douning, LK; Latham, P; Morse, L; Shi, C; White, PF; Zarate, E, 2000)	0.75
"Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively."	( Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery. Kumar, L; Pawar, DK; Subramaniam, B; Subramaniam, K, 2001)	0.76
" These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision."	( Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect. Pawar, DK; Sennaraj, B; Subramaniam, B; Subramaniam, K, 2001)	0.77
"This study evaluates the efficacy and side effects of a low dose of epidural morphine combined with clonidine for postoperative pain relief after lumbar disc surgery."	( Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery. Bonhomme, V; Brichant, JF; Dewandre, PY; Doll, A; Ghassempour, K; Hans, P, 2002)	0.82
" Epidural catheters were inserted at T8-T9 (upper abdominal surgery) or T9-T11 (lower abdominal surgery) and ropivacaine 0,5% 7-9 ml (upper abdominal surgery) or 10-12 ml (lower abdominal surgery) combined with sufentanil 30 mcg (group S, n=30) or with morphine 2 mg (group M, n=30) was injected."	( [Sufentanil vs morphine combined with ropivacaine for thoracic epidural analgesia in major abdominal surgery]. Borghi, B; Clara, ME; De Paolis, P; Gianferrari, P; Marzullo, A; Montone, N; Voltolina, M, 2001)	0.84
"Continuous administration of epidural ropivacaine combined with sufentanil or with morphine resulted in good analgesia."	( [Sufentanil vs morphine combined with ropivacaine for thoracic epidural analgesia in major abdominal surgery]. Borghi, B; Clara, ME; De Paolis, P; Gianferrari, P; Marzullo, A; Montone, N; Voltolina, M, 2001)	0.89
" Few data are available concerning dose requirements of epidural ROPI when combined with morphine."	( A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery. Joris, JL; Lahaye-Goffart, B; Lamy, ML; Ledoux, D; Senard, M; Toussaint, PJ, 2002)	0.77
"The present study examined the effects of SNC80 alone and in combination with the mu opioid agonists, morphine, butorphanol, and buprenorphine to determine whether SNC80 would enhance their antinociceptive effects."	( Antinociceptive effects of the selective delta opioid agonist SNC80 alone and in combination with mu opioids in the squirrel monkey titration procedure. Allen, RM; Dykstra, LA; Granger, AL; Rice, KC; Zhang, X, 2002)	0.53
"Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column."	( Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. Armstrong, SC; Cozza, KL, )	0.67
"We investigated the duration of labor analgesia produced by a small dose of spinal bupivacaine/fentanyl alone or in combination with a small dose of morphine."	( Small dose bupivacaine-fentanyl spinal analgesia combined with morphine for labor. Hess, PE; Pratt, SD; Snowman, C; Vasudevan, A, 2003)	0.76
"We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery."	( Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery. Karaman, H; Kararmaz, A; Kaya, S; Ozyilmaz, MA; Turhanoglu, S, 2003)	0.52
" We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery."	( Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery. Karaman, H; Kararmaz, A; Kaya, S; Ozyilmaz, MA; Turhanoglu, S, 2003)	0.52
"Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column."	( Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II. Armstrong, SC; Cozza, KL, )	0.4
" In this study, we compared the efficacy, dose requirements, side effects, and motor block observed with epidural levobupivacaine and ropivacaine when given in combination with small-dose morphine for 60 h after major abdominal surgery."	( Epidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery. Geortay, MN; Honoré, PD; Jacquemin, MJ; Joris, JL; Kaba, A; Lamy, ML; Maquoi, LM; Senard, M, 2004)	0.75
"1%) of epidural levobupivacaine and ropivacaine combined with morphine (0."	( Epidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery. Geortay, MN; Honoré, PD; Jacquemin, MJ; Joris, JL; Kaba, A; Lamy, ML; Maquoi, LM; Senard, M, 2004)	0.8
"A competitive immunoassay for detecting morphine in bio-samples was established by capillary zone electrophoresis combined with laser-induced fluorescence detection (CZE-LIF)."	( Determination of morphine by capillary zone electrophoresis immunoassay combined with laser-induced fluorescence detection. Chang, WB; Mi, JQ; Zhang, XX, 2004)	0.93
"Dexmedetomidine in combination with morphine PCA provided better analgesia for ESWL and was associated with higher patients' and urologist's satisfaction when compared with a tramadol/midazolam PCA combination."	( Dexmedetomidine in combination with morphine PCA provides superior analgesia for shockwave lithotripsy. Alhashemi, JA; Kaki, AM, 2004)	0.87
"To study the intrinsic parameters of P-glycoprotein (P-gp) transport and drug-drug interactions at the blood-brain barrier (BBB), as few quantitative in vivo data are available."	( In situ transport of vinblastine and selected P-glycoprotein substrates: implications for drug-drug interactions at the mouse blood-brain barrier. Cisternino, S; Debray, M; Rousselle, C; Scherrmann, JM, 2004)	0.32
" Drug-drug interactions were examined using vinblastine and compounds that bind to P-gp sites (verapamil, progesterone, PSC833) other than the vinblastine site to take into account the multispecific drug P-gp recognition."	( In situ transport of vinblastine and selected P-glycoprotein substrates: implications for drug-drug interactions at the mouse blood-brain barrier. Cisternino, S; Debray, M; Rousselle, C; Scherrmann, JM, 2004)	0.32
" In situ perfusion of mdr1a(-/-) and wild-type mouse brains could be used to predict drug-drug interactions for P-gp at the mouse BBB."	( In situ transport of vinblastine and selected P-glycoprotein substrates: implications for drug-drug interactions at the mouse blood-brain barrier. Cisternino, S; Debray, M; Rousselle, C; Scherrmann, JM, 2004)	0.32
"This study was performed to evaluate the effects of cryoanalgesia combined with thoracic epidural analgesia on pain and respiratory complications in patients undergoing thoracotomy."	( The effects of cryoanalgesia combined with thoracic epidural analgesia in patients undergoing thoracotomy. Cho, CH; Kim, YC; Yang, MK, 2004)	0.32
" Use of morphine and butorphanol in combination with alpha2 agonists should be further investigated to assess their analgesic effects."	( Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies. Brearley, JC; Corletto, F; Raisis, AA, 2005)	1.12
"We compared pain intensity and morphine consumption in two postoperative treatment groups: One group received continuous physostigmine infusion combined with morphine-based patient-controlled analgesia (PCA), and the other received PCA alone."	( Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period. Beilin, B; Bessler, H; Papismedov, L; Shavit, Y; Weinstock, M, 2005)	0.88
"Continuous infusion of physostigmine combined with morphine-based PCA in the postoperative period significantly reduced opiate consumption, and enhanced the analgesic response."	( Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period. Beilin, B; Bessler, H; Papismedov, L; Shavit, Y; Weinstock, M, 2005)	0.85
"Physostigmine combined with morphine in the postoperative period reduced morphine consumption, enhanced analgesia, and attenuated production of the proinflammatory cytokine, IL-1beta."	( Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period. Beilin, B; Bessler, H; Papismedov, L; Shavit, Y; Weinstock, M, 2005)	0.89
"To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy."	( Analgesic effects of epidurally administered levogyral ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. Acosta, AD; Bopp, S; Correa-Natalini, C; Gomar, C; Polydoro, A; Sala-Blanch, X, 2005)	0.75
" In the current paper, this new extraction technique was combined with liquid chromatography-mass spectrometry (LC-MS) for the first time."	( Liquid-phase microextraction based on carrier mediated transport combined with liquid chromatography-mass spectrometry. New concept for the determination of polar drugs in a single drop of human plasma. Anthonsen, HS; Ho, TS; Pedersen-Bjergaard, S; Rasmussen, KE; Reubsaet, JL, 2005)	0.33
" The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids."	( Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction. Legeby, M; Olofsson, C; Sandelin, K; Wickman, M, 2005)	0.58
" The latter finding demonstrates that administration-time-dependent differences in drug-drug interactions need to be considered in both experimental designs and clinical settings."	( Temporal variation in drug interaction between lithium and morphine-induced analgesia. Bora, N; Demirel, O; Karakucuk, EH; Yamanoglu, T; Zengil, H, 2006)	0.58
"To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe (NUR) combined with opioid analgesics in managing cancer pain."	( Clinical research on nourishing yin and unblocking meridians recipe combined with opioid analgesics in cancer pain management. Deng, QH; Ma, SL; Pan, XC; Tang, ZZ; Xie, GR; Xu, S; Zhang, M; Zhang, T, 2006)	0.33
" Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups."	( Clinical research on nourishing yin and unblocking meridians recipe combined with opioid analgesics in cancer pain management. Deng, QH; Ma, SL; Pan, XC; Tang, ZZ; Xie, GR; Xu, S; Zhang, M; Zhang, T, 2006)	0.33
"NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone."	( Clinical research on nourishing yin and unblocking meridians recipe combined with opioid analgesics in cancer pain management. Deng, QH; Ma, SL; Pan, XC; Tang, ZZ; Xie, GR; Xu, S; Zhang, M; Zhang, T, 2006)	0.33
") administration of D-serine, a selective agonist for the glycine site of the NMDA receptors, alone or in combination with morphine using the tail-flick test."	( Activation of supraspinal NMDA receptors by both D-serine alone or in combination with morphine leads to the potentiation of antinociception in tail-flick test of rats. Akahori, K; Hashimoto, A; Ito, K; Jin, XL; Kobayashi, H; Maeda, M; Matsuda, M; Oka, T; Suzuki, T; Takahashi, S; Yoshikawa, M, 2007)	0.77
" If patients receive morphine and these drugs simultaneously, the drug-drug interaction may change the levels of morphine and these glucuronides, resulting in altered analgesic efficacy and the risk of side effects."	( Morphine glucuronosyltransferase activity in human liver microsomes is inhibited by a variety of drugs that are co-administered with morphine. Hara, Y; Miyamoto, K; Nakajima, M; Yokoi, T, 2007)	2.1
"Although caudal morphine may result in more sustained initial analgesia, caudal clonidine combined with nurse-controlled analgesia appears to provide comparable analgesia with fewer side effects."	( A comparison of single-dose caudal clonidine, morphine, or hydromorphone combined with ropivacaine in pediatric patients undergoing ureteral reimplantation. Carvallo, D; Johnson, JL; Mazurek, MS; Presson, RG; Vetter, TR, 2007)	0.94
"The present study examined the interactive effects of morphine in combination with metabotropic glutamate (mGlu) receptor antagonists on schedule-controlled responding and thermal nociception."	( Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception. Dykstra, LA; Fischer, BD; Picker, MJ; Zimmerman, EI, 2008)	2.04
"To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy."	( Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs. Hatschbach, E; Luna, SP; Marucio, RL; Minto, BW; Neto, FJ, 2008)	0.78
" We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy."	( Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial. Dahl, JB; Dierking, G; Fomsgaard, JS; Hilsted, KL; Lech, K; Lose, G; Mathiesen, O; Rasmussen, ML, 2009)	0.35
"To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs."	( Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs. Assis, HM; Campagnol, D; Junior, AR; Monteiro, ER; Quitzan, JG, 2009)	0.91
" Continuous basal infusion of drugs combined with standard patient-controlled analgesia (PCA) is considered to be an effective means of postoperative acute pain management."	( Continuous infusion of butorphanol combined with intravenous morphine patient-controlled analgesia after total abdominal hysterectomy: a randomized, double-blind controlled trial. Guo, X; Liu, Y; Shen, X; Wang, F; Xu, S, 2009)	0.59
"Basal infusion of butorphanol combined with intravenous morphine PCA in patients undergoing abdominal hysterectomy shows effective analgesia with sedation and fewer side effects."	( Continuous infusion of butorphanol combined with intravenous morphine patient-controlled analgesia after total abdominal hysterectomy: a randomized, double-blind controlled trial. Guo, X; Liu, Y; Shen, X; Wang, F; Xu, S, 2009)	0.84
" This study compared, in donor right hepatectomy, the efficacy and safety of preoperative intrathecal morphine (ITM) combined with intravenous patient-controlled analgesia (IV-PCA) with IV-PCA alone."	( Intrathecal morphine combined with intravenous patient-controlled analgesia is an effective and safe method for immediate postoperative pain control in live liver donors. Ahn, HJ; Cho, HS; Choi, SJ; Gwak, MS; Hahm, TS; Joh, JW; Kim, GS; Kim, JA; Kim, KM; Ko, JS, 2009)	0.95
" We performed a meta-analysis to obtain more detailed information on the frequency of side-effects in patients receiving intrathecal morphine in combination with spinal anaesthesia compared with placebo treated patients."	( Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: a meta-analysis. Gehling, M; Tryba, M, 2009)	0.83
"To evaluate the effects of patient-controlled analgesia (PCA) with small dose ketamine combined with morphine on analgesia and influence thereof on the plasma beta-endorphin (EP) level in the patients after radical operation for esophageal carcinoma."	( [Effects of patient-controlled analgesia with small dose ketamine combined with morphine and the influence thereof on plasma beta-endorphin level in patients after radical operation for esophageal carcinoma]. Feng, J; Huang, XM; Li, H; Ma, LY; Wu, YQ; Xiong, JC; Xu, ZM; Zhang, DT, 2009)	0.8
"The aim of this work was to investigate the effect on antioxidant potential of some commonly used drugs (morphine, tramadol, bromocriptine, haloperidol and azithromycin) on immobilization stress (IS) combined with cold restraint stress (CRS) in the rat."	( Antioxidant effects of some drugs on immobilization stress combined with cold restraint stress. Janicijevic-Hudomal, S; Kaurinovic, B; Popovic, M; Rasic, J; Trivic, S; Vojnović, M, 2009)	0.57
"This double blind, randomized, controlled trial investigated whether a single preoperative intravenous (iv) dose of tramadol (100 mg) given 30 min before abdominal hysterectomy resulted in improved analgesic efficacy, reduced postoperative morphine patient-controlled analgesia (PCA) use and reduced side effects when combined with a postoperative small-dose tramadol infusion."	( Preoperative tramadol combined with postoperative small-dose tramadol infusion after total abdominal hysterectomy: a double-blind, randomized, controlled trial. Liu, Y; Shen, X; Wang, F; Xu, S, )	0.31
"To compare the efficacy of 2 preemptive analgesics: continuous subcutaneous morphine alone (SC) and continuous subcutaneous morphine combined with single intrathecal injection of morphine (SI)."	( A case-control study of preemptive analgesia for postoperative pain in patients undergoing posterior lumbar interbody fusion: continuous subcutaneous morphine alone and combined with intrathecal injection. Hirano, K; Ito, K; Kato, F; Machino, M; Nakashima, H; Tauchi, R; Yukawa, Y, 2010)	0.79
" Our aim was to evaluate feasibility, safety, and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion (CSI) for cancer pain in a prospective observational open-label pilot study."	( Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain. Cruto, M; Debernardi, F; Massucco, P; Moselli, NM; Savojardo, M, 2010)	0.59
"Ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain."	( Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain. Cruto, M; Debernardi, F; Massucco, P; Moselli, NM; Savojardo, M, 2010)	0.59
"The objective of this study was to determine the effects of a constant rate of infusion of lidocaine and ketamine in combination with either morphine or fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) during ovariohysterectomy in dogs."	( Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl. Aguado, D; Benito, J; Gómez de Segura, IA, 2011)	0.77
"to examine effectiveness and overall opiate consumption between high-sensory transcutaneous electrical nerve stimulation (Hi-TENS) combined with patient-controlled analgesia with morphine and patient-controlled analgesia with morphine alone following elective (e."	( Hi-TENS combined with PCA-morphine as post caesarean pain relief. Binder, P; Gustafsson, A; Nissen, E; Uvnäs-Moberg, K, 2011)	0.86
"participants were randomly assigned and connected to patient-controlled analgesia with morphine alone or in combination with Hi-TENS apparatus."	( Hi-TENS combined with PCA-morphine as post caesarean pain relief. Binder, P; Gustafsson, A; Nissen, E; Uvnäs-Moberg, K, 2011)	0.89
" A presumed benefit of this treatment combination is that the mother is more alert and better able to interact with her newborn during the first hours after birth without drowsiness due to large doses of opiates."	( Hi-TENS combined with PCA-morphine as post caesarean pain relief. Binder, P; Gustafsson, A; Nissen, E; Uvnäs-Moberg, K, 2011)	0.67
"Our prospective, randomized, double-blind study aimed to detect the effect of intrathecal levobupivacaine combined with fentanyl or morphine on the postoperative analgesia in patients undergoing cesarean section."	( [Assessment of the effect of intrathecal levobupivacaine combined with fentanyl or morphine on postoperative analgesia in patients undergoing cesarean section]. Acar, P; Akyol, O; Ozyuvacı, E; Toprak, N; Vatansever, S, 2010)	0.79
"we compared the clinical efficacy and safety between a new injectable cyclooxygenase-2 selective inhibitor, parecoxib, and an old nonselective, ketorolac combined with morphine in patient-controlled analgesia (PCA) for management of post-cesarean delivery pain."	( Comparison of the efficacy of parecoxib versus ketorolac combined with morphine on patient-controlled analgesia for post-cesarean delivery pain management. Cheu, NW; Chuang, FH; Liao, CH; Tan, TD; Wang, YR; Watts, MP; Wong, JO, 2010)	0.79
" Morphine was basically used in PCA manner during the 3-day study course; and in Group K patients received an intravenous loading bolus of 30mg ketorolac post-operatively and then 90mg ketorolac combined with morphine in PCA fashion throughout the study course."	( Comparison of the efficacy of parecoxib versus ketorolac combined with morphine on patient-controlled analgesia for post-cesarean delivery pain management. Cheu, NW; Chuang, FH; Liao, CH; Tan, TD; Wang, YR; Watts, MP; Wong, JO, 2010)	1.5
" The nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation provides a rapid, efficient and accurate platform for the quantification of small molecules in urine samples."	( Nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation for quantification of small molecules. Chen, YJ; Fuh, MR; Ho, YC; Lin, CC; Lu, YW; Tseng, MC, 2011)	0.37
"The present study examined the effects of the mGluR1 antagonist JNJ16259685 (JNJ) and the mGluR5 antagonist 2-methyl-6-phenylethynylpyridine (MPEP) alone and in combination with morphine in two acute pain models (hotplate, warm water tail-withdrawal), and a persistent, inflammatory pain model (capsaicin)."	( Metabotropic glutamate antagonists alone and in combination with morphine: comparison across two models of acute pain and a model of persistent, inflammatory pain. Daugherty, D; Dykstra, LA; Henry, FE; Miller, LL; Picker, MJ, 2011)	0.8
" Additional experiments examined these compounds in combination with morphine."	( Effects of alterations in cannabinoid signaling, alone and in combination with morphine, on pain-elicited and pain-suppressed behavior in mice. Dykstra, LA; Miller, LL; Picker, MJ; Schmidt, KT; Umberger, MD, 2012)	0.84
" The STR was mimicked in mice treated with BD 1047 (a putative σ(1) receptor antagonist), but not SM-21, a putative σ(2) receptor antagonist, in combination with METH."	( Straub tail reaction in mice treated with σ(1) receptor antagonist in combination with methamphetamine. Hall, FS; Kitanaka, J; Kitanaka, N; Nishiyama, N; Takemura, M; Tanaka, K; Uhl, GR, 2012)	0.38
"This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats."	( Rewarding effects of ethanol combined with low doses of morphine through dopamine D1 receptors. Ise, Y; Katayama, S; Mori, T; Nagase, H; Suzuki, T, 2013)	0.87
" This study was designed to compare the efficacy of intrathecal (IT) morphine alone, or in combination with bupivacaine and fentanyl, as part of a combined spinal-epidural (CSE) analgesia, in patients undergoing elective total gastrectomy."	( Comparison of analgesic effect of intrathecal morphine alone or in combination with bupivacaine and fentanyl in patients undergoing total gastrectomy: a prospective randomized, double blind clinical trial. Gerić, V; Ivanoviić, N; Karanikolas, M; Randjelović, T; Rasković, J; Slavković, Z; Stamenković, DM; Tomić, A; Veljović, M, 2013)	0.88
"25), although this enhancement was not observed when morphine was combined with 17 mg/kg pregabalin."	( Assessment of the antinociceptive effects of pregabalin alone or in combination with morphine during acetic acid-induced writhing in mice. Keyhanfar, F; Shamsi Meymandi, M, 2013)	0.86
"In this study, the MCF-7 breast cancer cells were used to determine the antitumor effects of the 5-FU in combination with morphine."	( Morphine improved the antitumor effects on MCF-7 cells in combination with 5-Fluorouracil. Ge, ZH; Hao, CL; Sun, LX; Sun, Y; Wang, ZX; Yang, N; Yu, TL, 2014)	2.05
"It was shown that in MCF-7 cells, the proliferation was inhibited, the apoptosis was promoted, the Bcl-2 expression was suppressed and the Bax expression was promoted by both 5-FU alone and morphine alone, while the superior effects were achieved in combination with the two drugs."	( Morphine improved the antitumor effects on MCF-7 cells in combination with 5-Fluorouracil. Ge, ZH; Hao, CL; Sun, LX; Sun, Y; Wang, ZX; Yang, N; Yu, TL, 2014)	2.04
" Morphine at 1 or 2 mg/kg combined with medetomidine and alfaxalone in rabbits produced a suitable level of anaesthesia, although profound cardiorespiratory depression was found."	( Cardiorespiratory, anaesthetic and recovery effects of morphine combined with medetomidine and alfaxalone in rabbits. Del Mar Granados, M; Fernández-Sarmiento, A; Gómez-Villamandos, RJ; López Villalba, I; Manuel Domínguez, J; Morgaz, J; Muñoz-Rascón, P; Navarrete-Calvo, R, 2014)	1.56
"The present study concluded that, low-dose ITM combination with SSFNB provided good pain relief with low side effects and reduced morphine consumption during the first 24 hours post TKA."	( Effects of single shot femoral nerve block combined with intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after total knee arthroplasty. Chanthong, P; Intiyanaravut, T; Kunopart, M; Pethuahong, C; Thongpolswat, N, 2014)	0.84
"To evaluate the analgesic effect of pregabalin combined with intrathecal sufentanil infusion for the treatment of breakthrough pain in patients with bone metastases."	( [Pregabalin combined with intrathecal sufentanil infusion for breakthrough pain in patients with bone metastases]. Cao, Q; Gu, S; Huang, D; Wu, L; Xu, H, 2014)	0.4
"A total of 60 breakthrough pain patients with bone metastases were randomly divided to 3 groups: group A (pregabalin combined with intrathecal sufentanil infusion group, n=20), group B (placebo combined with intrathecal sufentanil infusion group, n=20) and group C (oral morphine sulfate controlled-release tablet group, n=20)."	( [Pregabalin combined with intrathecal sufentanil infusion for breakthrough pain in patients with bone metastases]. Cao, Q; Gu, S; Huang, D; Wu, L; Xu, H, 2014)	0.58
"Pregabalin combined with intrathecal sufentanil infusion can effectively relieve breakthrough pain in patients with bone metastases."	( [Pregabalin combined with intrathecal sufentanil infusion for breakthrough pain in patients with bone metastases]. Cao, Q; Gu, S; Huang, D; Wu, L; Xu, H, 2014)	0.4
" We hypothesized that ITM combined with IVPCA is as effective as patient controlled thoracic epidural analgesia (PCTEA) with respect to postoperative pain control after conventional open gastrectomy."	( Efficacy of intrathecal morphine combined with intravenous analgesia versus thoracic epidural analgesia after gastrectomy. Choi, SH; Kil, HK; Koo, BN; Lee, JH; Noh, SH; Park, JH, 2014)	0.71
"Sixty-four patients undergoing conventional open gastrectomy due to gastric cancer were randomly allocated into the intrathecal morphine combined with intravenous patient-controlled analgesia (IT) group or patient-controlled thoracic epidural analgesia (EP) group."	( Efficacy of intrathecal morphine combined with intravenous analgesia versus thoracic epidural analgesia after gastrectomy. Choi, SH; Kil, HK; Koo, BN; Lee, JH; Noh, SH; Park, JH, 2014)	0.91
"To evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs."	( Cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs. Cardoso, CG; da Silva, TH; de Mattos-Junior, E; Marques, DR, 2014)	0.82
"To compare the antinociceptive effects of magnesium sulphate (MgSO(4)) when administered epidurally alone and in combination with morphine."	( Antinociceptive effects of epidural magnesium sulphate alone and in combination with morphine in dogs. Bahrenberg, A; Dzikiti, BT; Fosgate, GT; Rioja, E; Stegmann, FG; Tacke, SP, 2015)	0.85
"1 mg kg(-1)) alone (Mo), MgSO(4) in combination with morphine (Mm), and sterile water (0."	( Antinociceptive effects of epidural magnesium sulphate alone and in combination with morphine in dogs. Bahrenberg, A; Dzikiti, BT; Fosgate, GT; Rioja, E; Stegmann, FG; Tacke, SP, 2015)	0.89
"When administered epidurally, morphine alone or in combination with neostigmine provided effective postoperative analgesia in most dogs after orthopedic surgery, whereas neostigmine alone did not."	( Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in dogs undergoing orthopedic surgery of the pelvic limbs. Fantoni, DT; Marucio, RL; Monteiro, ER; Moroz, LR, 2014)	0.91
" The authors aimed to investigate the efficacy of low concentrations of dezocine in combination with morphine for postoperative pain."	( Low Concentration of Dezocine in Combination With Morphine Enhance the Postoperative Analgesia for Thoracotomy. Dong, YP; Sun, L; Wu, L, 2015)	0.89
"The morphine group (Group M) received morphine (1 mg/mL) alone for patient-controlled analgesia (PCA); the morphine+dezocine 1 group (Group MD1) received morphine (1 mg/mL) combined with dezocine (0."	( Low Concentration of Dezocine in Combination With Morphine Enhance the Postoperative Analgesia for Thoracotomy. Dong, YP; Sun, L; Wu, L, 2015)	1.23
"A total of 53 patients with American Society of Anesthesiologists (ASA) I-II status randomly received general anesthesia (G group, n = 27) or general anesthesia combined with epidural anesthesia (E group, n = 26) for surgical tumor resection."	( General anesthesia combined with epidural anesthesia ameliorates the effect of fast-track surgery by mitigating immunosuppression and facilitating intestinal functional recovery in colon cancer patients. Chen, WK; Miao, CH; Ren, L; Wei, Y; Xu, JM; Zhu, DX, 2015)	0.42
"General anesthesia combined with epidural anesthesia plays an important role in fast-track surgery, mitigating the surgical stress-related impairment of anti-tumor immune responses and hastening the recovery of intestinal function."	( General anesthesia combined with epidural anesthesia ameliorates the effect of fast-track surgery by mitigating immunosuppression and facilitating intestinal functional recovery in colon cancer patients. Chen, WK; Miao, CH; Ren, L; Wei, Y; Xu, JM; Zhu, DX, 2015)	0.42
"This study evaluated the use of the injectable anesthetic, alphaxalone, as a single agent and in combination with ketamine, xylazine, and morphine in the Chilean rose tarantula, Grammostola rosea."	( The use of injectable alphaxalone as a single agent and in combination with ketamine, xylazine, and morphine in the Chilean rose tarantula, Grammostola rosea. Gjeltema, J; Posner, LP; Stoskopf, M, 2014)	0.82
"To investigate cardiorespiratory effects and serum concentration of ropivacaine combined with morphine at different doses."	( Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg(-1) in bitches undergoing epidural anesthesia. Albuquerque, VB; Araújo, MA; Arruda, AM; Ferreira, GT; Fonseca, MW; Oliva, VN; ShiChen, L, 2015)	0.91
"To evaluate the cardiopulmonary and sedative effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep."	( Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. Auckburally, A; Borges, LP; Cerejo, SA; de Carvalho, LL; de Mattos-Junior, E; Nishimura, LT; Villela, IO, 2016)	0.87
" Each drug combination was mixed in the syringe and injected intravenously."	( Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. Auckburally, A; Borges, LP; Cerejo, SA; de Carvalho, LL; de Mattos-Junior, E; Nishimura, LT; Villela, IO, 2016)	0.66
"Objectives The aim of the study was to evaluate the effectiveness of epidural lidocaine in combination with either methadone or morphine for postoperative analgesia in cats undergoing ovariohysterectomy."	( Postoperative pain control in cats: clinical trials with pre-emptive lidocaine epidural co-administered with morphine or methadone. de Andrade Bicudo, N; de Assis, KT; DeRossi, R; Hermeto, LC; Jardim, PHA, 2016)	0.85
"To compare sedative and analgesic properties of buprenorphine or morphine for standing procedures combined with a detomidine continuous rate infusion (CRI)."	( Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses. Love, EJ; MacFarlane, PD; Murrell, JC; Potter, JJ; Taylor, PM; Tremaine, H, 2016)	0.89
" The aim of the study was to determine the effects of constant-rate infusion of lidocaine and ketamine combined with either morphine or fentanyl on the MAC of sevoflurane in pigs."	( Effect of Lidocaine-Ketamine Infusions Combined with Morphine or Fentanyl in Sevoflurane-Anesthetized Pigs. Canfrán, S; Gómez de Segura, IA; Largo, C; Re, M, 2016)	0.89
"To observe analgesic and sedative effect of acupuncture combined with medicine (ACM) on patients undergiong cardiac surgery."	( [Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery]. Cao, WZ; Xu, SA; Xu, XQ; Yu, HJ, 2016)	0.43
" Patients in group A were subjected to analgesia and sedation by injecting dexmedetomidine, while patients in group B were subjected to analgesia and sedation by electro-acupuncture [EA, Shenting (GV24); Yintang (EX-HN3)] combined with injection of dexmedetomidine."	( [Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery]. Cao, WZ; Xu, SA; Xu, XQ; Yu, HJ, 2016)	0.43
" We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery."	( Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial. Alshaeri, T; Amdur, RL; Berger, JS; Gonzalez, A; Hopkins, A; Jeon, D; Smiley, R; Wang, S, 2016)	0.94
"Because nefopam's morphine-sparing is debated when combined with paracetamol, this study aimed to assess pain relief by IV nefopam in combination with paracetamol after major abdominal surgery."	( Opioid-sparing effect of nefopam in combination with paracetamol after major abdominal surgery: a randomized double-blind study. Alonso, S; Casano, F; Cuvillon, P; Demattei, C; L'hermite, J; Lefrant, JY; Muller, L; Ripart, J; Zoric, L, 2017)	0.79
"This prospective randomized study suggested that nefopam in combination with paracetamol has no benefit after open abdominal surgery."	( Opioid-sparing effect of nefopam in combination with paracetamol after major abdominal surgery: a randomized double-blind study. Alonso, S; Casano, F; Cuvillon, P; Demattei, C; L'hermite, J; Lefrant, JY; Muller, L; Ripart, J; Zoric, L, 2017)	0.46
" Hyperbaric bupivacaine 3 mg combined with 50 mcg of intradural morphine hydrochloride (BUP-MOR group) was compared with 5 mg hyperbaric bupivacaine (BUP group)."	( Intraspinal administration of morphine hydrochloride combined with low doses of bupivacaine in hemorrhoidectomy: a clinical randomized trial. de Abajo Iglesias, FJ; Rodríguez-Miguel, A; Ruiz-Castro, M; San José Santos, M, 2017)	0.98
" Solutions containing mixtures of methadone combined with acepromazine, medetomidine or xylazine were stored in syringes at 25°C/60%RH."	( Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes. Lee, DY; Watson, N; Whittem, T, 2017)	0.77
" When in combination with acepromazine or xylazine, methadone also remained chemically stable, but the combination with medetomidine failed stability criteria prior to 6 months."	( Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes. Lee, DY; Watson, N; Whittem, T, 2017)	0.77
"OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of dexmedetomidine combined with commonly administered opioids in dogs."	( Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs. Auckburally, A; de Mattos-Junior, E; Garcia, DO; Honsho, CS; Nishimura, LT; Santilli, J; Vieira, BHB, 2018)	0.48
" The aim of our study was to test the effects of dexmedetomidine in combination with opioids and benzodiazepines compared to benzodiazepine-opioids alone."	( Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial. Benegni, S; Cogo, P; Garisto, C; Pezzella, C; Ricci, Z; Tofani, L, 2018)	0.48
"Low dose of dexmedetomidine in combination with morphine and midazolam was safe in a high-risk cohort of CHD children after cardiac surgery and reduced the onset of withdrawal symptoms."	( Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial. Benegni, S; Cogo, P; Garisto, C; Pezzella, C; Ricci, Z; Tofani, L, 2018)	0.74
"Dexmedetomidine in combination with opioids has been used for postoperative analgesia."	( Dexmedetomidine in combination with morphine improves postoperative analgesia and sleep quality in elderly patients after open abdominal surgery: A pilot randomized control trial. Hu, J; Li, CJ; Li, HJ; Mu, DL; Wang, DX; Wei, XN, 2018)	0.76
" These data suggest a mechanism of medication overuse headache by which migraine medications combined with repeated episodes of pain may amplify the consequences of nociceptor activation and increase the probability of future migraine attacks as well as risk of medication overuse headache."	( Sustained exposure to acute migraine medications combined with repeated noxious stimulation dysregulates descending pain modulatory circuits: Relevance to medication overuse headache. Dodick, DW; Nation, KM; Navratilova, E; Porreca, F, 2019)	0.51
"To study the effect of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal (ICC) in rabbits."	( Effects of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal in rabbits. Li, YH; Luo, H; Yang, H, 2019)	1.06
"Epidural infusions of morphine combined with small-dose naloxone effectively inhibit the gastrointestinal motility of rabbits via the reduction of ICC in the proximal colon of the gastrointestinal tract of rabbits."	( Effects of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal in rabbits. Li, YH; Luo, H; Yang, H, 2019)	1.11
" However, whether ACB combined with LIA has synergistic effect than ACB alone remains unknown."	( Dose adductor canal block combined with local infiltration analgesia has a synergistic effect than adductor canal block alone in total knee arthroplasty: a meta-analysis and systematic review. Cui, W; Guo, W; Ma, J; Zuo, W, 2019)	0.51
" Here, we evaluated the efficacy of single-shot ACB combined with posterior capsular infiltration (PCI) vs multimodal periarticular infiltration analgesia in treating postoperative pain."	( Efficacy of Single-Shot Adductor Canal Block Combined With Posterior Capsular Infiltration on Postoperative Pain and Functional Outcome After Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Study. Kang, P; Li, D; Wang, Q; Yang, Z; Yeersheng, R; Yue, Y, 2019)	0.51
" Patients were randomized into 2 groups, one of which was treated with ACB combined with PCI, and the other with periarticular infiltration analgesia."	( Efficacy of Single-Shot Adductor Canal Block Combined With Posterior Capsular Infiltration on Postoperative Pain and Functional Outcome After Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Study. Kang, P; Li, D; Wang, Q; Yang, Z; Yeersheng, R; Yue, Y, 2019)	0.51
"The ACB combined with PCI can reduce postoperative pain sooner after TKA without affecting postoperative functional recovery and increasing complications."	( Efficacy of Single-Shot Adductor Canal Block Combined With Posterior Capsular Infiltration on Postoperative Pain and Functional Outcome After Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Study. Kang, P; Li, D; Wang, Q; Yang, Z; Yeersheng, R; Yue, Y, 2019)	0.51
"This study evaluated the effects of 3 morphine doses combined with acepromazine, on sedation and physiological parameters in 5 clinically healthy dogs."	( Effects of 3 morphine doses, in combination with acepromazine, on sedation and some physiological parameters in dogs. Campagnol, D; Freire, CD; Monteiro, ER; Nunes, JS; Rabello, TA; Rangel, JPP, 2019)	1.15
"The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia."	( Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane. Chambers, P; Karna, SR; Kongara, K; Singh, P, 2020)	1.12
"" The present studies tested the hypothesis that in evoked pain, certain chemokine receptor antagonists (CRAs), given with a submaximal dose of morphine, would result in enhanced morphine potency."	( Chemokine Receptor Antagonists in Combination with Morphine as a Novel Strategy for Opioid Dose Reduction in Pain Management. Adler, MW; Chen, X; Cowan, A; Eisenstein, TK; Geller, EB; Inan, S; Meissler, JJ; Rawls, SM; Tallarida, CS, 2020)	1.01
" In the cold-water tail flick and formalin tests, significant increases of the antinociceptive effects of morphine were also observed when combined with CRAs."	( Chemokine Receptor Antagonists in Combination with Morphine as a Novel Strategy for Opioid Dose Reduction in Pain Management. Adler, MW; Chen, X; Cowan, A; Eisenstein, TK; Geller, EB; Inan, S; Meissler, JJ; Rawls, SM; Tallarida, CS, 2020)	1.02
" In this paper, a novel strategy for quality assessment of PPCE, systematic quantified fingerprint method (SQFM) combined with quantitative analysis of multi-components by a single marker (QAMS) method, was developed and validated."	( Quality evaluation of powdered poppy capsule extractive by systematic quantified fingerprint method combined with quantitative analysis of multi-components by single marker method. Guo, Y; Sun, G; Wang, Y; Yu, Y, 2020)	0.56
"To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism."	( [Early intervention of bone-nearby acupuncture combined with electroacupuncture on morphine tolerance in bone cancer pain rats and its effect on the expression of HDAC and MOR in dorsal root ganglia]. Cai, YQ; Chen, F; Du, JY; Fang, JF; Fang, JQ; Jiang, B; Liang, Y; Zhong, XM; Zhou, J, 2020)	0.96
"Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia."	( [Early intervention of bone-nearby acupuncture combined with electroacupuncture on morphine tolerance in bone cancer pain rats and its effect on the expression of HDAC and MOR in dorsal root ganglia]. Cai, YQ; Chen, F; Du, JY; Fang, JF; Fang, JQ; Jiang, B; Liang, Y; Zhong, XM; Zhou, J, 2020)	1
" We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone."	( Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome? Andersen, CU; Andersen, FD; Simonsen, U, 2021)	0.83
"This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression."	( Clinical Efficacy of Controlled-Release Morphine Tablets Combined with Celecoxib in Pain Management and the Effects on WNK1 Expression. Dong, J; Li, J; Luan, F; Shang, M; Song, J, 2021)	1.12
"5 mg/kg) combined with lidocaine (2 mg/kg) or lidocaine (2 mg/kg) only (control treatment)."	( Neuraxial administration of morphine combined with lidocaine induces regional antinociception in inland bearded dragons (Pogona vitticeps). Ferreira, TH; Fink, DM; Mans, C, 2021)	0.92
"This study was aimed at exploring the efficacy of morphine combined with mechanical ventilation in the treatment of heart failure with artificial intelligence algorithms."	( Efficacy of Morphine Combined with Mechanical Ventilation in the Treatment of Heart Failure with Cardiac Magnetic Resonance Imaging under Artificial Intelligence Algorithms. Chen, B; Geng, Z; Han, X; Li, Q; Zhu, X, 2022)	1.35
"The purpose of this study was to evaluate the efficacy of intrathecal morphine (ITM) in combination with bupivacaine as pre-emptive analgesia in patients undergoing posterior lumbar fusion surgery."	( Intrathecal morphine in combination with bupivacaine as pre-emptive analgesia in posterior lumbar fusion surgery: a retrospective cohort study. Balain, B; Dheerendra, S; Ghodke, A; John, J; Kuiper, J; Munigangaiah, S; Ockendon, M; Trivedi, J; Trivedi, R, 2022)	1.33
"ITM in combination with bupivacaine results in a significantly decreased use of perioperative opioids."	( Intrathecal morphine in combination with bupivacaine as pre-emptive analgesia in posterior lumbar fusion surgery: a retrospective cohort study. Balain, B; Dheerendra, S; Ghodke, A; John, J; Kuiper, J; Munigangaiah, S; Ockendon, M; Trivedi, J; Trivedi, R, 2022)	1.1
" The purpose of this study was to evaluate whether ACB combined with a LIA cocktail of ropivacaine, morphine, and betamethasone has superior analgesic effect than LIA for TKA."	( Adductor canal block combined with local infiltration analgesia with morphine and betamethasone show superior analgesic effect than local infiltration analgesia alone for total knee arthroplasty: a prospective randomized controlled trial. Chen, X; Luo, ZY; Wang, HY; Xiao, Q; Yu, QP; Zeng, WN; Zhou, Z, 2022)	1.17
" ACB combined with LIA had significantly lower resting and active VAS pain scores, better ROM, better sleeping quality and higher satisfaction rates than LIA alone within 72 h postoperatively (P < 0."	( Adductor canal block combined with local infiltration analgesia with morphine and betamethasone show superior analgesic effect than local infiltration analgesia alone for total knee arthroplasty: a prospective randomized controlled trial. Chen, X; Luo, ZY; Wang, HY; Xiao, Q; Yu, QP; Zeng, WN; Zhou, Z, 2022)	0.96
"Adductor canal block combined with Local infiltration analgesia provide better early pain control."	( Adductor canal block combined with local infiltration analgesia with morphine and betamethasone show superior analgesic effect than local infiltration analgesia alone for total knee arthroplasty: a prospective randomized controlled trial. Chen, X; Luo, ZY; Wang, HY; Xiao, Q; Yu, QP; Zeng, WN; Zhou, Z, 2022)	0.96
"This retrospective study evaluated the efficacy, opioid consumption, and safety profile of two patient-controlled intravenous analgesia (PCIA) regimens (sufentanil combined with nalbuphine vs sufentanil alone) after cesarean section (CS)."	( Sufentanil Combined with Nalbuphine via Patient-Controlled Intravenous Analgesia After Cesarean Section: A Retrospective Evaluation. Ma, Y; Mu, X; Nie, H; Wang, H; Wang, L; Wang, Y; Zhang, Z; Zheng, Z, 2022)	0.72
"Parturients (n = 1808) received sufentanil combined with nalbuphine (SN group) or sufentanil alone (S group) as PCIA after CS."	( Sufentanil Combined with Nalbuphine via Patient-Controlled Intravenous Analgesia After Cesarean Section: A Retrospective Evaluation. Ma, Y; Mu, X; Nie, H; Wang, H; Wang, L; Wang, Y; Zhang, Z; Zheng, Z, 2022)	0.72
"Compared with sufentanil alone, sufentanil combined with nalbuphine for PCIA provided superior analgesia in parturient women after CS."	( Sufentanil Combined with Nalbuphine via Patient-Controlled Intravenous Analgesia After Cesarean Section: A Retrospective Evaluation. Ma, Y; Mu, X; Nie, H; Wang, H; Wang, L; Wang, Y; Zhang, Z; Zheng, Z, 2022)	0.72
"To investigate the effect of intrathecal morphine, dexmedetomidine, or both in combination with bupivacaine on cellular immunity and cytokine production in cancer surgical patients."	( Immunosuppressive Effect of Intrathecal Morphine, Dexmedetomidine, or Both in Combination with Bupivacaine on Patients Undergoing Major Abdominal Cancer Surgery. Abdelemam, RM; Elmasry, HM; Fares, KM; Kamal, SM; Mansour, S; Mohamed, SA, 2022)	1.25
"Intrathecal dexmedetomidine has the least immunosuppressive effect than morphine and morphine-dexmedetomidine, in combination with bupivacaine."	( Immunosuppressive Effect of Intrathecal Morphine, Dexmedetomidine, or Both in Combination with Bupivacaine on Patients Undergoing Major Abdominal Cancer Surgery. Abdelemam, RM; Elmasry, HM; Fares, KM; Kamal, SM; Mansour, S; Mohamed, SA, 2022)	1.22
"This study examined whether pericapsular nerve group (PENG) block combined with local infiltration analgesia (LIA) could improve pain management and functional recovery after total hip arthroplasty."	( Efficacy of Ultrasound-Guided Pericapsular Nerve Group (PENG) Block Combined With Local Infiltration Analgesia on Postoperative Pain After Total Hip Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Trial. Hu, J; Kang, P; Wang, Q; Yang, J, 2023)	0.91
"All patients were randomly assigned to receive PENG block combined with LIA (PENG group) or sham PENG block and LIA (Sham group)."	( Efficacy of Ultrasound-Guided Pericapsular Nerve Group (PENG) Block Combined With Local Infiltration Analgesia on Postoperative Pain After Total Hip Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Trial. Hu, J; Kang, P; Wang, Q; Yang, J, 2023)	0.91
"PENG block combined with LIA could improve postoperative pain relief, reduce opioid use, and enhance recovery in total hip arthroplasty patients, without weakening the quadriceps muscle strength."	( Efficacy of Ultrasound-Guided Pericapsular Nerve Group (PENG) Block Combined With Local Infiltration Analgesia on Postoperative Pain After Total Hip Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Trial. Hu, J; Kang, P; Wang, Q; Yang, J, 2023)	0.91
"The aim of this study was to compare the effects of constant rate infusions (CRI) of fentanyl alone or combined with lidocaine and ketamine (FLK), on physiological parameters, isoflurane requirements and the number of postoperative analgesic rescues in dogs undergoing unilateral mastectomy."	( Influence of Constant Rate Infusions of Fentanyl Alone or in Combination With Lidocaine and Ketamine on the Response to Surgery and Postoperative Pain in Isoflurane Anesthetized Dogs Undergoing Unilateral Mastectomy: A Randomized Clinical Trial. Alievi, MM; de Oliveira, TF; Herrera-Becerra, JR; Marques, ÉJ; Monteiro, ER; Rovaris, IB; Tomazeli, D; Valle, SF, )	0.13
" To evaluate the efficacy and safety of adding morphine to periarticular infiltration analgesia (PIA) combined with single-dose epidural morphine for the patients undergoing TKA."	( Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study. Cao, L; Gu, W; Guo, X; Li, Y; Wulamu, W; Yushan, N; Zhang, X, 2023)	1.5
"PIA combined with single-dose epidural morphine effectively reduces early postoperative pain and tramadol requirement as well as few complications, which can become a safe and effective measure to improve postoperative pain after TKA."	( Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study. Cao, L; Gu, W; Guo, X; Li, Y; Wulamu, W; Yushan, N; Zhang, X, 2023)	1.51
" We compared the analgesic efficacies of ultrasound-guided iPACK block and GNB when combined with continuous adductor canal block after total knee arthroplasty."	( Comparison of Analgesic Efficacies of the iPACK (Interspace Between the Popliteal Artery and Capsule of the Posterior Knee) and Genicular Nerve Blocks Used in Combination With the Continuous Adductor Canal Block After Total Knee Arthroplasty: A Randomized Kampitak, W; Kertkiatkachorn, W; Ngarmukos, S; Tanavalee, A; Tanavalee, C; Tangkittithaworn, C, 2023)	0.91
"To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases."	( Microwave ablation combined with vertebral augmentation under real-time temperature monitoring for the treatment of painful spinal osteogenic metastases. Bai, Y; Fan, J; Li, P; Qiu, Y; Wu, L; Yang, S; Yuan, Q; Zhang, K; Zhang, X, 2023)	0.91
"The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases."	( Microwave ablation combined with vertebral augmentation under real-time temperature monitoring for the treatment of painful spinal osteogenic metastases. Bai, Y; Fan, J; Li, P; Qiu, Y; Wu, L; Yang, S; Yuan, Q; Zhang, K; Zhang, X, 2023)	0.91
" More importantly, opioids are often prescribed in combination with multiple other drugs, especially in patient populations who typically are prescribed a large drug regimen."	( Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions. Coates, S; Lazarus, P, 2023)	1.2
"05 mg/cc morphine, administered with a basal infusion rate of 4 cc/h, a 2-cc bolus dose, and a 30-minute lockout time."	( Bupivacaine combined with morphine for patient-controlled epidural analgesia after thoracotomy: high volume and low concentration vs. low volume and high concentration. Baldemir, R; Cirik, MÖ; Kaybal, O; Küçük, O; Sazak, H; Tunç, M; Ülger, G, 2023)	1.63

Bioavailability

The absolute bioavailability of morphine in the oral solution was 21%. The morphine pharmacokinetics following administration of a specifically formulated controlled release suppository showed less variability (rectal bioavailability was 42%).

Excerpt	Reference	Relevance
" Hepatic morphine clearances at normal therapeutic doses parallel hepatic blood flow and explain the lack of oral morphine bioavailability by anticipating complete first-pass liver metabolism."	( Pharmacokinetics of morphine and its surrogates. III: Morphine and morphine 3-monoglucuronide pharmacokinetics in the dog as a function of dose. Garrett, ER; Jackson, AJ, 1979)	1
" Attempts to use pupil diameter to assess morphine bioavailability illuminate the fact that multiple responses, nonlinearities, and the condition of the subject can produce misleading results unless the applicability of the method is confirmed."	( Use of pharmacological data for bioavailability and pharmacokinetic analyses. Kramer, PA, 1977)	0.52
" Unlike morphine, the glucuronide conjugate in bile was poorly absorbed from the small intestine where its hydrolysis occurred slowly."	( Studies of the enterohepatic circulation of morphine in the rat. Levine, RR; Walsh, CT, 1975)	0.95
" Phamacokinetics of morphine from the suppository were compared with the orally administered MST, and it was found that there was no difference in the maximum plasma concentration (Cmax) and the peak time (Tmax) between MSC and MST, but the mean residence time (MRT) of MSC was approximately three times longer than that of MST, and the extent of bioavailability (BA) of MSC was significantly larger than that of MST (71."	( Bioavailability of morphine in rabbits after rectal administration of suppository containing controlled release morphine tablet. Adachi, I; Horikoshi, I; Kanamoto, I; Koizumi, T; Ueno, M; Zheng, NX, 1992)	0.94
"The effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR; Roxane Laboratories, Inc."	( An evaluation of the effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR) after multiple doses. Bass, J; Hulse, J; Lee, JW; Shepard, KV, 1992)	0.74
" We compared the bioavailability of two prototype 30-mg morphine sulfate controlled-release suppository formulations (high and low viscosity) with 30-mg oral controlled-release morphine sulfate tablets in a 14-subject single-dose randomized, three-way crossover study."	( Pharmacokinetics of two novel rectal controlled-release morphine formulations. Anslow, JA; Babul, N; Darke, AC; Krishnamurthy, TN, 1992)	0.78
"The bioavailability of controlled-release morphine 30-mg tablets (MSC) administered orally or rectally and immediate-release morphine (RMS) 30-mg suppositories per rectum, was compared in this 14-subject, randomized, single-dose, analytically blinded, crossover study."	( The bioavailability of morphine in controlled-release 30-mg tablets per rectum compared with immediate-release 30-mg rectal suppositories and controlled-release 30-mg oral tablets. Fitzmartin, RD; Goldenheim, PD; Kaiko, RF; Thomas, GB, 1992)	0.86
" Although the co-administration of tricyclic antidepressants may increase plasma morphine concentrations, any potentiation of morphine analgesia is thought not to be due to an increased bioavailability of the opiate, but to an intrinsic analgesic effect of antidepressants."	( Antidepressants in cancer pain. Bianchi, M; De Conno, F; Panerai, AE; Ripamonti, C; Sacerdote, P; Ventafridda, V, 1991)	0.51
" Ocular bioavailability of morphine is higher than after non-parenteral routes."	( Systemic morphine pharmacokinetics after ocular administration. Bardin, C; Callaert, S; Chast, F; Chaumeil, JC; Sauvageon-Martre, H, 1991)	1
" The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound."	( Pharmacokinetics of intramuscular nicomorphine and its metabolites in man. Booij, LH; Dirksen, R; Koopman-Kimenai, PM; Nijhuis, GM; Vree, TB, 1991)	0.55
" Hepatic insufficiency decreases the first-pass effect and therefore increases the bioavailability of oral morphine."	( [Pharmacokinetic effects in morphine toxicity, with case examples]. Morant, R; Senn, HJ, 1991)	0.79
" These data indicate that controlled-release morphine sulphate may be well absorbed in relation to the regular tablets."	( Plasma concentrations of morphine in children with chronic pain--comparison of controlled release and regular morphine sulphate tablets. Nahata, MC, 1991)	0.84
" The bioavailability of free morphine and the 6-glucuronated active metabolite was comparable through the different routes."	( Plasma morphine and morphine-6-glucuronide patterns in cancer patients after oral, subcutaneous, sublabial and rectal short-term administration. Bianchi, M; Breda, M; Panerai, AE; Ripamonti, C; Ventafridda, V; Zecca, E, 1991)	1.03
"The reproducibility in bioavailability of orally administered morphine (as a solution) under fed and fasted conditions was studied in 5 patients with chronic pain on three occasions over 1 yr (0, 6, and 12 mo)."	( The reproducibility of bioavailability of oral morphine from solution under fed and fasted conditions. Cherry, DA; Gourlay, GK; Plummer, JL; Purser, T, 1991)	0.78
"The bioavailability of a single, orally administered, 30-mg controlled-release morphine tablet (MS Contin Tablet; The Purdue Frederick Company, Norwalk, Conn."	( Controlled-release morphine bioavailability (MS Contin tablets) in the presence and absence of food. Cronin, C; Goldenheim, P; Grandy, R; Kaiko, RF; Lazarus, H; Thomas, G, 1990)	0.84
" The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group 2) for oxycodone hydrochloride, respectively."	( Morphine and oxycodone hydrochloride in the management of cancer pain. Kalso, E; Vainio, A, 1990)	1.93
" Although the bioavailability of morphine after rectal administration of morphine."	( [Morphine hydrochloride suppositories. II. Bioavailability of morphine hydrochloride suppositories in dogs]. Arakawa, S; Kitamura, K; Kojima, K; Nakanishi, Y; Tan, T; Yamanaka, M, 1990)	1.47
" Morphine bioavailability and morphine glucuronide production were not altered."	( Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Joel, S; Osborne, R; Slevin, M; Trew, D, 1990)	2.63
" The mean oral bioavailability was 101% (95% CI 56-147)."	( The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Eriksson, S; Hasselström, J; Persson, A; Rane, A; Säwe, J; Svensson, JO, 1990)	0.55
" The extent of bioavailability of morphine by rectal administration varied with the bases used (30."	( Studies on sustained-release suppositories. III. Rectal absorption of morphine in rabbits and prolongation of its absorption by alginic acid addition. Fujiwara, H; Inoue, Y; Kawashima, S; Shimeno, T, 1990)	0.79
" The method provides high sensitivity and selectivity and has been used successfully in bioavailability studies."	( Determination of opiates and other basic drugs by high-performance liquid chromatography with electrochemical detection. Band, C; Besner, JG; Caillé, G; Rondeau, JJ; Stewart, J; Varin, F; Yamlahi, L, 1989)	0.28
" The absolute bioavailability of morphine from oral aqueous solution, a controlled release oral tablet (MST-Continus) and a controlled release buccal tablet has been investigated in six healthy volunteers."	( The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers. Aherne, GW; Chapman, D; Filshie, J; Hanks, GW; Hoskin, PJ; Littleton, P, 1989)	0.82
" Under the conditions of this study there was no clinically significant difference in bioavailability between MSC and oral MSS."	( Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients. Besner, JG; Boos, GJ; Maroun, JA; Mount, BM; Sloan, PA; Stewart, JH; Thirlwell, MP, 1989)	0.53
" Part II presents three studies in which the MSC formulations (15-mg, 60-mg, and 100-mg tablets) were compared to the 30-mg tablet within three randomized, single-dose, two-way crossover, analytically blinded bioavailability protocols, to determine bioequivalence and dose proportionality."	( The United States experience with oral controlled-release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15-mg, 30-mg, 60-mg, and 100-mg tablet strengths in normal subjects. Goldenheim, PD; Grandy, RP; Horodniak, J; Ingber, E; Kaiko, RF; Oshlack, B; Pav, J; Thomas, G, 1989)	0.52
" In the in situ loop method, morphine was well absorbed in the order of jejunal site greater than duodenal site greater than ileal site greater than middle intestinal site greater than rectal site, but it was poorly absorbed from the stomach."	( Characteristics of the gastrointestinal absorption of morphine in rats. Imasato, Y; Kuramoto, M; Nakamura, H; Nakanishi, Y; Takahashi, T; Tan, T; Yoshimura, H, 1989)	0.82
" Similarly, clinical myotonolytic activity of eperisone would only be expected at high doses unless its functional bioavailability were to be much better in man than in either the mouse or rabbit."	( Comparison of the myotonolytic activity of tizanidine, eperisone and afloqualone in mouse and rabbit. Coward, DM; White, TG, )	0.13
" Peak plasma morphine concentrations were slightly lower after buccal than after intramuscular administration but they declined more slowly; consequently, the drug's bioavailability was 40-50% greater after buccal than after intramuscular administration."	( Buccal morphine--a new route for analgesia? Bell, MD; Calvey, TN; Mishra, P; Murray, GR; Weldon, BD; Williams, NE, 1985)	1.09
" Differences in absorption rate of 99mTc-EDTA, a poorly absorbable marker, were found, as morphine caused nearly all radioactive compound to be retained in the colon, while rhein significantly facilitated the transfer of marker from colon through mucosal barrier to blood."	( The antagonistic effect of morphine on rhein-stimulated fluid, electrolyte and glucose movements in guinea-pig perfused colon. Geeraerts, VC; Lemli, J; Verhaeren, EH, 1987)	0.79
" However, in both cases, levels of corticosterone in plasma were dramatically elevated, clearly demonstrating the bioavailability of the kappa agonists."	( The endogenous kappa agonist, dynorphin(1-13), does not alter basal or morphine-stimulated dopamine metabolism in the nigrostriatal pathway of the rat. Cosi, C; Iyengar, S; Kim, HS; Wood, PL, 1987)	0.51
"5 cm from the anus, 10 mg kg-1) administration of morphine hydrochloride were determined in 10 or 11-week-old male Wistar rats to compare bioavailability of morphine after the rectal dosage with that after oral administration."	( Enhanced bioavailability of morphine after rectal administration in rats. Itakura, T; Iwamoto, K; Kanba, Y; Katagiri, Y; Naora, K, 1988)	0.82
" Gastric emptying after each premedication was assessed indirectly from the rate of absorption of oral paracetamol."	( Comparison of the effect of cisapride and metoclopramide on morphine-induced delay in gastric emptying. Bamber, PA; Nimmo, WS; Rowbotham, DJ, 1988)	0.52
"The bioavailability of oral controlled release morphine tablets (MST, Napp Laboratories) and oral morphine sulphate in aqueous solution (MSS) was compared in 10 patients with advanced cancer."	( Relative bioavailability of controlled release morphine tablets (MST continus) in cancer patients. A-Omar, O; Aherne, GW; Hanks, GW; Hoskin, PJ; Johnston, A; Poulain, P; Turner, P; Walker, VA, 1988)	0.79
" The bioavailability of morphine after rectal administration was found to be 53."	( The bioavailability of rectally administered morphine. Christensen, CB; Frølund, C; Jonsson, T; Jordening, H, 1988)	0.84
" The oral bioavailability is approximately 40% with marked patient-to-patient variations as a result of differences in presystemic elimination."	( High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Säwe, J, )	0.53
" There were pronounced differences in oral bioavailability between the two opioids: methadone, 79 +/- 11."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.5
"The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively."	( Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. Evans, W; Khojasteh, A; Reynolds, RD; Savarese, JJ; Thomas, G, 1987)	0.81
" Serum morphine concentrations were measured (high pressure liquid chromatography) every 2 h for the first 16 h after surgery and the results were strongly suggestive of a decrease in the rate of absorption of morphine in this situation."	( Absorption of controlled release morphine sulphate in the immediate postoperative period. Achola, KJ; Derbyshire, DR; Pinnock, CA; Smith, G, 1986)	1.01
" Controlled release tablets had 86% the bioavailability of the solution."	( Steady-state pharmacokinetics of controlled release oral morphine sulphate in healthy subjects. Goldenheim, PD; Kaiko, RF; Savarese, JJ; Thomas, GB, )	0.38
" In accordance with previous results marked interindividual differences were seen in the kinetics of morphine; the oral bioavailability varied between 30 and 69% and the systemic plasma clearance between 18."	( Oral morphine in cancer patients: in vivo kinetics and in vitro hepatic glucuronidation. Kager, L; Rane, A; Säwe, J; Svensson Eng, JO, 1985)	1
" It is therefore recommended that further studies of the bioavailability of MST in the early postoperative period be undertaken before any recommendations are made regarding its routine use for pain relief at that time."	( Morphine sulphate slow release. Comparison with i.m. morphine for postoperative analgesia. Bell, A; Derbyshire, DR; Parry, PA; Smith, G, 1985)	1.71
"The analgesic effects and bioavailability of a slow-release preparation of morphine (Duromorph) were studied in 12 patients with acute postoperative pain."	( Postoperative analgesia with Duromorph. Calvey, TN; Charway, CL; Murray, GR; Williams, NE, 1985)	0.5
" The absorption rate and bioavailability could be greatly improved, as compared to orally administered morphine, by adjusting the pH."	( Drastic improvement in the rectal absorption profile of morphine in man. Meijer, DK; Moolenaar, F; Visser, J; Yska, JP, 1985)	0.73
" There were no significant differences between the tablets and the solution of morphine with regard to relative oral bioavailability or peak concentration."	( Steady-state kinetics and analgesic effect of oral morphine in cancer patients. Dahlström, B; Rane, A; Säwe, J, 1983)	0.75
"The bioavailability of codeine and extent of its transformation to morphine were stated in 12 smoking and 11 nonsmoking subjects after single doses 60 mg IM codeine and 60 mg codeine sulfate orally, given 1 wk apart."	( Codeine disposition in smokers and nonsmokers. Bustrack, JA; Butz, RF; Findlay, JW; Hull, JH; Jones, EC; Rogers, JF; Welch, RM, 1982)	0.5
" The relative codeine bioavailability in these groups was 54."	( An evaluation of the effects of smoking on codeine pharmacokinetics and bioavailability in normal human volunteers. Bustrack, JA; Butz, RF; Findlay, JW; Hull, JH; Rogers, JF; Welch, RM, 1982)	0.26
" There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half-life from 58 to 465 min."	( Morphine kinetics in cancer patients. Dahlström, B; Paalzow, L; Rane, A; Säwe, J, 1981)	1.71
" Oral naltrexone and nalmefene have significantly more central nervous system (CNS) bioavailability than oral naloxone."	( Orally administered opioid antagonists reverse both mu and kappa opioid agonist delay of gastrointestinal transit in the guinea pig. Culpepper-Morgan, JA; Holt, PR; Kreek, MJ; LaRoche, D, 1995)	0.29
" The absolute bioavailability of morphine in both IR and in CR tablets was, 32%, and the relative bioavailability of the CR tablet versus the IR tablets was 103% (91-115%, 95% confidence interval)."	( Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide after intravenous and oral administration to healthy volunteers: relationship to nonanalgesic actions. Höglund, P; Persson, C; Westerling, D, 1995)	0.88
"Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets."	( A bioequivalence study of oral controlled-release morphine using naltrexone blockade. Goldenheim, PD; Grandy, RP; Kaiko, RF; Reder, RF; Sackler, RS, 1995)	0.81
"A liquid solution of morphine is well absorbed via the rectal route."	( Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain. Bruera, E; De Conno, F; Hanson, J; MacEachern, T; Ripamonti, C; Saita, L, 1995)	0.82
" Bioavailability (F) for both oral dosages was approximately 20%."	( Pharmacokinetics of parenteral and oral sustained-release morphine sulphate in dogs. Dohoo, S; Donald, A; Tasker, RA, 1994)	0.53
" A combination of alpha-cyclodextrin and xanthan gum produced sustained plasma profiles of morphine along with an increased rectal bioavailability (more than 4 times)."	( Modification of rectal absorption of morphine from hollow-type suppositories with a combination of alpha-cyclodextrin and viscosity-enhancing polysaccharide. Arakawa, K; Irie, T; Kondo, T; Nakamura, K; Shibuya, M; Tanaka, J; Uekama, K, 1995)	0.78
" These findings may be explained in part by prolongation of meperidine bioavailability because of impairment of hepatic function."	( Meperidine in conjunction with cholescintigraphy to diagnose acute cholecystitis in a patient allergic to morphine. Fong, J; Gora, ML; Shih, WJ, 1994)	0.5
" This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%."	( Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates. Booij, LH; Dirksen, R; Koopman-Kimenai, PM; Vree, TB, 1994)	0.81
" The absolute bioavailability of transdermal morphine was 75% (65-85%; 95% CI)."	( Transdermal administration of morphine to healthy subjects. Höglund, P; Lundin, S; Svedman, P; Westerling, D, 1994)	0.84
" The bioavailability of sublingual and buccal opioids is better as the uptake of active drug is governed by local blood flow."	( [Are there indications for oral or sublingual administration of morphines?]. Spielvogel, C, 1994)	0.53
" Bioavailability of codeine using the dosed feed route increased with dose, varying from 10% to 25%, which was somewhat higher than the previously reported approximately 8% bioavailability using the gavage route."	( Codeine toxicokinetics in rats during a two-year dosed feed study. Barnes, ER; Dunnick, JK; Findlay, JW; Yuan, J, )	0.13
" The absolute bioavailability of morphine in the oral solution was 21."	( Morphine pharmacokinetics and effects on salivation and continuous reaction times in healthy volunteers. Frigren, L; Höglund, P; Westerling, D, 1993)	2.01
"The bioavailability of morphine after rectal administration using three types of suppositories containing morphine hydrochloride (10 mg) in different added forms was evaluated in rabbits."	( Difference in rectal absorption of morphine from hollow-type and conventional suppositories in rabbits. Matsumoto, M; Matsumoto, Y; Watanabe, Y; Yamamoto, I, 1993)	0.87
" Systemic bioavailability and peak plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide were significantly greater after oral morphine administration compared with the rectal route (AUC: M6G, 377."	( Disposition of morphine and its glucuronide metabolites after oral and rectal administration: evidence of route specificity. Babul, N; Darke, AC, 1993)	0.88
"Previous literature reports have suggested that sublingually administered morphine sulfate results in an improved bioavailability of the drug when compared to orally administered morphine."	( Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. Ames, MM; Burnham, NL; Davis, T; Dose, AM; Kaur, JS; Loprinzi, CL; Miser, AW, 1993)	0.9
"8 L/kg and oral bioavailability was 29."	( Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Hasselström, J; Säwe, J, 1993)	1.73
"The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was determined using a randomized, 2-way crossover, analytically blinded study design."	( Relative bioavailability of controlled-release oral morphine sulfate during naltrexone blockade. Bashaw, ED; Goldenheim, PD; Grandy, RP; Kaiko, RF; Reder, RF, 1995)	0.76
"29), suggesting it is directly related to the absorption rate of nicomorphine."	( The bioavailability of intramuscularly administered nicomorphine (Vilan) with its metabolites and their glucuronide conjugates in surgical patients. Booij, LH; Dirksen, R; Koopman-Kimenai, PM; Vree, TB, 1995)	0.77
" This investigation was carried out to evaluate the bioavailability of a recent sustained-release (SR) formulation of morphine sulphate (30 mg), Skenan, consisted of capsules, relative to a recognized product, Moscontin which is a matrix tablet SR form."	( Study of the bioequivalence of two controlled-release formulations of morphine. Bourget, P; Lesne-Hulin, A; Quinquis-Desmaris, V, 1995)	0.73
"The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or after a high-fat breakfast."	( Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus. Aliyar, CA; Crawford, FE; Drake, J; Gibson, P; Horth, CE; Kirkpatrick, CT, 1996)	0.53
"The mean rectal bioavailability of morphine was 35% (range 18-59) after hydrogel administration and 27% (range 6-93) after the solution."	( Rectal administration of morphine in children. Pharmacokinetic evaluation after a single-dose. Beck, O; Boreus, LO; Lundeberg, S; Olsson, GL, 1996)	0.87
" In combination with xanthan gum, alpha-cyclodextrin reduced the first-pass metabolism of morphine in the rectal mucosa and by the liver and improved the apparent rectal bioavailability of the opioid about 4 fold."	( Combination effects of alpha-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits. Irie, T; Kondo, T; Uekama, K, 1996)	0.73
" Bioavailability was estimated by dividing the morphine concentration AUC/dose by that obtained after intravenous morphine."	( Systemic absorption of nebulized morphine compared with oral morphine in healthy subjects. Masood, AR; Thomas, SH, 1996)	0.83
"The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight."	( Passive drug diffusion via standardized skin mini-erosion; methodological aspects and clinical findings with new device. Hammarlund, C; Höglund, P; Lundin, S; Malmros, C; Pantzar, N; Svedman, P, 1996)	0.29
"The oral bioavailability of morphine following administration of a single dose of 30 mg morphine hydrochloride as Vendal retard film tablets (Lannacher Heilmittel) was investigated and compared with the bioavailability of morphine following administration of 30 mg morphine sulphate as Mundidol retard film tablets (Mundipharma)."	( [Bioavailability of morphine after oral administration as retard tablets]. Beubler, E; Dittrich, P; Semmelrock, J; Wolf, G, 1996)	0.91
") bioavailability of the sublingual aerosol morphine was 19."	( A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers. Eden, OB; Joel, SP; Slevin, ML; Taylor, KM; Watson, NW, 1996)	0.81
" The ability of acylcarnitines to increase the transmeningeal flux of morphine in vitro suggests that lauroyl or myristoyl carnitine may increase the spinal bioavailability of morphine after epidural administration."	( Acylcarnitine chain length influences carnitine-enhanced drug flux through the spinal meninges in vitro. Bernards, CM; Ummenhofer, WC, 1997)	0.53
" The rate of absorption of morphine from the SR capsule was slower with food intake as evidenced by a 13% decrease in the maximum concentration (Cmax), a 28% increase in the half-life of absorption, and a 19% increase in the time to Cmax."	( The effect of food intake on the pharmacokinetics of sustained-release morphine sulfate capsules. Kaiko, RF, )	0.66
"5 to 2 g/kg of alcohol did not alter blood alcohol concentrations significantly, suggesting that the interactions between alcohol and naltrexone were unrelated to gross changes in alcohol metabolism or bioavailability factors."	( Interactions between alcohol- and opioid-induced suppression of rat testicular steroidogenesis in vivo. Adams, ML; Cicero, TJ; Meyer, ER, 1997)	0.3
" These data show that there are sex differences in the effects of ibogaine and that this may be due to decreased bioavailability of ibogaine in males as compared to females."	( Sex differences in ibogaine antagonism of morphine-induced locomotor activity and in ibogaine brain levels and metabolism. Boyd, DL; Glick, SD; Hough, LB; Pearl, SM, 1997)	0.56
"The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to each other and to a bolus injection of morphine sulfate (MS) intravenously (i."	( Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations. Dohoo, SE; Tasker, RA, 1997)	0.83
" The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%)."	( Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system. Farr, SJ; Lloyd, P; Mather, LE; Okikawa, JK; Rubsamen, RM; Schuster, JA; Ward, ME; Woodhouse, A, 1997)	1.98
" The use of a penetration enhancer is required to improve the bioavailability of the drug via buccal route."	( In vitro studies on enhancing effect of sodium glycocholate on transbuccal permeation of morphine hydrochloride. Capan, Y; Duchêne, D; Hincal, AA; Ponchel, G; Senel, S, 1998)	0.52
"A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet."	( Bioavailability of morphine after administration of a new bioadhesive buccal tablet. Aiache, JM; Beyssac, E; Jacob, L; Meyer, M; Sandouk, P; Touaref, F, 1998)	0.93
" The morphine pharmacokinetics following administration of a specifically formulated controlled release suppository showed less variability (rectal bioavailability was 42%)."	( Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine. Gourlay, GK, 1998)	1.05
"3%), indicating a 36% reduction in the bioavailability of trovafloxacin."	( The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects. Friedman, HL; Hunt, T; Robarge, L; Teng, R; Vincent, J; Willavize, SA, 1998)	0.55
"Coadministration of trovafloxacin and morphine reduces the bioavailability and maximum serum concentrations of trovafloxacin."	( The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects. Friedman, HL; Hunt, T; Robarge, L; Teng, R; Vincent, J; Willavize, SA, 1998)	0.82
" Of this, 42+/-8% passed through the liver, resulting in an oral bioavailability of morphine of 34+/-9%."	( Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Ahne, G; Geisslinger, G; Kobal, G; Lötsch, J; Weiss, M, 1999)	0.76
"A decrease in the rate of gastric emptying can delay resumption of enteral feeding, alter bioavailability of orally administered drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting."	( Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine. Cooke, T; Duggan, F; Lydon, AM; Shorten, GD, 1999)	0.54
"These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e."	( The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration. France, CP; Gauthier, CA, 1999)	0.54
"To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs."	( Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs. Barnhart, MD; Bednarski, RM; Hubbell, JA; Muir, WW; Sams, RA, 2000)	0.75
" Overall systemic bioavailability of morphine administered per rectum was 19."	( Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs. Barnhart, MD; Bednarski, RM; Hubbell, JA; Muir, WW; Sams, RA, 2000)	0.82
"Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs."	( Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs. Barnhart, MD; Bednarski, RM; Hubbell, JA; Muir, WW; Sams, RA, 2000)	0.85
" The presence of other elimination organs did not affect the intestinal clearance and bioavailability estimates, but reduced the percentage of dose metabolized by the intestine."	( A new physiologically based, segregated-flow model to explain route-dependent intestinal metabolism. Cong, D; Doherty, M; Pang, KS, 2000)	0.31
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min."	( Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Connors, PM; Dershwitz, M; Morishige, RJ; Rosow, CE; Rubsamen, RM; Shafer, SL; Walsh, JL, 2000)	0.54
" Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form."	( Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Connors, PM; Dershwitz, M; Morishige, RJ; Rosow, CE; Rubsamen, RM; Shafer, SL; Walsh, JL, 2000)	1.45
" The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine."	( Morphine or oxycodone in cancer pain? Heiskanen, TE; Kalso, EA; Ruismäki, PM; Seppälä, TA, 2000)	2.05
"Although liposome encapsulation prolongs the duration of action of epidurally administered drugs, little is known about how liposome encapsulation affects opioids differently, or about how lipid content of liposomes alters the bioavailability of epidurally-administered opioids."	( The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo. Bernards, CM; Bethune, CR; Bui-Nguyen, T; Ho, RJ; Shen, DD, 2001)	0.31
" Bioavailability of MNTX is low after oral administration, and plasma levels do not correlate with its actions in the gut, suggesting a predominantly local luminal action of MNTX on the gut."	( A review of the potential role of methylnaltrexone in opioid bowel dysfunction. Foss, JF, 2001)	0.31
"Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration."	( Intranasal delivery of morphine. Davis, SS; Fisher, AN; Hinchcliffe, M; Illum, L; Jabbal-Gill, I; Nankervis, R; Norbury, H; Watts, P, 2002)	2.07
"This study compared the bioavailability of MSER and its metabolites morphine-3-glucuronide and morphine-6-glucuronide after administration of MSER in a sprinkle-dose regimen relative to an intact capsule swallowed whole."	( Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation. Butler, J; Devane, J; Eliot, L; Loewen, G, 2002)	0.77
" MSER and CRM demonstrated similar bioavailability (AUC) of morphine and its metabolites."	( Steady-state pharmacokinetic comparison of a new, extended-release, once-daily morphine formulation, Avinza, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain. Butler, J; Devane, J; Eliot, L; Loewen, G; Portenoy, RK; Sciberras, A, 2002)	0.78
" This "ceiling" effect may be the result of saturation of opioid receptors in the lung, the variable bioavailability of inhaled morphine, or a placebo response."	( Nebulized morphine as a treatment for dyspnea in a child with cystic fibrosis. Cohen, SP; Dawson, TC, 2002)	0.92
" Intraperitoneal administration of morphine reduced the bioavailability compared to intravenous and subcutaneous administration, but not so for morphine-glucuronides."	( Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity. Grung, M; Handal, M; Mørland, J; Ripel, A; Skurtveit, S, 2002)	0.88
") administration to SOP rabbits was almost the same as that in normal rabbits, suggesting that an increase in the rate of absorption of morphine in SOP rabbits was not due to inflammation at the absorption site caused by operation, but probably due to its increased solubility in loose stools."	( Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits. Fujimoto, S; Kintsuji, S; Nagai, K; Nagasawa, K; Nakanishi, H, 2003)	0.84
" These observations are attributed to the greater effects of noninstantaneous mixing of drugs for jugular vein sampling following nasal dosing, compared to the other sampling sites, which is significant for drugs that are rapidly and well absorbed and that have a high volume of distribution (Vd)."	( The effect of blood sampling site and physicochemical characteristics of drugs on bioavailability after nasal administration in the sheep model. Davis, SS; Hinchcliffe, M; Illum, L, 2003)	0.32
"The aim of this study was to determine the influence of the type of paracetamol formulation on the rate of absorption when subjects are in the supine position, with or without taking concomitant morphine."	( The influence of morphine on the absorption of paracetamol from various formulations in subjects in the supine position, as assessed by TDx measurement of salivary paracetamol concentrations. Davey, AK; Kennedy, JM; Tyers, NM, 2003)	0.85
" In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers."	( The bioavailability of morphine applied topically to cutaneous ulcers. Joel, SP; Ribeiro, MD; Zeppetella, G, 2004)	0.87
" morphine-induced systemic skin scratching and is more readily absorbed intragastrically than is U-50488H, resulting in high bioavailability in the intragastric route."	( Inhibitory effects of TRK-820 on systemic skin scratching induced by morphine in rhesus monkeys. Endoh, T; Fujiwara, A; Nagase, H; Okano, K; Tanaka, T; Umeuchi, H; Wakasa, Y, 2004)	1.47
" Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method."	( Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma. El-Kabsh, MY; El-Kady, SA; Emara, SE; Fouad, EA; Kotb, HI, 2005)	0.6
"Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64."	( Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma. El-Kabsh, MY; El-Kady, SA; Emara, SE; Fouad, EA; Kotb, HI, 2005)	2.04
" A mean bioavailability of 78% was estimated; the total clearance averaged 41 L/h."	( Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients. Bressolle, F; Caumette, L; Culine, S; Garcia, F; Pinguet, F; Poujol, S; Solassol, I, 2005)	0.33
" Oral bioavailability was 5% as determined from naïve-averaged analysis."	( Pharmacokinetics of morphine and plasma concentrations of morphine-6-glucuronide following morphine administration to dogs. KuKanich, B; Lascelles, BD; Papich, MG, 2005)	0.65
" Mean residence time of morphine was considerably prolonged without changing relative bioavailability in the case of the mixed base suppositories containing 15-17% HB750, compared with the Witepsol H15 suppository, clearly indicating that the mixed bases containing HB750 are expected to be useful for the design of controlled-release morphine suppositories."	( Design of controlled-release morphine suppositories containing polyglycerol ester of fatty acid. Higaki, K; Kimura, T; Takatori, T; Yamaguchi, T; Yamamoto, K, 2005)	0.93
"The bioavailability of inhaled heroin was estimated to be 53% (95% CI 43."	( Population pharmacokinetics of heroin and its major metabolites. Beijnen, JH; Huitema, AD; Rook, EJ; van den Brink, W; van Ree, JM, 2006)	0.33
" This efficient route enabled to scale up the synthesis of an orally bioavailable glycine antagonist showing outstanding in vivo anti-hyperalgesic activity in different animal models of sustained inflammation and chronic neuropathic pain."	( Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain. Alvaro, G; Barnaby, RJ; Bertani, B; Corsi, M; Di Fabio, R; Donati, D; Gentile, G; Giacobbe, S; Pentassuglia, G; Pizzi, DM; Quartaroli, M; Ratti, E; Spada, S; Vitulli, G, 2007)	0.34
" Relative bioavailability following SPILA granules administration to twice-a-day MS Contin (30 mg) administration was 131%."	( Pharmacokinetic and pharmacodynamic evaluations of novel oral morphine sustained release granules. Akiyama, Y; Fuse, T; Nakamura, K; Nara, E, 2007)	0.58
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."	( Hologram QSAR model for the prediction of human oral bioavailability. Andricopulo, AD; Moda, TL; Montanari, CA, 2007)	0.34
" They constitute the first report of a demonstration of the effect of the EHC on morphine bioavailability in an addict, and could be considered as indication, without supporting circumstantial evidence, that the morphine level in bile is related to chronic opiate use."	( Bile analysis in heroin overdose. Cacaci, C; Froldi, R; Tassoni, G; Zampi, M, 2007)	0.57
" Naloxone, an opiate antagonist, is very poorly absorbed with sublingual administration, but if it is injected intravenously, it will antagonise the effects of buprenorphine."	( Buprenorphine + naloxone: new combination. Opiate dependence: no proof of reduced risk of self-administered injection. , 2007)	0.34
" Topical morphine might provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans."	( Morphine bioavailability from a topical gel formulation in volunteers. Avram, MJ; Hudgins, JC; Krejcie, TC; Luong, L; Paice, JA; Von Roenn, JH, 2008)	2.21
" The present study was undertaken to assess the single-dose relative bioavailability of polymer-coated, extended-release morphine sulfate capsules (KADIAN, 100 mg; Alpharma Pharmaceuticals LLC, Piscataway, NJ)."	( Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules. Johnson, F; Stauffer, J; Sun, S; Wagner, G, 2008)	0.78
"The bioavailability of morphine sulfate extended-release capsules is not compromised when taken with food and dose dumping (immediate elevations in dose) does not occur when morphine sulfate extended-release capsules are taken concomitantly with alcohol."	( Morphine sulfate extended-release capsules for the treatment of chronic, moderate-to-severe pain. Nicholson, B, 2008)	2.1
" Morphine bioavailability after high-dose oral diacetylmorphine is considerably higher than would be predicted from low-dose trials."	( Oral diacetylmorphine (heroin) yields greater morphine bioavailability than oral morphine: bioavailability related to dosage and prior opioid exposure. Diterich, I; Eich-Höchli, D; Fattinger, K; Halbsguth, U; Rentsch, KM, 2008)	1.63
" However, morphine bioavailability was considerably higher in chronic users [diacetylmorphine 45."	( Oral diacetylmorphine (heroin) yields greater morphine bioavailability than oral morphine: bioavailability related to dosage and prior opioid exposure. Diterich, I; Eich-Höchli, D; Fattinger, K; Halbsguth, U; Rentsch, KM, 2008)	1.12
" Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management."	( Pediatric palliative care: use of opioids for the management of pain. Anderson, BJ; Craig, F; Michel, E; Zernikow, B, 2009)	0.35
" Recently, we described a novel series of potent, selective, and orally bioavailable delta opioid receptor agonists."	( Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) benzamide (ADL5747). Ajello, CW; Barker, WM; Belanger, S; Brogdon, BL; Cassel, JA; Chu, GH; DeHaven, RN; DeHaven-Hudkins, DL; Derelanko, MJ; Dolle, RE; Feschenko, MS; Graczyk, TM; Gu, M; Koblish, M; Kutz, S; Le Bourdonnec, B; Leister, LK; Little, PJ; Smith, SA; Tuthill, PA; Wiant, DD; Windh, RT; Zhou, QJ, 2009)	0.35
" Concomitant SC administration of rHuPH20 enhanced the absorption rate of morphine compared with SC morphine with placebo, significantly reducing the mean T(max) from 13."	( The INFUSE-Morphine study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneously administered morphine in patients with advanced illness. Flament, J; Haller, MF; Thomas, JR; Vaughn, DE; Wallace, MS; Yocum, RC, 2009)	0.97
" Morphine regulates NO bioavailability in various organs."	( Interactions between morphine and nitric oxide in various organs. Hatano, Y; Kishioka, S; Toda, H; Toda, N, 2009)	1.58
"The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution."	( Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, thr Bieberdorf, FA; Johnson, FK; Stark, JG; Stauffer, J, 2010)	0.64
" The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%."	( Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, thr Bieberdorf, FA; Johnson, FK; Stark, JG; Stauffer, J, 2010)	0.64
" The primary objective of this study was to assess single-dose relative bioavailability of morphine when morphine sulfate and naltrexone hydrochloride extended release capsules were taken under fed and fasting conditions and when pellets were sprinkled on apple sauce."	( Food effects on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, F; Stauffer, J; Swearingen, D, 2010)	0.85
"Morphine bioavailability was similar for all treatments."	( Food effects on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, F; Stauffer, J; Swearingen, D, 2010)	2.07
" When PK parameters were grouped as low-medium-high, clearance, volume of distribution, half life and bioavailability were similar between discrete and cassette analysis for 90%, 86%, 95% and 90% of the total number of compounds tested, respectively."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
" This open-label, single-dose, 4-way crossover, pharmacokinetic drug interaction study compared the relative bioavailability of morphine and naltrexone when MS-sNT is administered (under fasting conditions) with increasing doses of alcohol."	( Effects of alcohol on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, FK; Kisicki, J; Stauffer, J, 2012)	0.84
"The naltrexone bioavailability study compared naltrexone release from MS-sNTC with that from whole intact MS-sNT capsules (MS-sNTW) and an equal naltrexone solution (NS) dose."	( Morphine sulfate and naltrexone hydrochloride extended-release capsules: naltrexone release, pharmacodynamics, and tolerability. Johnson, F; Setnik, B, )	1.57
"Naltrexone from MS-sNTC met criteria for equivalent bioavailability to NS."	( Morphine sulfate and naltrexone hydrochloride extended-release capsules: naltrexone release, pharmacodynamics, and tolerability. Johnson, F; Setnik, B, )	1.57
"028 L·min⁻¹·kg⁻¹, and the absolute bioavailability of inhaled morphine was 35."	( The pharmacokinetics of inhaled morphine delivered by an ultrasonic nebulizer in ventilated dogs. Ge, W; Pan, L; Wang, X; Xu, X; Zheng, M, 2012)	0.9
" Their impact on oral pharmacotherapy, including their effect on the bioavailability of oral medications, is poorly understood."	( Unpredictable absorption of oral opioid medications in a quadriplegic patient with chronic enterocutaneous fistulas. Viswesh, VV, 2012)	0.38
"The combined decrease in Ago2 and increases in Nurr1 and Pitx3 might represent some of the mechanisms that served to protect against accumbal TH regulation observed in morphine withdrawn rats, which may be critical for DA bioavailability to influence behaviour."	( Morphine administration modulates expression of Argonaute 2 and dopamine-related transcription factors involved in midbrain dopaminergic neurons function. García-Pérez, D; Laorden, ML; Milanés, MV; Núñez, C; Sáez-Belmonte, F, 2013)	2.03
" Moreover, the intravenous titration option used in the study provided a clean collection of pharmacokinetic surrogate data of morphine along with its metabolites without the issue of absorption and/or oral bioavailability setback if morphine was given by oral route."	( Do we have clarity on the therapeutic levels of morphine and its metabolites: seeking answers for the dilemma? Srinivas, NR, 2013)	0.85
" This study characterized the bioavailability of these drugs following buccal administration to cats."	( Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats. Ilkiw, JE; Pypendop, BH; Shilo-Benjamini, Y, 2014)	0.73
" That is, morphine and quinidine significantly increased the bioavailability of etoposide believed to be due to competitive P-gp inhibition in the intestine."	( Pharmacokinetic assessment of absorptive interaction of oral etoposide and morphine in rats. Iwanaga, K; Kakemi, M; Minamida, M; Miyazaki, M; Nishimura, C, 2014)	1.04
" As a result, repeated ETP dosing without MOR showed a significant decrease in the intestinal absorption rate constant (ka), and single MOR coadministration induced an increase in bioavailability (F) and decrease in ka."	( Pharmacokinetics and toxicity of repeated oral etoposide is altered by morphine coadministration in rats. Iwanaga, K; Kakemi, M; Kawase, T; Kitamura, T; Miyazaki, M; Nishimura, C, 2015)	0.65
"It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs."	( Influence of bile acid derivates on morphine analgesic effect in mice. Budakov, Z; Mikov, I; Mikov, M; Milijasević, B; Stilinović, N; Vasović, V; Vukmirović, S, 2014)	0.68
"6h, clearance 78 L/h [relative standard error (RSE) 12%] and absolute bioavailability 24% (RSE 11%)."	( Population pharmacokinetics of morphine and morphine-6-glucuronide following rectal administration--a dose escalation study. Brokjær, A; Christrup, LL; Dahan, A; Drewes, AM; Kreilgaard, M; Olesen, AE; Simonsson, US, 2015)	0.7
" In this paper, we expand on our original series by presenting two modifications, both of which were designed with the following objectives: (1) probing bioavailability and improving metabolic stability, (2) balancing affinities between MOR and DOR while reducing affinity and efficacy at the κ-opioid receptor (KOR), and (3) improving in vivo efficacy."	( Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities. Anand, JP; Griggs, NW; Harland, AA; Jutkiewicz, EM; Mosberg, HI; Pogozheva, ID; Traynor, JR; Yeomans, L, 2015)	0.42
" Therefore, this study highlights that both peculiar biological profile and bioavailability of such ligands complement each other to modulate the reduction of morphine tolerance."	( Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation. Caprioli, G; Comi, E; Del Bello, F; Domi, E; Ferrari, F; Galimberti, C; Giannella, M; Lanza, M; Mammoli, V; Mennuni, L; Milia, C; Pigini, M; Ricciutelli, M; Sabatini, C; Sagratini, G; Ubaldi, M, 2015)	0.85
" The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO)."	( Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium. Gauda, E; Gobburu, J; Ivaturi, V; Lewis, T; Liu, T, 2016)	0.7
"Systemic inflammation may change the bioavailability and pharmacokinetics of opioids."	( Effects of Low-Dose Escherichia coli Lipopolysaccharide-Induced Endotoxemia on Morphine Pharmacokinetics in an Animal Model. Billert, H; Grabowski, T; Grześkowiak, E; Lisiecka, J; Michalak, M; Szkutnik-Fiedler, D; Urjasz, H, 2016)	0.66
" Dose dependencies were found for morphine absorption rate and gabapentin bioavailability."	( Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat. Gabel-Jensen, C; Juul, RV; Kreilgaard, M; Lund, TM; Papathanasiou, T, 2016)	0.98
"Glycosylation by simple sugars is a drug discovery alternative that has been explored with varying success for enhancing the potency and bioavailability of opioid peptides."	( Role of the sugar moiety on the opioid receptor binding and conformation of a series of enkephalin neoglycopeptides. Arévalo, JC; Arsequell, G; Barreto-Valer, K; Calle, LP; Gonzalez-Nunez, V; Jiménez-Barbero, J; Marcelo, F; Rodríguez, RE; Rosa, M; Sánchez-Sánchez, J; Valencia, G, 2017)	0.46
" As the bioavailability of each opioid has a certain extent of interindividual bioavailability this conversion represents an approximation."	( Oral oxycodone for pain after caesarean section: A randomized comparison with nurse-administered IV morphine in a pragmatic study. Arnelo, C; Blanck, A; Niklasson, B; Öhman, SG; Segerdahl, M, 2015)	0.63
" Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine."	( Relative Oral Bioavailability of an Abuse-deterrent, Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period, Single-dose, Randomized Crossover Study in Healthy Subjects. Aigner, S; Kinzler, ER; Pantaleon, C, 2018)	0.96
"This single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy adult subjects compared the relative bioavailability of morphine ARER 100 mg to that of ER morphine 100 mg in the fasted condition."	( Relative Oral Bioavailability of an Abuse-deterrent, Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period, Single-dose, Randomized Crossover Study in Healthy Subjects. Aigner, S; Kinzler, ER; Pantaleon, C, 2018)	0.9
"Failure to recognize the impact of various situations described throughout this work, including the bioavailability due to loss of oral route, due to pharmacokinetics and pharmacodynamics of the various drugs, either in the context of the impaired metabolism or excretion, or in due to pharmacological interactions, conditions a serious risk of subtreatment of pain and consequent impact in terms of quality of life."	( [Opioids for Cancer Pain and its Use under Particular Conditions: A Narrative Review]. Brás, M; Fragoso, M; Vieira, C, 2019)	0.51
"TRV734 is an orally bioavailable G-protein-biased ligand at the μ-opioid receptor."	( A First-in-Human Clinical Study With TRV734, an Orally Bioavailable G-Protein-Biased Ligand at the μ-Opioid Receptor. Fossler, MJ; James, IE; Ramos, KA; Ruff, D; Skobieranda, F; Soergel, DG, 2020)	0.56
" Additionally, because of the very low oral bioavailability of naloxone, an oral formulation is not currently available."	( Novel Oral Nanoparticle Formulation of Sustained Release Naloxone with Mild Withdrawal Symptoms in Mice. Arora, M; Eitan, S; Kumar, MNVR; Madison, CA, 2020)	0.56
" To develop stable and orally bioavailable analogues of DN-9, eight lactam-bridged cyclic analogues of DN-9 between positions 2 and 5 were designed, synthesized, and biologically evaluated."	( Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects. Chen, D; Fang, Q; Li, N; Niu, J; Shi, X; Shi, Y; Xiao, J; Xu, B; Xu, K; Zhang, M; Zhang, Q; Zhang, R, 2021)	0.62
" Ferulic acid (FA), a phenolic phytochemical found in a variety of foods, has been reported to exert antioxidant and neuroprotective effects; however, its low bioavailability makes its nano-encapsulated form a promising alternative."	( Ferulic acid-loaded nanostructure prevents morphine reinstatement: the involvement of dopamine system, NRF2, and ΔFosB in the striatum brain area of rats. Burger, ME; D'avila, LF; de Bona da Silva, C; Metz, VG; Milanesi, LH; Pereira, VG; Rampelotto, CR; Rosa, JLO; Rossato, DR; Schaffazick, SR, 2023)	1.17

Dosage Studied

The correct dosage of lactulose for the prevention of oral morphine-induced constipation is 60 ml/d. For both morphine and ziconotide, the PACC guidelines recommend conservative initial dosing strategies. We conclude that morphine is clinically effective at this dosage range.

Excerpt	Relevance	Reference
" Dose-response curves for locomotor activity were also determined with morphine and methadone administered intraventricularly."	( Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. Davis, DC; Holtzman, SG; Shannon, HE, 1976)	0.49
" Dose-response data revealed essentially the same ED50's for naloxone in both tests."	( Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice. Smits, SE, 1976)	0.56
" The discriminative effects of morphine, measured by responding on the morphine-appropriate lever, were then evaluated by determining the dose-response characteristics of representative narcotic analgesics, analgesics with mixed agonist and narcotic antagonist properties and nonopioid psychoactive drugs."	( Further evaluation of the discriminative effects of morphine in the rat. Holtzman, SG; Shannon, HE, 1977)	0.79
" Unfortunately, the occurrence of psychotomimetic side effects prevented the administration of doses of Win 20,836 equieffective with the morphine standard, and this necessitated substantal extrapolation of the dose-response curve of the test drug to arrive at a relative potency estimate."	( Twin crossover relative potency analgesic assays in man. II. Morphine vs. 8-methoxycyclazocine. Beaver, WT; Feise, GA, )	0.58
" Dose-response and time-effect curves were determined for morphine (1."	( Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat. Holtzman, SG; Schaefer, GJ, 1977)	0.5
" 2 In the absence of morphine the inhibitory effects of the presynaptic alpha-adrenoceptor agonists, clonidine and oxymetazoline were much reduced and the dose-response curve was flat."	( The inhibitory effects of presynaptic alpha-adrenoceptor agonists on contractions of guinea-pig ileum and mouse vas deferens in the morphine-dependent and withdrawn states produced in vitro. Gillan, MG; Kosterlitz, HW; Robson, LE; Waterfield, AA, 1979)	0.78
" Dose-response studies indicated that sensitivity to morphine's rewarding property was decreased by frontal cortical and hippocampal lesions."	( Changes in morphine self-administration after tel-diencephalic lesions in rats. Cox, RD; Glick, SD, 1978)	0.9
" In the second series of experiments the dose-response curve of morphine for the motor activity has been found to shift to the left by the pretreatment of mice with 10 mg/kg of THC."	( Interaction between delta 9-tetrahydrocannabinol and morphine on the motor activity of mice. Ayhan, IH; Kaymakçalan, S; Tulunay, FC, 1979)	0.75
" Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine."	( Studies on tolerance development to single doses of morphine in mice. Huidobro, F; Huidobro-Toro, JP; Leong Way, E, 1976)	0.73
"1 Dose-response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus-longitudinal muscle strip preparations from normal and morphine pretreated guinea-pigs."	( Opiate binding and effect in ileum preparations from normal and morphine pretreated guinea-pigs. Cox, BM; Padhya, R, 1977)	0.78
" Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone."	( The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA. Besson, JM; Guilbaud, G; Le Bars, D; Menetrey, D; Rivot, JP, 1979)	0.75
" For compounds with dual agonist and antagonist properties, the dose-response curves for agonist activity are shallow."	( Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics. Hughes, J; Kosterlitz, HW; Leslie, FM, 1975)	0.66
" With l-dopa it was antogonised when the dose of morphine was minimal but with increased dosage of morphine, there was no significant effect."	( Morphine analgesia and its modification by drugs altering serotonin (5-HT) and dopamine levels in the brain. Gupta, SK; Shinde, S, )	1.83
" The three diarrheal agents, administered intraperitoneally, showed dose-dependent and parallel dose-response curves with the following order of decreasing potency: PGF2 alpha, methacholine and 5-HTP."	( Naloxone reversal of drug-induced diarrhea in mice. Bertermann, RE; Dajani, EZ; Roge, EA; Schweingruber, FL; Woods, EM, 1979)	0.26
" Dose-response studies indicated that sensitivity to morphine's rewarding property was increased by substantia nigra lesions and decreased by medial raphe lesions."	( Changes in morphine self-administration after brainstem lesions in rats. Cox, RD; Glick, SD, 1977)	0.9
" In contrast, the morphine dose-response relationship was linear."	( The animal pharmacology of buprenorphine, an oripavine analgesic agent. Cowan, A; Doxey, JC; Harry, EJ, 1977)	0.59
"Tolerance to various effects of morphine in the rat can be quantified by means of a shift of semi-logarithmic dose-response curves."	( The development of tolerance to morphine in the rat. Coper, H; Fernandes, M; Kluwe, S, 1977)	0.82
" New dose-response curves indicated that tolerance developed to the morphine-induced discriminative stimulus, and to the analgesic action of morphine, but doses of morphine that failed to cause detectable analgesia still produced a pronounced discriminative stimulus."	( Tolerance to morphine-produced discriminative stimuli and analgesia. Lal, H; Miksic, S, 1977)	0.86
" Naloxone (5-500 microgram/kg) uniformly produced a dose dependent, parallel shift of the morphine dose-response curves to right."	( A dose ratio comparison of the interaction between morphine and cyclazocine with naloxone in rhesus monkeys on the shock titration task. Rudy, TA; Yaksh, TL, 1977)	0.73
" When the dosage in children receiving morphine as premedication before surgery is based on kilograms of body weight, there are only minor differences in the kinetic patterns of morphine at different ages (0 to 1, 1 to 7, and 7 to 15 yr)."	( Morphine kinetics in children. Bolme, P; Dahlström, B; Feychting, H; Noack, G; Paalzow, L, 1979)	1.97
"Continuous intravenous infusion of morphine in a dosage varied according to the changing needs of the patient is proposed as an ideal method of controlling postoperative pain and reducing postoperative respiratory complications."	( Measurement and control of postoperative pain. Nayman, J, 1979)	0.54
" In this series of experiments, the actions of morphine on BP, heart rate (HR) and pupillary diameter were re-examined in sedated, paralyzed cats under 2 ranges of dosage and 3 types of sedative."	( Biphasic effects of morphine on cardiovascular system of the cat. Wallenstein, MC, 1979)	0.84
" dose-response relationships induced by repeated opioid administration."	( Quantitative assessment of tolerance to and dependence on morphine in mice. Coper, H; Fernandes, M; Kluwe, S, 1977)	0.5
" L-5418 had an inhibitory effect on tonic convulsions induced by pentetrazol and N-sulfamoyl-hexahydroazepine (SaH 41-178), but not on clonic convulsions by those compounds at even a high dosage or on clonic convulsions induced by picrotoxin and bemegride."	( Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect. Fujimura, H; Go, K; Tsurumi, K, 1978)	0.26
"To date there has been no description of the hemodynamic dose-response relationship between enflurane and sodium nitroprusside (SNP), although these drugs are often used together to induce deliberate hypotension."	( Sodium nitroprusside: hemodynamic dose-response during enflurane and morphine anesthesia. Bedford, RF, )	0.37
"Guinea pigs were injected SC for 3 weeks with 3 different dosage schedules of morphine or methadone, or with saline."	( Time course of dopaminergic hypersensitivity following chronic narcotic treatment. Almasi, J; Carlson, KR, 1979)	0.49
") dosing produced only a slight cross-tolerance to the rate-decreasing effects of anileridine and alphaprodine."	( Comparing the effects of anileridine, alphaprodine and fentanyl on schedule-controlled responding by pigeons. Leander, JD, 1978)	0.26
" In the rats, naloxone administered systemically in doses of 10--100 microgram/kg produced a parallel shift in the dose-response curves of both nociceptive measures suggesting a competitive antagonism."	( Antinociceptive effects of intrathecally administered human beta-endorphin in the rat and cat. Henry, JL; Yaksh, TL, 1978)	0.26
" Both dose-response and time-duration studies were conducted."	( Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine. Elchisak, MA; Harry, GJ; Rosecrans, JA, 1977)	1.7
" Naloxone caused a parallel shift to the right of the dose-response curve for morphine."	( Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum. Coupar, IM, 1978)	0.85
" Brain morphine concentration and tail-flick latency both increased with increasing dosage over the first 3 days of the 6-day infusion regimen."	( Disposition of morphine in chronically infused rats: relationship to antinociception and tolerance. Daves, ED; Dewey, WL; Harris, LS; Huger, FP; Patrick, GA, 1978)	1.07
" Based on these results we recommend an individual, Sisomicin dosage for each age group."	( [Pharmacokinetic investigations on sisomicin in children (author's transl)]. Patsch, R; Richter, J; Sitka, U; Weingärtner, L, 1978)	0.26
" The study was double-blind, and the drugs were given IM at several dosage levels."	( Butorphanol and morphine: a double-blind comparison of their parenteral analgesic activity. Caruso, FS; Corssen, G; Tavakoli, M, )	0.48
" Dosage forms of small implantable cylinders, 1/16'' diameter, (25 mg/rod, one rod/mouse) containing 33% by weight naltrexone pamoate in 90 L(+)/10 polylactic/glycolic acid have sustained the delivery of chemical for 20 days."	( Development of polylactic/glycolic acid delivery systems for use in treatment of narcotic addiction. Howes, JF; Schwope, AD; Wise, DL, 1976)	0.26
" Dose-response analyses of the effects of d-amphetamine, an indirectly acting dopamine agonist, and apomorphine, a directly acting dopamine agonist, revealed a shift in the dose-response curves following chronic morphine treatment, indicating that the animals were supersensitive to these agents."	( Alterations in the effects of dopamine agonists and antagonists on general activity in rats following chronic morphine treatment. Overstreet, DH; Smee, ML, 1976)	0.68
" The dose-response relationship of the MF rats, thus, clearly differed from that of the hypothalamic rats."	( Comparison of the effects of morphine on hypothalamic and medial frontal cortex self-stimulation in the rat. Lorens, SA, 1976)	0.55
"The use of pharmacological responses such as pupil diameter for dosage individualization, bioavailability, and pharmacokinetic analyses is becoming more widespread."	( Use of pharmacological data for bioavailability and pharmacokinetic analyses. Kramer, PA, 1977)	0.26
" Cumulative dose-response curves for morphine and for morphine after naloxone yielded the value pA2=6."	( Miosis and fluctuation in the rabbit pupil: effects of morphine and naloxone. Adler, MW; Kester, RA; Kramer, MS; Murray, RB; Roy, JW; Tallarida, RJ, 1977)	0.78
"A biphasic dose-response pattern is generated by the isoquinoline, 3-carboxysalsolinol, in analgesia tests conducted in mice."	( Analgesic effects of 3-carboxysalsolinol alone and in combination with morphine. Blum, K; Hirst, M; Marshall, A, 1977)	0.49
" Neither the control rate of ACh release nor the dose-response curve for atropine were altered by (a) an 8-day morphine injection schedule, and (b) exposure of the tissue to morphine in the bath for 90 min."	( Muscarinic feedback inhibition of acetylcholine release from the myenteric plexus in the quinea pig ileum and its status after chronic exposure to morphine. Jhamandas, K; Sawynok, J, 1977)	0.67
" Compared with basal anesthesia with pentobarbital, 15 mg/kg, neither morphine nor halothane increased sensitivity to any measured effect of propranolol expressed as the slope of the log dose-response relationship."	( Failure of general anesthesia to potentiate propranolol activity. Bragg, DA; Edmonds, CH; Hibbs, CW; Keats, AS; Slogoff, S, 1977)	0.49
" Morphine dose-response curves were determined in the offspring at 5 weeks of age."	( Prenatal administration of morphine to the rat: tolerance to the analgesic effect of morphine in the offspring. Holtzman, SG; O'Callaghan, JP, 1976)	1.46
" The analgesia dose-response curves for the surrogate pairs, nalodeine-nalorphine and codeine-morphine, were parallel but had significantly different slopes."	( A comparative study of the analgesic and respiratory effects of N-allylnorcodeine (nalodeine), nalorphine, codeine and morphine. Elliott, HW; Rundlett Beyer, J, 1976)	0.68
" Dose-response curves were determined for the effects of morphine (0."	( Comparison of the effects of morphine, pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat. Holtzman, SG, 1976)	0.79
" These results emphasize the need to consider not only drug dosage levels, but also the interaction of task difficulty in the application of drugs in learning paradigms."	( Acute effects of morphine and chlorpromazine on the acquisition of shuttle box conditioned avoidance response. Ageel, AM; Chin, L; Jones, BC; Picchioni, AL; Trafton, CL, 1976)	0.6
" Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel."	( Long-acting narcotic antagonist complexes. Gray, AP; Guardina, WJ, 1976)	0.26
" We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar."	( Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists. Arnold, DL; Granchelli, FE; Nelsen, L; Sheth, SG; Sidman, KR; Steber, WD; Strong, P, 1976)	0.26
" There is a more marked tolerance to the depression of stimulating effects, thus the bell shaped dose-response relationship is broadened and shifted somewhat towards higher doses."	( [Relationship between dependence on and tolerance to morphine in the rat (author's transl)]. Fernandes, M; Kluwe, S, 1976)	0.51
" A dose-response study indicated that all values of morphine between 5 and 1000 mug/kg resulted in a transient bradycardia."	( Morphine effects on the cardiovascular system of awake, freely behaving rats. Stein, EA, 1976)	1.95
" The pretreatment of rats by 6-hydroxydopamine strongly potentiated the seizure producing activity of morphine and the dose-response curve of seizure severity shifted to the right."	( Potentiation of morphine-induced seizure by 6-hydroxydopamine. Ayhan, IH, 1976)	0.82
" Possibly, morphine has a diphasic dose-response curve with respect to cardiovascular function and, by inference, on brain noradrenergic mechanisms."	( Effects of morphine on central catecholamine turnover, blood pressure and heart rate in the rat. Gomes, C; Svensson, TH; Trolin, G, 1976)	1.04
" Strength of the conditioned reinforcer, measured in terms of responding on a lever for the stimulus plus infusion of saline solution, was proportional to the unit dosage of morphine employed in pairings of buzzer and drug."	( Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior. Davis, WM; Smith, SG, )	0.32
" Morphine was a potent respiratory depressant at therapeutic dosage while nefopam was not."	( Respiratory effects of nefopam. Bellville, JW; Gasser, JC, 1975)	0.98
" With regard to the dosage and method of administration, ketamine was shown to be less effective than morphine for the first 3 hours postoperatively, but equally effective subsequently, whereas the patients who received ketamine showed a greater progressive tendency for their respiratory parameters to improve with time."	( Intravenous ketamine for postoperative analgesia. Clausen, L; Sinclair, DM; Van Hasselt, CH, 1975)	0.47
" A significant dose-response curve was obtained with nefopam and with morphine, and there was no significant deviation from parallelism."	( Nefopam and morphine in man. Laska, E; Sunshine, A, 1975)	0.87
"Morphine in therapeutic dosage has been shown to impair the plasma 11-hydroxycorticosteroid response to the stress of insulin-induced hypoglycaemia."	( The effects of morphine and nalorphine on the plasma 11-hydroxycorticosteroid response to insulin-induced hypoglycaemia in patients with rheumatoid arthritis. Bell, MA; Buchanan, W; Downie, WW; Nuki, G; Shenkin, A; Wasson, J, 1975)	2.05
" There was a significant difference in the slope of log dose-response curves; these curves were much steeper for pentobarbitone, droperidol and chlorpromazine than for nitrazepam, flunitrazepam, and diazepam."	( [Action of central depressants on the nitrous oxide anesthesia (author's transl)]. Andics, A; Gogolák, G; Huck, S; Stumpf, C, 1975)	0.25
" The rats (drug dependence-experimented rats) who survived the first stage of this experiment were continuously subjected to re-administration by the same dosage schedule as in Exp."	( [Comparison of development of drug dependence in naive and drug dependence-experienced rats]. Tagashira, E; Yanaura, S, 1975)	0.25
"Intraocular pressure (IOP) measurements were made in a series of 92 male surgical patients, to assess the effects of timing and dosage of succinylcholine given after a standardized sleep dose of thiopental (3 mg."	( Thiopental and succinylcholine: Action on intraocular pressure. Bruce, DL; Joshi, C, )	0.13
"Mice were given several atropine injections at a high dosage level."	( Sensitivity changes to morphine and other drugs induced by cholinergic blockade. Contreras, E; Quijada, L; Tamayo, L, 1975)	0.57
" The shift of the morphine dose-response curve to the right is expressed in terms of dose ratios, which were calculated from the ED50 values for morphine obtained 9 days before, and 1, 8, 15, 22 and 29 days after implantation of the polymer."	( Preparation and evaluation of a sustained naloxone delivery system in rats. Fishman, J; Foldes, FF; Hahn, EF; Norton, BI; Ronai, A, 1975)	0.59
" Thus far, the most useful of several dosage forms studied is s suspension in an aluminum monostearate gel."	( Long-acting narcotic antagonist complexes. Gray, AP; Guardina, WJ, 1975)	0.25
" We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar."	( Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists. Arnold, DL; Granchelli, FE; Nelsen, L; Sheth, SG; Sidman, KR; Steber, WD; Strong, P, 1975)	0.25
"Derivatization of the alkaloids cephaeline, codeine, emetine, ephedrine, morphine, narcotine and others with dansyl chloride has been studied with the aim of developing a sensitive and specific liquid chromatographic method for these substances in complex pharmaceutical dosage forms."	( Liquid chromatography of dansyl derivatives of some alkaloids and the application to the analysis of pharmaceuticals. Frei, RW; Santi, W; Thomas, M, 1976)	0.49
" The discriminable ED50 values for both pentazocine and morphine were estimated from dose-response curves and when given in combination (pentazocine ED50 + morphine ED50), more drug-related responding occurred than occurred after either drug (ED50) alone."	( Stimulus properties of the narcotic antagonist pentazocine: similarity to morphine and antagonism by naloxone. Appel, JB; Greenberg, I; Kuhn, DM, 1976)	0.73
" In addition our results suggest that dosage of morphine and morphine blood levels might also modify norepinephrine excretion."	( The effects of morphine and halothane anaesthesia on urine norepinephrine during surgery for congenital heart disease. Lathrop, GD; Liu, WS; Stanley, TH, 1976)	0.86
" The degree of aversion was related to the maintenance dosage of morphine."	( Conditioned flavor aversions for assessing precipitated morphine abstinence in rats. Pilcher, CW; Stolerman, IP, 1976)	0.74
" delta PWL did not vary with morphine, indicating that the dose-response curves were parallel but shifted to the right for the hyperesthetic paw."	( Studies on the spinal interaction of morphine and the NMDA antagonist MK-801 on the hyperesthesia observed in a rat model of sciatic mononeuropathy. Yaksh, TL; Yamamoto, T, 1992)	0.85
" In addition, dose-response curves were determined for (+)- and (-)-phenylmorphan using the mouse tail-flick assay with the (+)-enantiomer found to be about 7 times more potent."	( Phenylmorphans and analogues: opioid receptor subtype selectivity and effect of conformation on activity. Froimowitz, M; Pasternak, GW; Pick, CG, 1992)	0.28
" The shifts in the dose-response curve of the morphine were parallel."	( Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. Stevens, DL; Welch, SP, 1992)	0.76
" A dose-response curve was also made for the mu-opioid receptor agonist, morphine."	( Spinal antinociception by Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr, a selective delta-opioid receptor agonist. Dickenson, AH; Kalso, EA; McQuay, HJ; Sullivan, AF, 1992)	0.52
" 1) In the presence of a fixed dose of DPDPE (150 nmol), there was a left shift in the dose-response curve of the mu agonist, with the magnitude of the shifts being greater than those anticipated from a simple additive interaction: PL017 (31-fold) > or = DAMGO (20-fold) > morphine (6."	( Isobolographic and dose-response analyses of the interaction between intrathecal mu and delta agonists: effects of naltrindole and its benzofuran analog (NTB). Malmberg, AB; Yaksh, TL, 1992)	0.46
" We now report that LiCl pretreatment shifted the antinociceptive dose-response curve produced by the opioid agonists morphine, [D-Ala2, MePhe4, Gly5-ol]enkephalin (DAMGO) and sufentanil in inverse order of their intrinsic efficacy."	( Opioid efficacy is linked to the LiCl-sensitive, inositol-1,4,5-trisphosphate-restorable pathway. Connelly, CD; Martinez, RP; Raffa, RB, 1992)	0.49
" Supraspinal TRIMU-5 also potentiates spinal morphine directly, shifting its dose-response to the left."	( Supraspinal mu 2-opioid receptors mediate spinal/supraspinal morphine synergy. Gacel, G; Pasternak, GW; Pick, CG; Roques, B, 1992)	0.78
" In contrast, morphine (the positive control) produced expected dose-response relationships on measures of reinforcing and physiologic effects."	( Psychoactivity and abuse potential of sumatriptan. Busch, M; Jasinski, DR; Preston, KL; Sullivan, JT; Testa, MP, 1992)	0.64
" agonist dose-response curves by theophylline (i."	( Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. DeLander, GE; Mosberg, HI; Porreca, F, 1992)	0.28
" Experiment 2 demonstrated that the dose-response curve relating systemic morphine treatment to increases in TFR thresholds was shifted to the right in chronic spinal rats."	( Characterization of tailshock elicited withdrawal reflexes in intact and spinal rats. Anderson, ME; Borszcz, GS; Johnson, CP; Young, BJ, 1992)	0.51
" The dextrorphan-trained birds generalized to l-cyclorphan at 10 mg/kg; naltrexone did not alter the l-cyclorphan dose-response curve for this effect."	( Discriminative stimulus effects of cyclorphan: selective antagonism with naltrexone. Bertalmio, AJ; Woods, JH, 1992)	0.28
"6 and 10 mg/kg), resulting in a parallel, rightward shift in the MOR dose-response curve."	( Modulation of morphine antinociception by antagonism of H2 receptors in the periaqueductal gray. Hough, LB; Nalwalk, JW, 1992)	0.64
" Tolerance, assessed on a tail-flick device using dose-response curve (DRC) methodology, developed more rapidly and reached greater magnitude when morphine and the distinctive context were explicitly paired rather than explicitly unpaired."	( Effect of number of conditioning trials on the development of associative tolerance to morphine. Cepeda-Benito, A; Tiffany, ST, 1992)	0.71
" At the 96 h IDI, tolerance, as indexed by shifts in dose-response curves, was controlled primarily by associative processes."	( Contribution of associative and nonassociative processes to the development of morphine tolerance. Cepeda-Benito, A; Drobes, DJ; Tiffany, ST, 1992)	0.51
" However, in rats trained on caffeine, PPA had no effect on the dose-response relationship for caffeine; similarly, in rats trained on PPA, caffeine had no effect on the dose-response relationship for PPA (no synergism or antagonism)."	( Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Mariathasan, EA; Stolerman, IP, 1992)	0.28
"Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness."	( Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use. Chester, MA; Geoghegan, MF; Goodwin, VA; Johnson, NG; Moulin, DE; Murray-Parsons, N, 1992)	0.28
" The patient was treated over a period of 48 days with a morphine dosage ranging from 10 to 60 mg/h, which kept her free of pain."	( [Continuous ambulatory intravenous morphine infusion for pain therapy in advanced ovarian cancer]. Günter, HH; Hilfrich, J; Kühnle, H; Schönborn, I; Sorge, J; Steffmann, B, 1992)	0.81
" The opioid antagonist naloxone and the alpha-2 adrenergic antagonist idazoxan were given as intrathecal pretreatments at doses chosen to shift the dose-response curves of their corresponding agonist (given alone) 4- to 10-fold to the right; this always resulted in a smaller, but significant (2- to 4-fold) shift in the dose-response curve of the other agonist given alone."	( Spinal interactions between opioid and noradrenergic agonists in mice: multiplicativity involves delta and alpha-2 receptors. Hylden, JK; Kitto, K; Lei, S; Roerig, SC; Wilcox, GL, 1992)	0.28
"The present research examined morphine dose-response effects on both the formalin test and on CNS monoamine (MA) levels and the metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hypoalgesic (76) and hyperalgesic (SN) strains of domestic fowl."	( Central monoaminergic changes induced by morphine in hypoalgesic and hyperalgesic strains of domestic fowl. Hoganson, DA; Hughes, RA; Sufka, KJ, 1992)	0.84
" These findings suggest the morphine dosage to be indicative of the progress of the disease rather than of a drug tolerance."	( Dose changes in long- and medium-term intrathecal morphine therapy of cancer pain. Neidhardt, J; Schramm, J; Schultheiss, R, 1992)	0.83
", self-administered less morphine during the nighttime); specifically, dosing declined 48% from the daytime level."	( Patient-controlled analgesia for cancer pain: a long-term study of inpatient and outpatient use. Chen, S; Citron, ML; Hoffman, M; Kalra, JM; Seltzer, VL; Walczak, MB, 1992)	0.59
" Follow-up controls were carried out at least every week and consisted on the evaluation the dosage efficacy, dose adjustments, catheter condition, physical activity, neurologic state, and requirements of adjuvant medication."	( [Experience with the Du Pen epidural catheter in chronic cancer pain]. Aguilar, JL; González-Carrasco, FJ; Montes, A; Roca, G; Vallés, J; Vidal, F, )	0.13
" This method for the study of opioid sensitivity allowed a wide dosage range to be studied."	( Opioid sensitivity of chronic pain: a patient-controlled analgesia method. Carroll, D; Faura, C; Glynn, CJ; Jadad, AR; Liu, Y; McQuay, HJ; Moore, RA, 1992)	0.28
" Dose-response curves for all the drugs tested were similar and a significant dose-dependent antinociceptive action was evident in the formalin and writhing tests."	( Antinociceptive effects of Ca2+ channel blockers. Bustamante, D; Fernandez, E; Kramer, V; Miranda, HF; Paeile, C; Pelissier, T; Pinardi, G; Saavedra, H, 1992)	0.28
" Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects."	( Inhibition of Microlax-induced experimental diarrhoea with narcotic-like extracts of Psidium guajava leaf in rats. Lutterodt, GD, 1992)	0.76
" Dose-response curves were obtained either non-cumulatively with morphine alone or cumulatively with morphine alone and in combination with different concentrations of naloxone."	( Naloxone counteracts the fast development of tolerance to morphine in guinea-pig ileum. Hustveit, O; Oye, I; Setekleiv, J, 1992)	0.77
" The postoperative peridural dosage of 5 mg morphine (three times in 24 h) was very effective."	( [Continuous peridural anesthesia in abdominal surgery. An alternative for elderly patients]. Fuchs, C, 1992)	0.54
" Considered together, the site-localization, pharmacologic blocking, and dose-response data support the hypothesis that specific regions of the mPRF can contribute to the long-recognized ability of morphine to inhibit REM sleep and alter respiratory control."	( Sleep disruption and increased apneas after pontine microinjection of morphine. Baghdoyan, HA; Keifer, JC; Lydic, R, 1992)	0.71
" In contrast, at the low dose of either local anesthetic, after the resolution of the transient motor weakness, these doses resulted in a significant leftward shift in the dose-response curves for intrathecal morphine on both the hot plate and paw pressure, as measured by the maximum observed peak effect and by the area under the time-effect curve."	( Interaction of intrathecal morphine with bupivacaine and lidocaine in the rat. Penning, JP; Yaksh, TL, 1992)	0.77
" Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially."	( Plasma morphine-3-glucuronide, morphine-6-glucuronide and morphine concentrations in patients receiving long-term epidural morphine. Bradley, JP; Brown, AM; Cavenagh, JD; Ravenscroft, PJ; Schneider, JJ, 1992)	0.74
" The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration."	( Effect of morphine and pancuronium on the stress response in ventilated preterm infants. Dean, HG; Levene, MI; Otoo, F; Puntis, JW; Quinn, MW; Rushforth, JA; Wild, J, 1992)	0.69
" Plasma morphine concentrations were more sustained for 7 h after dosage with the MAN suppository, with lower peak (8."	( Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo. Cosolo, W; McCormick, Y; Morgan, DJ; Roller, L; Zalcberg, J, 1992)	1.04
" Dosing periods were separated by a 14-day washout."	( An evaluation of the effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR) after multiple doses. Bass, J; Hulse, J; Lee, JW; Shepard, KV, 1992)	0.51
" Using a cumulative dosing protocol, intravenous administration (0."	( Systemic and microiontophoretic administration of morphine differentially effect ventral pallidum/substantia innominata neuronal activity. Chrobak, JJ; Napier, TC; Yew, J, 1992)	0.54
" Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods."	( A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain. Boureau, F; Brunet, R; d'Arnoux, C; Estève, M; Ranchère, JY; Roquefeuil, B; Roussel, P; Saudubray, F; Siou, DK; Vedrenne, J, 1992)	0.78
"4 mg/ml for morphine and methadone, respectively, were achieved using an ascending dosage schedule."	( Morphine and methadone dependence in the rat: withdrawal and brain met-enkephalin levels. Olley, JE; Pierce, TL; Tiong, GK, 1992)	2.11
" Both responses demonstrated a biphasic dose-response pattern, with depressant effects (hypothermia and hypokinesis) predominant at high doses, and excitatory effects (hyperthermia and hyperkinesis) predominant at low doses."	( Biotelemetric investigation of morphine's thermic and kinetic effects in rats. Dafters, R; Taggart, P, 1992)	0.57
" On day 7, the magnitude of tolerance was assessed by establishing dose-response curves for the effect of the chronic drug given as an intrathecal bolus."	( Studies of morphine and D-ala2-D-leu5-enkephalin (DADLE) cross-tolerance after continuous intrathecal infusion in the rat. Stevens, CW; Yaksh, TL, 1992)	0.67
" Morphine dose-response curves at different temperatures (30, 37 or 40 degrees C) from right atria of the rat were obtained."	( Temperature-dependent effects of morphine on the isolated right atrium. Laorden, ML; Ruiz, F; Valcarcel, MI, 1992)	1.48
" Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects."	( Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Cmielewski, PL; Cousins, MJ; Gourlay, GK; Owen, H; Plummer, JL, 1992)	0.91
" Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease."	( A long-term survey of morphine in cancer pain patients. Grond, S; Jung, H; Meuser, T; Schug, SA; Stobbe, B; Zech, D, 1992)	0.82
" It is also suggested that dibencozide could be useful in clinical practice for reducing the dosage of opioids."	( Depressive effects of mu and delta opioid receptor agonists on activities of dorsal horn neurones are enhanced by dibencozide. Bing, Z; Bouhassira, D; Le Bars, D; Villanueva, L, 1991)	0.28
" catheters, dose-response curves were carried out using the hot plate (HP) test for a number of receptor-preferring opioids."	( Characteristics of dose-dependent antagonism by beta-funaltrexamine of the antinociceptive effects of intrathecal mu agonists. Mjanger, E; Yaksh, TL, 1991)	0.28
") of a 15 mg naltrexone pellet there was a significant shift to the right of the fentanyl dose-response curves for analgesia and lethality."	( Evaluation of receptor mechanism mediating fentanyl analgesia and toxicity. Jang, Y; Yoburn, BC, 1991)	0.28
" The present study was designed to examine in rats the temporal and dosage parameters of naloxone-induced potentiation of morphine analgesia and the effect of continuous infusion of naloxone on the analgesic potency of other mu agonists."	( Increased analgesic potency of mu agonists after continuous naloxone infusion in rats. Holtzman, SG; Paronis, CA, 1991)	0.49
" To test for a specific toxic effect on the neurons of the ciliary ganglion, we generated a dose-response curve for toxicity in vitro and determined that naltrexone was not toxic over concentration ranges that are likely to exist in vivo."	( Endogenous opioids modulate neuronal survival in the developing avian ciliary ganglion. Ford, MJ; Meriney, SD; Oliva, D; Pilar, G, 1991)	0.28
"63 mg/kg), the morphine dose-response curve was shifted progressively in parallel to the right and the maximal effect of morphine was not altered; Schild analysis yielded a slope of close to -1."	( 5-hydroxytryptamine (HT)1A receptors and the tail-flick response. II. High efficacy 5-HT1A agonists attenuate morphine-induced antinociception in mice in a competitive-like manner. Colpaert, FC; Millan, MJ, 1991)	0.85
" In their presence, the morphine dose-response curve was shifted in parallel to the right with no loss of maximal effect."	( 5-hydroxytryptamine (HT)1A receptors and the tail-flick response. III. Structurally diverse 5-HT1A partial agonists attenuate mu- but not kappa-opioid antinociception in mice and rats. Colpaert, FC; Millan, MJ, 1991)	0.59
" Dose-response curves for intrathecally administered agonists with mu- and/or delta-opioid activity were shifted to the left for inflamed hindpaws when compared to contralateral non-inflamed paws."	( Spinal opioid analgesic effects are enhanced in a model of unilateral inflammation/hyperalgesia: possible involvement of noradrenergic mechanisms. Dubner, R; Hylden, JL; Iadarola, MJ; Nahin, RL; Thomas, DA, 1991)	0.28
" Regression analyses failed to reflect significant shifts in the dose-response functions for either agonist on either measure."	( Gender effects and central opioid analgesia. Bodnar, RJ; Kepler, KL; Kest, B; Pasternak, GW; Paul, D; Standifer, KM, 1991)	0.28
"1-810 nmol) caused a rightward shift of dose-response curve and reduction of maximal effect of alpha-2 agonists used."	( Relative efficacy of spinal alpha-2 agonists, dexmedetomidine, clonidine and ST-91, determined in vivo by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, an irreversible antagonist. Takano, Y; Yaksh, TL, 1991)	0.28
" Comparison of the dose-response curves demonstrated a difference in the intensity of the stimulus effects."	( The discriminative stimulus effects of diazepam in rats at two training doses. Franklin, SR; Tang, AH, 1991)	0.28
"25 mg kg-1) caused a shift of the clonidine antisecretory dose-response curve to the right, demonstrating tolerance."	( Studies to determine whether there is tolerance or cross-tolerance to the antisecretory effect of morphine and clonidine in the rat intestine. Bentley, GA; Coupar, IM; Margaritis, J, 1991)	0.5
" The dose-response relationship of morphine-induced suppression of FLI varied in different laminae."	( Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. Basbaum, AI; Levine, JD; Menétrey, D; Presley, RW, 1990)	0.97
" Analgesics administered intermittently were generally effective when given, however, the dosing interval was too long for the agents used resulting in frequent reports of poor pain relief."	( Postoperative pain therapy: a survey of patients' expectations and their experiences. McMillan, V; Owen, H; Rogowski, D, 1990)	0.28
" Upon pretreatment with morphine over greater than or equal to 12 h, a fourfold shift of the PGE1-morphine dose-response curve was observed, whether or not IBMX was added."	( Regulation of cyclic AMP by the mu-opioid receptor in human neuroblastoma SH-SY5Y cells. Duan, DS; Eiger, S; Lameh, J; Sadée, W; Yu, VC, 1990)	0.59
" Extracellular single unit recordings from both wide dynamic range and nociceptive specific neurons during controlled repetitive electrical stimulation of the ipsilateral hind paw indicated that SP enhanced C-evoked firing in an apparent dose-related manner (100 greater than 20 = 4 nmol), whereas DPDT inhibited C-evoked discharges with an apparent bell-shaped dose-response (20 greater than 100 = 4 nmol)."	( Evidence that substance P selectively modulates C-fiber-evoked discharges of dorsal horn nociceptive neurons. Hayes, RL; Kellstein, DE; Mayer, DJ; Price, DD, 1990)	0.28
" On the one hand, the resulting data strongly validate the model since they show that pain and nociceptive reflex are similarly depressed by morphine in a dose-response fashion."	( [Clinical exploration of nociception with the use of reflexologic techniques]. Willer, JC, 1990)	0.48
" Intrathecal lidocaine in the dosage range tested during isobolographic analysis revealed no motor deficits."	( Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat. Gebhart, GF; Maves, TJ, 1992)	0.54
" However, when the epidural morphine was given in a double-blind and placebo-controlled manner, morphine did not produce greater analgesia than placebo and no dose-response relationship was seen."	( Double-blind testing fails to confirm analgesic response to extradural morphine. Glynn, CJ; Jadad, AR; McQuay, HJ; Popat, MT, 1991)	0.81
" The data suggest that this dosage regimen of diamorphine is safe."	( Diamorphine infusion in the preterm neonate. Barrett, DA; Davis, SS; Elias-Jones, AC; Rutter, N; Shaw, PN, 1991)	1.16
" The trial does give an estimation for the starting point of the intrathecal dosage but, as we have demonstrated, this is, at times, at a greater dosage than previously had been predicted."	( Epidural trial in implantation of intrathecal morphine infusion pumps. Adler, RJ; Hupert, C; Krieger, AJ; Maniker, AH, 1991)	0.54
" In this study, we analyzed plasma morphine concentration in cancer patients who received continuous morphine drip and/or oral administrations of morphine: (1) The plasma concentration of morphine varied widely in patients whose pain was satisfactorily controlled at a constant dosage of morphine."	( Relationship between plasma concentration of morphine and analgesic effectiveness. Hiraga, K; Konishi, M; Oguma, T; Yokokawa, N, 1991)	0.82
" The level of analgesia provided during the early post-dosing period, at the end of the dosing period and overall over the twelve hour interval were also equivalent between the preparations."	( Morphine at gramme doses: kinetics, dynamics and clinical need. Court, M; McKellar, J; Miller, AJ; Smith, KJ, 1991)	1.72
" There was a wide dosage range and the dose required appears independent of pathology, age of patient or previous analgesic exposure."	( Morphine sulphate tablets in hospice practice. Bonifant, JD; Clark-Reynolds, M, 1991)	1.72
" This clinical survey showed that the total effectiveness was 92% and that 90% of the patients could experience control of pain with a daily dosage of 240 mg or less of MS Contin."	( A clinical survey of controlled-release morphine sulphate for cancer pain relief in a Japanese hospice. Hayashi, A; Kashiwagi, T; Miyazaki, M; Tsuneto, S, 1991)	0.55
" Acquisition costs for controlled-release morphine tablets, morphine sulphate solution and ancillary materials required for dosing were those actually paid by the hospital pharmacy at the time of the study."	( Cost considerations of analgesic therapy: an analysis of the effects of dosing frequency and route of administration. Goughnour, BR, 1991)	0.55
" The indication for administering MS Contin is not a poor prognosis, but rather pain requiring repeated dosing with potent opioids over periods of more than a few days."	( Guidelines for the use of MS Contin tablets in the management of cancer pain. Warfield, CA, 1991)	0.28
" To understand better the relationship between morphine and M-6-G in cancer patients receiving chronic therapy, we employed high performance liquid chromatography with electrochemical detection to measure: (1) morphine and M-6-G plasma concentrations following discontinuation of dosing in 2 patients, one receiving oral therapy and the other an intravenous infusion; (2) morphine and M-6-G concentrations in random blood samples taken at apparent steady state from 8 patients, 7 with normal renal function and 1 with mild renal insufficiency, who were receiving continuous morphine infusions; and (3) morphine and M-6-G concentrations in random blood samples taken over a period of weeks from 4 patients, 2 with stable and 2 with declining renal function."	( Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady-state concentrations and the consequences of renal failure. Adelhardt, J; Cerbone, DF; Foley, KM; Inturrisi, CE; Khan, E; Layman, M; Portenoy, RK; Stulman, J, 1991)	0.99
" The dosing interval was 5 min, until the patient did not want any further analgesics."	( Intravenous morphine and oxycodone for pain after abdominal surgery. Kalso, E; Linko, K; Onnela, P; Pöyhiä, R; Tammisto, T; Tigerstedt, I, 1991)	0.66
" Concurrent dosing of pentazocine (2 mg/kg, IP) and tripelennamine (2."	( Potentiation of pentazocine conditioned place preference by tripelennamine in rats. Masukawa, Y; Misawa, M; Shiozaki, Y; Suzuki, T, 1991)	0.28
" In dose-response studies, beta-FNA antagonized all the actions with similar potencies (ID50 values of 12."	( Comparison of naloxonazine and beta-funaltrexamine antagonism of mu 1 and mu 2 opioid actions. Pasternak, GW; Paul, D; Pick, CG, 1991)	0.28
" If these results are confirmed in a large group of patients, the controlled-release morphine sulphate tablets may offer a convenient (less frequent) dosing compared with regular tablets in children suffering from chronic pain due to malignancy."	( Plasma concentrations of morphine in children with chronic pain--comparison of controlled release and regular morphine sulphate tablets. Nahata, MC, 1991)	0.81
" After the first eight patients, dosage regimens were changed and satisfactory postoperative analgesia was obtained in the last 20 patients with few side-effects."	( [Patient-controlled analgesia in children]. Dubois, MC; Estève, C; Murat, I; Saint-Maurice, C, 1991)	0.28
" The results suggest that the currently used dosing regimen of diamorphine achieves a safe and effective morphine concentration in the premature newborn but that the loading dose could be modified to achieve a more rapid onset of analgesia."	( Morphine kinetics after diamorphine infusion in premature neonates. Barrett, DA; Davis, SS; Elias-Jones, AC; Rutter, N; Shaw, PN, 1991)	1.96
" During an eight-month period, 161 women undergoing cesarean delivery were assigned to receive narcotics by either epidural morphine (76 patients) or patient-controlled analgesia (85 patients) using a combined continuous infusion and demand dosing of meperidine."	( Comparison of patient-controlled analgesia and epidural morphine for postcesarean pain and recovery. Karaiskakis, PT; Morton, RD; Norvell, MJ; Rayburn, WF; Smith, CV, 1991)	0.73
" Comparison of the dose-response curves (i."	( Antinociceptive synergism between supraspinal and spinal sites after subcutaneous morphine evidenced by CNS morphine content. Kishioka, S; Kitabata, Y; Miyamoto, Y; Morita, N; Ozaki, M; Yamamoto, H; Yamanishi, T, 1991)	0.51
" Antinociception, tested by the tail-flick method, did not diminish over days 5-8, yet on day 9 a rightward shift in the dose-response curve occurred."	( Evidence for opiate tolerance in newborn rats. Frenk, H; Van Praag, H, 1991)	0.28
" These experiments determined specifically morphine's effects on the distinctiveness and time course of stimulus representations by examining morphine's dose-response effect on (a) differential responding to A and B and their conditional control over responding to X within the compounds and (b) the unconditioned excitatory effects of the compounds and their components as assessed by their ability to modify the amplitude of the unconditioned NMR."	( Morphine's effects on differential serial compound conditioning and reflex modification of the rabbit's (Oryctolagus cuniculus) nictitating membrane response. Gormezano, I; McEchron, MD, 1991)	1.99
" Drug interactions were studied by redetermining the cocaine dose-response curve in the presence of various fixed doses of the other drugs."	( The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon. Evans, EB; Wenger, GR, 1990)	0.28
"The purpose of this study was to determine the effect of oral estazolam at two and three times the usually recommended dosage (2 mg) on ventilation and respiratory drive during wakefulness."	( Ventilatory response to single, high dose estazolam in healthy humans. Badr, S; Begle, RL; Juan, D; Skatrud, JB, 1990)	0.28
" Dose-response curves for IT morphine were obtained in the presence of fixed doses (0."	( Interaction of intrathecal morphine and ST-91 on antinociception in the rat: dose-response analysis, antagonism and clearance. Monasky, MS; Stevens, CW; Yaksh, TL; Zinsmeister, AR, 1990)	0.87
" On day 7, the magnitude of tolerance was assessed in each group by establishing intrathecal dose-response curves and ED50 values for sufentanil and morphine given as a bolus injection."	( Differential cross-tolerance between intrathecal morphine and sufentanil in the rat. Sosnowski, M; Yaksh, TL, 1990)	0.73
" The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve."	( Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy. Bagley, J; Harris, S; Lin, BS; Lloyd, P; Messineo, E; Ossipov, MH, 1990)	0.28
"The benefits of two dosing methods, patient-controlled analgesia (PCA) with morphine sulfate (MS) alone and PCA plus continuous infusion of morphine sulfate (PCA + CI) were clinically evaluated in a randomized, single-blinded study of 30 adult abdominal surgery patients."	( Evaluation of patient-controlled analgesia (PCA) versus PCA plus continuous infusion in postoperative cancer patients. Hansen, LA; Lehman, ME; Noyes, MA, 1991)	0.51
"In an attempt to maintain stable levels of an alpha 2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery."	( Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period. Duncan, SR; Jarvis, DJ; Maze, M; Segal, IS; White, PF, 1991)	0.28
" The efficacy of the treatment was estimated from: 1) daily dosage (intraspinal and total opiates, and intraspinal bupivacaine), and 2) scores of non-opiate analgesic and sedative consumption, gait and daily activities, and amount and pattern of sleep."	( Long-term intrathecal morphine and bupivacaine in "refractory" cancer pain. I. Results from the first series of 52 patients. Appelgren, L; Curelaru, I; Einarsson, S; Hultman, E; Linder, LE; Nitescu, P; Sjöberg, M, 1991)	0.6
" Among the patients receiving the bolus injections, morphine was required 62 +/- 15 (SEM) times over the 24-h study period with total morphine dosage averaging 30 +/- 15 mg."	( Continuous infusion of interpleural bupivacaine maintains effective analgesia after cholecystectomy. Citron, GM; Kirz, LI; Laurito, CE; Pelligrino, DA; Riegler, FX; Segil, LJ; VadeBoncouer, TR, 1991)	0.53
" The use of IT morphine significantly reduced the dosage requirement of epidural bupivacaine."	( Intrathecal morphine 0.2 mg versus epidural bupivacaine 0.125% or their combination: effects on parturients. Abouleish, E; Lorenz, T; Rashad, MN; Rawal, N; Shaw, J, 1991)	1.01
" Tolerance was indexed as the magnitude of the shift to the right of the dose-response curve (DRC)."	( Effect of interdose interval on the development of associative tolerance to morphine in the rat: a dose-response analysis. Drobes, DJ; Maude-Griffin, PM; Tiffany, ST, 1991)	0.51
" Subjective, behavioral and miotic changes were assessed prior to dosing and intermittently for 12 h after drug administration."	( Abuse potential and pharmacological comparison of tramadol and morphine. Jasinski, DR; Preston, KL; Testa, M, 1991)	0.52
" With the dosage regimens used, neither drug adequately controlled moderate to severe pain in the immediate postoperative period."	( Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate postoperative pain. Fragen, RJ; Peirce, RJ; Pemberton, DM, 1990)	0.54
" Seventy patients completed this multi-investigator study; each patient was assigned to one of two dosing protocols, as determined by their previous analgesic regimen."	( A multi-investigator clinical evaluation of oral controlled-release morphine (MS Contin tablets) administered to cancer patients. Fitzmartin, RD; Goldenheim, PD; Lazarus, H, 1990)	0.51
" ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH."	( Effect of acetylcholine and morphine on bronchial smooth muscle contraction and its modulation by steroid hormones. Kadir, BA; Khalid, BA; Morat, PB; Nabishah, BM, 1990)	0.57
" Although the relationship between these different effects is not known, the similarity in their dose-response relationship suggests that they may be mediated by a common mechanism."	( Aversive properties of bombesin in rats. Lorens, SA; Meisenberg, G; Simmons, WH, 1990)	0.28
" On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0."	( Drug interactions in the reinforcing effects of over-the-counter cough syrups. Masukawa, Y; Misawa, M; Suzuki, T, 1990)	0.28
" Dose-response studies demonstrated that higher doses (greater than 1 microgram) of morphine IC were required to block TRH-induced increases in preweaning rats."	( Morphine inhibits TRH-induced intestinal transit increases. Bond, EF; Heitkemper, MM, )	1.8
" Although the average opioid dosage requirements were 10 to 28% higher with SQ-PCA, it is an acceptable alternative to conventional IV-PCA for pain control after major surgical procedures."	( Subcutaneous-PCA: an alternative to IV-PCA for postoperative pain management. White, PF, 1990)	0.28
" In Long-Evans rats, BW942C produced a biphasic dose-response curve for urine output with lower doses increasing and higher doses suppressing output."	( Kappa opioid partial agonist activity of the enkephalin-like pentapeptide BW942C based on urination and in vitro studies in humans and animals. Cone, EJ; Johnson, RE; Su, TP; Vaupel, DB, 1990)	0.28
" An inactive dose of intrathecally-administered midazolam (20 micrograms) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests."	( Interaction of midazolam and morphine in the spinal cord of the rat. Sabbe, MB; Stevens, CW; Yaksh, TL; Yanez, A, 1990)	0.77
" On day 6, the magnitude of tolerance was assessed by establishing IT dose-response lines for the effect of the chronic drug given as bolus injections (probe)."	( Tolerance to delta- but not mu-opioid receptors in the spinal cord attenuates inhibition of the tail-flick response induced by beta-endorphin administered intracerebroventricularly in mice. Suh, HH; Tseng, LF, 1990)	0.28
" Proglumide both shifted the dose-response curve for morphine analgesia to the left and prolonged morphine's duration of action."	( Proglumide selectively potentiates supraspinal mu 1 opioid analgesia in mice. Bodnar, RJ; Pasternak, GW; Paul, D, 1990)	0.53
" morphine dose-response line was shown to be displaced progressively to the right with decreasing maximal effect (i."	( Modulation of the potency and efficacy of mu-mediated antinociception by delta agonists in the mouse. Mosberg, HI; Porreca, F; Qi, JN, 1990)	1.19
") had no effects on duodenal intraluminal pressure, but reduced the responses to distension with a bell-shaped dose-response relationship."	( The effects of granisetron, ICS 205-930 and ondansetron on the visceral pain reflex induced by duodenal distension. Moss, HE; Sanger, GJ, 1990)	0.28
" The extent to which this phenomenon depends upon the dosage employed has not been elucidated."	( [Urinary retention in connection with postoperative pain treatment with epidural opioids]. Andersen, JT; Hansen, BJ; Rosenberg, J, 1990)	0.28
" Morphine dose-response relationships were fitted to a 4 parameter sigmoidal function."	( Behavioural modification of bulbospinal serotonergic inhibition and morphine analgesia. Gamble, GD; Milne, RJ, 1990)	1.42
" The described approach made it possible to reduce substantially the dosage and to protract the action of morphine, as compared with intramuscular administration."	( [Administration of morphine into the cerebral ventricles in chronic intractable pain]. Houdek, M; Opavský, J, 1990)	0.82
" The average nursing time for narcotic dosing with the standard policy was 5 minutes/unit dose."	( Alternative delivery system for controlled drugs in the surgical intensive care unit. Dyke, C; Martin, RL; Weigelt, JA, 1990)	0.28
" Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED50 calculated."	( Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis. Green, J; Harris, S; Lloyd, P; Lozito, R; Messineo, E; Ossipov, MH, 1990)	0.53
" administration of verapamil (30-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) significantly enhanced, in a dose-dependent way, the analgesic effects of morphine and produced a parallel displacement to the left of the morphine log dose-response line."	( Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test. Baeyens, JM; Del Pozo, E; Ruiz-García, C, 1990)	0.47
" The quantitative significance of the active metabolite morphine-6-glucuronide was assessed, and the effects of novel dosing forms on morphine metabolism and distribution were examined."	( Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Joel, S; Osborne, R; Slevin, M; Trew, D, 1990)	1.97
" Tolerance did not develop in the PCA group; in patients receiving continuous infusion morphine dosage continued to increase throughout the study while pain scores remained constant, indicating that tolerance had developed."	( Self-administration of morphine in bone marrow transplant patients reduces drug requirement. Benedetti, C; Chapman, RC; Hill, HF; Kornell, JA; Saeger, LC; Sullivan, KM, 1990)	0.81
" These findings call for cautious dosing of oral and intravenous morphine in patients with severe end stage liver disease."	( The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Eriksson, S; Hasselström, J; Persson, A; Rane, A; Säwe, J; Svensson, JO, 1990)	0.79
" Cases where the dosage of MDP would be influenced by neurological, hemodynamic, or painful diagnoses were excluded."	( Age-related differences in the use of morphine, diazepam, and pancuronium for mechanically ventilated children. Albert, MA; Lucking, SE; Mickell, JJ; Pedigo, SA, 1990)	0.55
" The mean dosing interval was 15 hr and no episodes of nausea, vomiting, hypotension or histamine release were noted."	( Lumbar and thoracic epidural analgesia via the caudal approach for postoperative pain relief in infants and children. Gurkowski, MA; Pollard, TG; Rasch, DK; Webster, DE, 1990)	0.28
" When doses of morphine which had no significant effect when administered alone (1 or 3 mg/kg) were combined with cocaine, the cocaine dose-response curve for efficiency was shifted down and to the left and response rates were increased."	( Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats. Wenger, GR; Wright, DW, 1990)	0.86
" morphine dose-response line."	( Modulation of morphine antinociception by peripheral [Leu5]enkephalin: a synergistic interaction. Jiang, Q; Porreca, F; Tallarida, RJ, 1990)	1.55
" There was a strong dose-response relationship between feeding frequency and a decreased incidence of significant hyperbilirubinemia (transcutaneous bilirubin readings greater than or equal to 23."	( Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Yamanouchi, I; Yamauchi, Y, 1990)	0.28
", consistently produced a nearly maximal hypothermic response in non tolerant rats, whereas this dosage induced an elevation of body temperature in tolerant rats."	( Modification of rat thermal responses to morphine by alpha-FMH suggests a role for neural histamine in morphine tolerance. Arrigo-Reina, R; Spadaro, C, 1990)	0.54
" Dose-response curves were determined with a probit procedure."	( Sedative and hypnotic midazolam-morphine interactions in rats. Bradley, EL; Brown, PT; Kissin, I, 1990)	0.56
" In both species, bell-shaped dose-response curves were obtained, indicating that high doses of gentamicin had little or no effect."	( Antinociception induced by intraperitoneal injection of gentamicin in rats and mice. Corrado, AP; Prado, WA; Rego, EM; Tonussi, CR, 1990)	0.28
" Dose-response functions for generalization of morphine stimulus control were determined before, during, and after repeated treatment with selected doses of morphine."	( Tolerance to morphine stimulus control: role of morphine maintenance dose. Doty, MD; Lipinski, WJ; Sannerud, CA; Steigerwald, ES; Tetrick, LE; Young, AM, 1990)	0.91
" The return to normal naltrexone sensitivity after elimination of the two highest doses suggests that a reliable association between the lower and higher doses in a cumulative dosing procedure can result in conditioned effects to the lower doses."	( Enhanced sensitivity to behavioral effects of naltrexone in rats. Goldberg, SR; Katz, JL; Schindler, CW; Su, TP; Wu, XZ, 1990)	0.28
" Mathematic analysis of the dose-response (wheal) relationship suggested that two different effects were involved."	( Morphine-induced skin wheals: a possible model for the study of histamine release. Erill, S; Saucedo, R, 1985)	1.71
" CI was always preceded by a period of repetitive dosing of opioids."	( I.v. infusion of opioids for cancer pain: clinical review and guidelines for use. Foley, KM; Inturrisi, CE; Moulin, DE; Portenoy, RK; Rogers, A, 1986)	0.27
" The mean efficient dosage is 3 mg of morphine chlorhydrate once or twice a day."	( [Intrathecal injection of morphine in the ambulatory treatment of neoplastic pain (lumbar route)]. Esteve, M; Guillaume, A; Vedrenne, JB, 1986)	0.84
" The study design included an attempt at conversion of 30 patients from the previously required narcotic analgesic to around the clock (ATC) 4-h dosing of morphine sulfate immediate-release (MSIR) that would provide satisfactory analgesia."	( Dosage range study of morphine sulfate controlled-release. Homesley, HD; Muss, HB; Richards, F; Welander, CE, 1986)	0.78
" On reduction of opioid dosage he had visual and auditory hallucinations and showed deterioration of consciousness progressing to coma."	( Unusual opioid withdrawal syndrome. A case-report. Grochow, LB; Hausheer, F; Kumor, KM, 1987)	0.27
" The naltrexone stimulus-generalization curve and dose-response curve for loss of body weight were shifted to the left by IBMX and Ro 20-1724, which produce quasi-withdrawal, but not by papaverine, which does not."	( Phosphodiesterase inhibitors potentiate opiate-antagonist discrimination by morphine-dependent rats. Holtzman, SG, 1989)	0.51
" Dosing intervals, pain intensity assessments and toxicity were evaluated."	( Does intravenous methadone provide longer lasting analgesia than intravenous morphine? A randomized, double-blind study. Enterline, J; Green, L; Grochow, L; Grossman, S; Sheidler, V, 1989)	0.51
" In 5-min extinction tests with nicotine, rats maintained under the FR schedule yielded a clear dose-response curve with a bar-selection (quantal) index; in these rats, discrimination of nicotine appeared generally poor, and dose-response curves were shallow, when the percentage of drug-appropriate responding (quantitative index) was calculated."	( Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Stolerman, IP, 1989)	0.28
" dose-response curves for the effect of the chronic drug given as a bolus."	( Potency of infused spinal antinociceptive agents is inversely related to magnitude of tolerance after continuous infusion. Stevens, CW; Yaksh, TL, 1989)	0.28
" Dose-response curves were constructed for the opioid effects on C fibre evoked activity of dorsal horn nociceptive neurones following intrathecal application of each opioid, and the ED50 values were correlated with lipid solubility."	( Intrathecal opioids, potency and lipophilicity. Dickenson, AH; McQuay, HJ; Smallman, K; Sullivan, AF, 1989)	0.28
" Antinociception was determined by observing the response to a clamp applied to the tail (Haffner test) in mice and by the tail-flick test in rats; log dose-response curves for antinociception were generated for morphine, clonidine, and each drug combination."	( Antinociceptive interactions between alpha 2-adrenergic and opiate agonists at the spinal level in rodents. Ossipov, MH; Spaulding, TC; Suarez, LJ, 1989)	0.46
"A dose-response analysis of the effects of morphine on fetal heart rate (FHR) and blood pressure (FBP) was conducted in 28 chronically instrumented fetal lambs."	( Morphine-induced tachycardia in fetal lambs: a bell-shaped dose-response curve. Szeto, HH; Zhu, YS, 1989)	1.98
" Both the morphine and normorphine dose-response lines were displaced to the left in the presence of DPDPE."	( Modulation of mu-mediated antinociception by delta agonists in the mouse: selective potentiation of morphine and normorphine by [D-Pen2,D-Pen5]enkephalin. Haaseth, RC; Heyman, JS; Mosberg, HI; Porreca, F; Vaught, JL, 1989)	0.9
" Naloxonazine shifted the supraspinal DAGO dose-response curve 4-fold to the right without changing the curve for spinal DAGO."	( Different mu receptor subtypes mediate spinal and supraspinal analgesia in mice. Bodnar, RJ; Gistrak, MA; Pasternak, GW; Paul, D, 1989)	0.28
" The log dose-response relationship of the infusion rate to peak tailflick latency was linear from 10 to 50 micrograms/kg/min."	( Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model. Ling, GS; Pasternak, GW; Paul, D; Simantov, R, 1989)	0.48
" However, in mice tested with the naltrexone pellets still implanted, the 15 mg naltrexone pellet was able to shift the dose-response function for morphine analgesia more than 300-fold."	( Chronic opioid antagonist treatment: assessment of receptor upregulation. Lutfy, K; Sierra, V; Yoburn, BC, 1989)	0.48
"5 to both morphine and methadone, and their dose-response curves were parallel."	( Differences in efficacies between morphine and methadone demonstrated in the guinea pig ileum: a possible explanation for previous observations on incomplete opioid cross-tolerance. Ivarsson, M; Neil, A, 1989)	0.96
", DPDPE displaced the morphine dose-response line to the left and also potentiated the effects of normorphine and etorphine."	( Differential modulation by [D-Pen2, D-Pen5]enkephalin and dynorphin A-(1-17) of the inhibitory bladder motility effects of selected mu agonists in vivo. Nunan, L; Porreca, F; Sheldon, RJ, 1989)	0.59
" In 11 patients, the dosage of MS Contin was decreased."	( The rectal administration of MS Contin: clinical implications of use in end stage cancer. Bockenstette, J; Kesner, RK; Klein, G; Maloney, CM, )	0.13
" The useful dosage of morphine, the scores of relief, and the frequency of side effects are comparable to those observed in non-geriatric groups."	( The treatment of pain in the elderly patient. The use of oral morphine in the treatment of pain. Rapin, CH, 1989)	0.83
" Experiments 3 and 4 provide data to demonstrate (a) that a positive CPP can be established in our chambers using injections of morphine, (b) that a regimen of dosing with unequal numbers of days of putative and alternate conditioning is a reliable and conservative test of the opioid's ability to establish a CPP, and (c) that although the activity of rats decreases across a session, the general activity of rats before and after conditioning procedures is the same."	( Measuring morphine's capacity to establish a place preference. Hubbell, CL; Marglin, SH; Mattie, ME; Reid, LD, 1989)	0.88
" Neither chronic morphine nor saline pretreatment altered the dose-response function to intrathecal morphine."	( The synergistic effect of concurrent spinal and supraspinal opiate agonisms is reduced by both nociceptive and morphine pretreatment. Advokat, C; Siuciak, JA, 1989)	0.83
" The present study evaluated the roles of gender, gonadectomy and estrous phase upon dose-response and time-response functions of analgesia following intracerebroventricular administration of morphine as measured by the tail-flick and jump tests."	( Roles of gender, gonadectomy and estrous phase in the analgesic effects of intracerebroventricular morphine in rats. Bodnar, RJ; Cooper, ML; Kepler, KL; Kest, B; Kiefel, JM, 1989)	0.68
" After titration of the morphine dosage to optimize the analgesic effect, each patient received 10 days of therapy with either MSC or MSS, then 10 days of therapy with an equal daily dose of the other formulation."	( Control of severe pain with sustained-release morphine tablets v. oral morphine solution. Arkinstall, WW; Goughnour, BR; Stewart, JH; White, JA, 1989)	0.84
" Proposed are ten principles of dosing oral morphine, especially MSC, which were followed in a clinical trial involving cancer patients."	( Principles of cancer pain management. Use of long-acting oral morphine. Blumenreich, M; Brooks, I; De Jager, R; George, E; Savarese, JJ, 1989)	0.78
" In contrast, the reference NSAIDS (piroxicam, indomethacin, naproxen and ibuprofen) exhibited similar dose-response relationships for the analgesic, anti-inflammatory and gastric irritant effects."	( Pemedolac: a novel and long-acting non-narcotic analgesic. Chau, TT; Weichman, BM, 1989)	0.28
" When given on a 12-hourly basis in individually titrated doses, the MSC provided therapeutic plasma morphine concentrations throughout the dosing interval."	( Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients. Besner, JG; Boos, GJ; Maroun, JA; Mount, BM; Sloan, PA; Stewart, JH; Thirlwell, MP, 1989)	0.75
"Fifty-one cancer pain patients with limited opioid exposure participated in a randomized, double-blind, repeated-dose, parallel-group comparison of two dosage strengths of the controlled-release morphine preparation, MS Contin tablets (The Purdue Frederick Company, Norwalk, CT)."	( Oral controlled-release morphine sulfate. Analgesic efficacy and side effects of a 100-mg tablet in cancer pain patients. Fitzmartin, R; Kaiko, RF; Kanner, R; Maldonado, M; Portenoy, RK, 1989)	0.77
" The results showed that MSC 15-mg, 30-mg, 60-mg, and 100-mg dosage strengths are bioequivalent and dose proportional, and, therefore, therapeutically interchangeable."	( The United States experience with oral controlled-release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15-mg, 30-mg, 60-mg, and 100-mg tablet strengths in normal subjects. Goldenheim, PD; Grandy, RP; Horodniak, J; Ingber, E; Kaiko, RF; Oshlack, B; Pav, J; Thomas, G, 1989)	0.52
" Each patient received MSC every 12 hours in accordance with specific dosing procedures designed to arrive at doses that would provide acceptable analgesia without unacceptable side effects."	( Evaluation of dosing guidelines for the use of oral controlled-release morphine (MS Contin tablets). Warfield, CA, 1989)	0.51
" In spite of this difference in the analgesic dosage requirement, the side effect profile was similar for the 2 groups."	( Epidural patient-controlled analgesia (PCA): an alternative to continuous epidural infusions. Engstrom, R; Marlowe, S; White, PF, 1989)	0.28
" The main advantages were not only continuous pain relief despite the fact that the nonepidural control group required more than twice the dosage of morphine derivatives; also, the respiratory and pain-related recovery time was reduced."	( [Catheter epidural analgesia in serial rib fractures]. Glatzl, A; Poigenfürst, J; Sandtner, W; Thonke, N, 1989)	0.48
" Dose-response relationships were modeled with the empirical function; E = Eo + (EMAX*DN)/(ED50N + DN) where E is the time-integrated response, EMAX is the response attributable to morphine, Eo is the baseline response, D is the dose and N is a steepness parameter."	( Behavioural tolerance to morphine analgesia is supraspinally mediated: a quantitative analysis of dose-response relationships. Gamble, GD; Holford, NH; Milne, RJ, 1989)	0.77
" Antinociceptive dose-response curves were constructed for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO; morphine) and delta ([D-Pen2,D-Pen5]enkephalin, DPDPE)-agonists in the absence, and in the presence of the mu non-surmountable antagonist, beta-funaltrexamine (beta-FNA) or the delta-antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is alpha-amino-isobutyric acid)."	( Opioid delta-receptor involvement in supraspinal and spinal antinociception in mice. Heyman, JS; Mosberg, HI; Mulvaney, SA; Porreca, F, 1987)	0.49
" Following intravenous administration PD117302, U50488, U69593 and morphine produced steep parallel dose-response curves indicating antinociceptive activity when evaluated in the paw pressure test."	( kappa-Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat. Hill, RG; Hughes, J; Leighton, GE; Rodriguez, RE, 1988)	0.51
" In an effort to examine the receptor subtypes responsible for opioid analgesia in specific brain regions, we examined dose-response relationships and naloxonazine sensitivity of morphine and two enkephalin derivatives in the above 4 brain regions."	( Role of mu 1-opiate receptors in supraspinal opiate analgesia: a microinjection study. Bodnar, RJ; Lee, SJ; Pasternak, GW; Williams, CL, 1988)	0.47
" Acute exposure to endogenous opioids induces analgesia in the short-term yet shifts the morphine dose-response curve to the right for a period of several weeks."	( ACTH: a single pretreatment enhances the analgesic efficacy of and prevents the development of tolerance to morphine. Hendrie, CA, 1988)	0.71
" 3) The phenomenon was specific since the dose-response curve of the adenosine-inhibitory effect was comparable in preparations from tolerant animals and controls."	( Decreased response to GABA-B agonists in longitudinal smooth muscle-myenteric plexus preparations from morphine-tolerant guinea-pigs. Ciuffi, M; Franchi-Micheli, S; Gentilini, G; Gori, AM; Luzzi, S; Zilletti, L, 1988)	0.49
" After 1 week of treatment and after pump removal, dose-response curves for the induction of antinociception by morphine against noxious heat, pressure and electrical stimulation were shifted to the left across the entire time course of action: this supersensitivity subsided over a period of 1 week postremoval."	( Antagonist-induced opioid receptor up-regulation. I. Characterization of supersensitivity to selective mu and kappa agonists. Herz, A; Millan, MJ; Morris, BJ, 1988)	0.49
" During thermal pain stimulation pymadine had the analgesic effect only at dosage of 5 mg/kg and potentiated the action of morphine given in doses of 3 and 5 mg/kg."	( [Analgesic activity of pymadine]. Bantutova, I; Mitsov, V, )	0.34
" Then increased and repetitive injections of morphine sulphate were administered intracerebroventricularly (ICV) in dosage of 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter, 75 micrograms/5 microliter, 90 micrograms/6 microliter and 105 micrograms/7 microliter on each following day respectively."	( Effect of chronic intracerebroventricular morphine to feeding responses in male rats. Dhatt, RK; Mangat, HK; Rattan, AK, 1988)	0.8
" Physicians often fail to tailor analgesic dosages to the needs of the individual and unnecessarily limit the dosage because they have an ill founded fear that the patient will become addicted."	( Drug management of pain in cancer patients. Tuttle, CB, 1985)	0.27
" There is an inverse dose-response relation for PMN but not PMO."	( Opioid peptides rapidly stimulate superoxide production by human polymorphonuclear leukocytes and macrophages. Gekker, G; Keane, WF; Peterson, PK; Sharp, BM; Suh, HJ; Tsukayama, D, 1985)	0.27
" However, the dose-response curve for naltrexone was not parallel to the morphine or fentanyl dose-response curves."	( An analysis of naltrexone and naloxone's possible agonistic actions in the dog. Martin, WR; Wettstein, JG, 1985)	0.5
" After 10 days, dose-response curves for tail-flick inhibition were determined for both intraperitoneal and intraventricular injections of morphine."	( Intrathecal DSP4 selectively depletes spinal noradrenaline and attenuates morphine analgesia. Ji, XQ; Tsou, K; Zhong, FX, 1985)	0.7
" The dose-response curves were monotonic and the slopes were log-linear."	( Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: a pharmacologic and pathologic study. Durant, PA; Yaksh, TL, 1986)	0.55
" The slopes of the monotonic dose-response curves for the five opioids did not differ significantly."	( Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat. Durant, PA; Noueihed, RY; Yaksh, TL, 1986)	0.48
" (+/-)-Propranolol caused rightward shifts, usually parallel, of the dose-response curves for (-)-isoprenaline."	( The antinociceptive action of some beta-adrenoceptor agonists in mice. Bentley, GA; Starr, J, 1986)	0.27
" All three antihistaminics, at some dosage levels, slightly increased activity when given alone, but strongly enhanced morphine-induced hyperactivity."	( Enhancement of morphine-induced hyperactivity by antihistaminic drugs in mice. Castellano, C; D'Amato, FR; Sansone, M, 1986)	0.83
" Flunitrazepam, Midazolam or Lormetazepam in a higher dosage could be expected."	( [Effect and side effects of oral morphine, lormetazepam and placebos as premedication]. Hartung, M; Hettenbach, A; Krug, C; Tolksdorf, W, 1987)	0.55
" With repeated oral administration it becomes very effective and it may be that on repeated dosage active metabolites, particularly morphine-6-glucuronide, account for much of the analgesic activity."	( Explanation for potency of repeated oral doses of morphine? Aherne, GW; Hanks, GW; Hoskin, PJ; Poulain, P; Turner, P, 1987)	0.73
" dose of morphine, show a dose-dependent rightward shift in hot-plate dose-response curves."	( Spinal infusion of opiate and alpha-2 agonists in rats: tolerance and cross-tolerance studies. Monasky, MS; Stevens, CW; Yaksh, TL, 1988)	0.69
" All three antihistaminics, at some dosage levels, enhanced morphine-induced hyperactivity, but did not change or even reduce locomotor stimulation induced by amphetamine and scopolamine."	( Antihistaminics enhance morphine-, but not amphetamine- and scopolamine-induced hyperactivity in mice. D'Udine, B; Renzi, P; Sansone, M; Vetulani, J, 1987)	0.82
" However, the dosage employed here was associated with urinary and emetic side-effects."	( Efficacy of 0.3 mg morphine intrathecally in preventing tourniquet pain during spinal anaesthesia with hyperbaric bupivacaine. Kalso, E; Rosenberg, PH; Tuominen, M; Valli, H, 1988)	0.6
" Dose-response curves for the relatively specific ligands for the mu-, kappa-, and sigma-receptors were determined using morphine (mu-receptors), dynorphin-(1-13) (kappa-receptors), and N-allylnormetazocine (sigma-receptors)."	( Sites of action of mu-, kappa- and sigma-opiate receptor agonists at the feline ileocecal sphincter. Cohen, S; Ouyang, A; Vos, P, 1988)	0.48
" Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right."	( Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. Arjune, D; Bodnar, RJ; Hahn, EF; Mann, PE; Pasternak, GW; Romero, MT, 1988)	0.55
" Thus, the dose-response curves for fentanyl and sufentanil were shifted to the left and the ED50 of the analgesics lowered in droperidol pre-treated animals."	( Droperidol enhances fentanyl and sufentanil, but not morphine, analgesia. Bansinath, M; Lovitz, M; Puig, MM; Statile, L; Turndorf, H; Warner, W, 1988)	0.52
"5 cm from the anus, 10 mg kg-1) administration of morphine hydrochloride were determined in 10 or 11-week-old male Wistar rats to compare bioavailability of morphine after the rectal dosage with that after oral administration."	( Enhanced bioavailability of morphine after rectal administration in rats. Itakura, T; Iwamoto, K; Kanba, Y; Katagiri, Y; Naora, K, 1988)	0.82
" The purpose of this study was to examine further this phenomenon in humans by characterizing the antagonist dose-response function."	( Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. Bigelow, GE; Heishman, SJ; Liebson, IA; Stitzer, ML, 1989)	0.5
") shifted the dose-response curves to morphine to the right in a parallel manner."	( Antinociceptive effects of azepexole (BHT 933) in mice. Bansinath, M; Puig, MM; Turndorf, H; Vargas, ML, 1989)	0.55
" The dose-response curves for midazolam, morphine, and their combination (each in a group of 30 patients) were determined by probit procedure and compared with isobolographic and algebraic (fractional) analyses."	( Midazolam-morphine sedative interaction in patients. Bradley, EL; Ezry, J; Fleyshman, G; Kissin, I; Tverskoy, M, 1989)	0.95
" None of the differences observed reached statistical significance, in agreement with the similarity of the dose-response curves."	( Analysis of the wheal-and-flare reactions that follow the intradermal injection of histamine and morphine in adults with recurrent, unexplained anaphylaxis and systemic mastocytosis. Bressler, RB; Kaliner, MA; Keffer, JM; Metcalfe, DD; Wright, R, 1989)	0.49
" The slope of the dose-response curve was steeper after pre-exposure."	( Behavioral effects of morphine and phencyclidine in rats: the influence of repeated testing before and after single treatment. Leys, A; Van Ree, JM, 1985)	0.58
" An inverted-U dose-response curve was obtained."	( Pharmacological evidence of a central effect of naltrexone, morphine, and beta-endorphin and a peripheral effect of met- and leu-enkephalin on retention of an inhibitory response in mice. Baratti, CM; Introini, IB; McGaugh, JL, 1985)	0.51
" We conclude that sufentanil administered in the dosage range of 19 micrograms/kg allows more rapid induction, earlier emergence from anesthesia, and faster extubation of patients than either morphine or fentanyl."	( A comparison of morphine, fentanyl, and sufentanil anesthesia for cardiac surgery: induction, emergence, and extubation. Dec-Silver, H; Harrison, WK; Sanford, TJ; Smith, NT, 1986)	0.81
" Complete dose-response data for morphine, heroin, etorphine, d- and l-ethylketazocine, d- and l-pentazocine, and d- and l-N-allylnormetazocine revealed a predominant response of hyperthermia."	( Body temperature effects of opioids in rats: intracerebroventricular administration. Adler, MW; Geller, EB; Rowan, CH, 1986)	0.55
" Using an appropriate dosage of intrathecal midazolam selective blockade of spasticity of the hind legs may be demonstrated with integrated EMG."	( [Spasticity treatment with spinal morphine or midazolam. In vitro experiments, animal studies and clinical studies on compatibility and effectiveness]. Boldt, J; Börner, U; Gerlach, H; Hempelmann, G; Hild, P; Müller, H; Oehler, KU; Zierski, J, 1986)	0.55
" However, these challenges have been conducted after relatively acute dosing with naltrexone, and tolerance to this antagonism after chronic treatment is possible."	( Nontolerance to the opioid antagonism of naltrexone. Gaspari, J; Kleber, HD; Kosten, TR; Topazian, M, 1985)	0.27
" Full dose-response curves show a 4-fold shift to the right (P less than ."	( Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms. Ling, GS; Lockhart, SH; Pasternak, GW; Spiegel, K, 1985)	0.27
" The administration of the lowest dose of EKC stimulated the release of prolactin whereas higher doses were without effect suggesting biphasic dose-response relationship."	( Identification of multiple opiate receptors through neuroendocrine responses. I. Effects of agonists. George, R; Pechnick, R; Poland, RE, 1985)	0.27
" In long-term dosing studies in rodents and primates buprenorphine did not produce the manifestations of physical dependence when treatment was stopped."	( Buprenorphine. Lewis, JW, 1985)	0.27
" The dose-response curves for the biological response were suggestive of positive cooperativity and systematically occurred at lower ligand concentrations than those for the binding of [3H] [D-Ala2, D-Leu5]enkephalin (DADLE), which were instead shallow and suggestive of a site heterogeneity or of a cooperative phenomenon."	( Multiple states of opioid receptors may modulate adenylate cyclase in intact neuroblastoma X glioma hybrid cells. Costa, T; Gramsch, C; Herz, A; Wüster, M, 1985)	0.27
" In these experiments, dose-response curves were recorded."	( New models for the evaluation of opioid effects in the guinea-pig ileum. Donnerer, J; Lembeck, F, 1985)	0.27
" Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect."	( The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol. Chesher, GB; Jackson, DM, 1985)	0.67
" Under the same treatment conditions, caffeine became a more potent antagonist of PIA-induced analgesia, and the dose-response curve for the locomotor effects of caffeine was shifted to the left."	( Changes in adenosine receptor sensitivity in morphine-tolerant and -dependent mice. Ahlijanian, MK; Takemori, AE, 1986)	0.53
" Naloxonazine also shifted full morphine dose-response curves to the right."	( Antagonism of morphine analgesia by intracerebroventricular naloxonazine. Bodnar, RJ; Pasternak, GW; Portzline, T; Simone, DA, 1986)	0.92
" The dosage of beta-FNA utilized (5 mg/kg) blocked morphine-induced analgesia (2 mg/kg morphine sulfate, SC) for each injection period (i."	( beta-Funaltrexamine (beta-FNA) and the regulation of body and brain development in rats. McLaughlin, PJ; Zagon, IS, 1986)	0.52
" pairs of time-response curves, pairs of dose-response lines were constructed at various times; these lines showed decreasing displacement with time, indicative of the disappearance of naloxone."	( Estimation of the affinity of naloxone at supraspinal and spinal opioid receptors in vivo: studies with receptor selective agonists. Heyman, JS; Koslo, RJ; Mosberg, HI; Porreca, F; Tallarida, RJ, 1986)	0.27
"5 mg/kg diazepam-morphine dose-response curve."	( The possible modulation of morphine analgesia by the supramolecular GABA receptor complex. Ayhan, IH; Palaoglu, O, 1986)	0.91
" The slope of the analgesic dose-response curve for the highly specific delta agonist, cyclic [D-Penicillamine2, D-Penicillamine5]enkephalin (DPDPE), was significantly different (flatter) from those of mu agonists or DADLE."	( Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors. Chang, KJ; Leslie, JB; Russell, RD; Su, YF; Watkins, WD, 1987)	0.27
"Systemic administration of beta-funaltrexamine (beta-FNA) 24 hr before analgesic testing produced approximately a 10-fold parallel shift in the dose-response curves of the prototypic mu agonists morphine, I-methadone, fentanyl and etorphine in the mouse abdominal constriction test."	( Use of beta-funaltrexamine to determine mu opioid receptor involvement in the analgesic activity of various opioid ligands. Hynes, MD; Leander, JD; Reel, JK; Zimmerman, DM, 1987)	0.46
" However, a U-shaped dose-response effect on morphine antinociception (3 micrograms, IT) was observed, wherein potent attenuation, moderate attenuation, or enhancement of morphine-induced antinociception was observed following the various doses tested."	( Role of spinal cord neuropeptides in pain sensitivity and analgesia: thyrotropin releasing hormone and vasopressin. Culhane, ES; Suberg, SN; Thurston, CL; Watkins, LR, 1986)	0.53
" This effect was time-dependent and dose-dependent, and the usual naloxone dose-response function could be recaptured 1 week after the pretreatment effect was obtained."	( Effects of acute morphine pretreatment on the rate-decreasing and antagonist activity of naloxone. Young, AM, 1986)	0.61
" The slope of this sigmoid dose-response curve varied with the inspirate; it increased as the concentration of CO2 was higher."	( Respiratory effects of morphine in awake unrestrained rats. Colpaert, FC; van den Hoogen, RH, 1986)	0.58
", the morphine dose-response curve was shifted to the right."	( Potentiation of disruptive effects of dextromethorphan by naloxone on fixed-interval performance in rats. Taşkin, T, 1986)	0.75
" The well-known tolerance to the hypothermic effect was confirmed by changes in the dose-response curves for latency to peak hyperthermic response."	( Tolerance to hyperthermia produced by morphine in rat. Kalant, H; Kim, C; Mucha, RF, 1987)	0.54
" Similarly, chronic dosing with acetorphan after withdrawal produced no significant effect on body weight."	( Amelioration of naloxone-precipitated opioid withdrawal symptoms by peripheral administration of the enkephalinase inhibitor acetorphan. Livingston, SJ; Rooney, KF; Sewell, RD; Smith, HJ, 1988)	0.27
" Dosing rates and rankings of pain, sedation, and liking decreased as a function of time postoperatively, but respiratory rates did not."	( Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient-controlled analgesia. Arrigo, JM; Batenhorst, RL; Baumann, TJ; Foster, TS; Graves, DA, )	0.43
" The development of tolerance following this regimen was assessed by shifts in dose-response curves to the right when animals were tested on a tail-flick device in the distinctive context."	( Tolerance to morphine in the rat: associative and nonassociative effects. Maude-Griffin, PM; Tiffany, ST, 1988)	0.64
" Systemic dosing of opiates is therefore required to reduce the cough reflex, whereas inhaled opiates may reduce the increase in Rrs after inhaled capsaicin."	( Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans. Choudry, NB; Fuller, RW; Karlsson, JA; Pride, NB, 1988)	0.27
"The respiratory-depressant effect of the benzodiazepine-derived hypnotic triazolam was investigated with a single oral dose at two and three times the usual dosage in 62 awake normal subjects."	( Ventilatory effects of single, high-dose triazolam in awake human subjects. Begle, RL; Busch, MA; Skatrud, JB, 1988)	0.27
" We administered propranolol over a wide dosage range to a different group of animals and found that a high dose (20 mg/kg) increased separation-induced coos while decreasing the activity levels."	( Effects of clonidine and propranolol on separation-induced distress in infant rhesus monkeys. Kalin, NH; Shelton, SE, 1988)	0.27
" Morphine altered dose-response curves for exogenous PGE2, evoking a parallel surmountable shift to the right, but did not affect the inotropic action of added PGF2 alpha."	( Morphine diminishes the constancy of spontaneous uterine contractions, antagonizes the positive inotropic effects of prostaglandin E2, but not of prostaglandin F2 alpha and inhibits prostaglandin E and F outputs from the uterus of ovariectomized rats. Chaud, MA; Faletti, A; Gimeno, AL; Gimeno, MA, 1988)	2.63
" A U-shaped dose-response relationship was observed for the ability of CCK-8-S to attenuate (by approximately 50%, at most) morphine-induced tail flick analgesia."	( Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics. Barbaz, BS; Hall, NR; Liebman, JM, )	0.7
" Vagotomy and atropine prevented the effect of morphine so that the dose-response relationships and the mean digoxin dose at onset of ventricular arrhythmias and the development of fatal arrhythmias were not significantly different from the control group receiving saline."	( The interrelationship of morphine and the parasympathetic nervous system in digoxin-induced arrhythmias in the guinea-pig. Rabkin, SW, 1988)	0.84
" Dose-response curves revealed that adult animals were more than 10-fold less sensitive to NMDA than their younger counterparts."	( Characterization and possible opioid modulation of N-methyl-D-aspartic acid induced increases in serum luteinizing hormone levels in the developing male rat. Bell, RD; Cicero, TJ; Meyer, ER, 1988)	0.27
" Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy."	( Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1988)	0.27
" The results of this study confirm previous reports of acute physical dependence in man and extend those findings by demonstrating a morphine dose-response function."	( Acute physical dependence in man: effects of naloxone after brief morphine exposure. Bickel, WK; Bigelow, GE; Liebson, IA; Stitzer, ML, 1988)	0.72
" This situation demonstrates the difficulties of assessing the level of sedation as well as the dosage requirements in this type of patient."	( Detection of overdosage of sedation in a patient with renal failure by the absence of lower oesophageal motility. Sinclair, ME; Suter, PM, 1988)	0.27
" Rescue use is measured over dosing intervals as test drug is titrated from a subanalgesic dose to that requiring no or minimal rescue."	( Rescue factor: a design for evaluating long-acting analgesics. Hill, CS; Homesley, H; Savarese, JJ; Thomas, GB, 1988)	0.27
"25-50 micrograms) in ICR mice, which showed a bell-shaped hyperglycemic dose-response relationship and a brief explosive motor behavior at the higher doses (25-50 micrograms)."	( Differential effects of subcutaneous and intrathecal morphine administration on blood glucose in mice: comparison with intracerebroventricular administration. Brase, DA; Dewey, WL; Lux, F, 1988)	0.52
" The need for increased dosage seems to be related not only to changes in receptor sensitivity but also to changes in pain mechanisms."	( Clinical experience of long-term treatment with epidural and intrathecal opioids--a nationwide survey. Arnér, S; Gustafsson, LL; Rawal, N, 1988)	0.27
" Yohimbine, but not naloxone, antagonized the antinociceptive effects of clonidine, whereas both yohimbine and naloxone altered the dose-response function for the effects of clonidine on blood pressure."	( Intrathecal morphine and clonidine: antinociceptive tolerance and cross-tolerance and effects on blood pressure. Gebhart, GF; Solomon, RE, 1988)	0.65
" In light of these conflicting reports, we have conducted a systematic dose-response analysis of the effects of morphine on FBM in 27 fetal lambs."	( Dual action of morphine on fetal breathing movements. Amione, J; Clare, S; Dwyer, G; Szeto, HH; Umans, JG; Zhu, YS, 1988)	0.84
" A reduced dosage of local anesthetics, as commonly recommended during pregnancy, was used."	( [Epidural anesthesia in a patient with Friedreich's ataxia]. Alon, E; Waespe, W, 1988)	0.27
" The magnitude of the activating effect depended on the dosage and time after morphine administration."	( [Mechanism of the stimulating effect of sucrose in the small intestine as affected by morphine]. Itina, LV, 1987)	0.72
" However, accumulation of morphine during multiple dosing was significant (AUC24 = 102 +/- 33 ng/mL/hr after single dose versus 212 +/- 118 ng/mL/hr after the last multiple dose)."	( Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers. Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1987)	0.57
" The diffusion of 14-18% of the epidurally injected dosage of morphine and 18-27% of dikain through the dura mater takes place depending on the segmentary level."	( [Experimental evaluation of dura mater permeability on a model of peridural analgesia with morphine and dikain]. Vitenbek, IA, 1987)	0.73
" The programmable pump allows precise dosage which is adjusted to the requirements of the individual patient."	( Continuous intraventricular morphine- or peptide-infusion for intractable cancer pain. Chrubasik, J; Mundinger, F; Weigl, K, 1987)	0.57
" Continuous administration of low dosage epidural narcotics has been shown to have less frequent side effects than bolus administration."	( Epidural catheter analgesia for the management of postoperative pain. Cullen, ML; Staren, ED, 1986)	0.27
" In contrast to the above, either morphine or [Met5]enkephalin in subthreshold dosage administrated together with the peptidase inhibitors displayed antinociceptive activity in the two groups of tests."	( Dissociated effects of inhibitors of enkephalin-metabolising peptidases or naloxone on various nociceptive responses. Aveaux, D; Ben Natan, L; Chaillet, P; Costentin, J; Schwartz, JC; Vlaiculescu, A, 1986)	0.55
" However, the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients."	( A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Cherry, DA; Cousins, MJ; Gourlay, GK, 1986)	0.5
" Dose-response curves for the different behavioral measures revealed significant effects of systemic morphine at the following dosages: The adjunctive behaviors clearly were the most susceptible to depression."	( Measurement of pain and morphine hypalgesia in monkeys. Cooper, BY; Vierck, CJ, 1986)	0.79
" When this preparation was incubated with morphine for 1 h tolerance developed to the inhibitory effect, since dose-response curves were shifted to the right."	( Yohimbine reduces morphine tolerance in guinea-pig ileum. Alamo, C; Alguacil, LF; Cuenca, E; Santos, C, 1987)	0.87
" The 4-dose twin crossover trial in which doses are adjusted sequentially is more flexible in that a wide range of doses may be studied, but it lacks the ability of the 6-dose design to provide estimates of the curvature of the dose-response slopes of the study drugs."	( Crossover trials in clinical analgesic assays: studies of buprenorphine and morphine. Houde, RW; Kaiko, RF; Rogers, AG; Wallenstein, SL, )	0.36
" After 12 generations of selective breeding, the high antinociceptive response line exhibited about 7 times steeper dose-response curve than did the low antinociceptive response line whereas only small differences were seen with saline alone."	( Selective breeding for levorphanol-induced antinociception on the hot-plate assay: commonalities in mechanism of action with morphine, pentazocine, ethylketocyclazocine, U-50488H and clonidine in mice. Belknap, JK; Danielson, PW; Laursen, SE; Noordewier, B, 1987)	0.48
" The mean dosage of bupivacaine decreased from 21."	( Comparison of continuous epidural infusion of a local anesthetic and administration of systemic narcotics in the management of pain after total knee replacement surgery. Denson, DD; Edström, HH; Hartrick, CT; Hopson, CN; Knarr, DC; Pither, CE; Raj, PP; Vigdorth, E, 1987)	0.27
" Chronic dosing with morphine or clonidine caused partial tolerance and cross-tolerance to the rise in hepatic BSP caused by an acute challenge with either agonist."	( Tolerance to effects of clonidine and morphine on sulfobromophthalein disposition in mice. Ben-Zvi, Z; Graham, CE; Hurwitz, A, 1987)	0.86
" The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement."	( Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. Evans, W; Khojasteh, A; Reynolds, RD; Savarese, JJ; Thomas, G, 1987)	0.79
" The acetylcholine dose-response curves for steroid pretreated ileum but not duodenum were significantly shifted to the right; evidence that pretreated ileum required higher dose of acetylcholine than normal to cause 50% maximal contraction."	( The effect of corticosteroid pretreatment in vivo on the contraction of guinea-pig ileum and duodenum. Alias, AK; Idid, SZ; Khalid, BA; Merican, Z; Morat, P, 1987)	0.27
" All the calcium channel blockers studied increased morphine analgesia and displaced to the left the morphine dose-response curve."	( Analgesic effects of several calcium channel blockers in mice. Baeyens, JM; Caro, G; Del Pozo, E, 1987)	0.52
" The dose-response curve for morphine (i."	( Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways. Wigdor, S; Wilcox, GL, 1987)	0.88
" The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0."	( Buprenorphine vs. morphine via the epidural route: a controlled comparative clinical study of respiratory effects and analgesic activity. Belfior, R; Berioli, MB; Bifarini, G; Dottorini, ML; Grassi, V; Paoletti, F; Pasqualucci, V; Sorbini, CA; Tantucci, C, 1987)	0.82
" Mg2+ dose-response curves also reinforced the differences in the Ca2+/CaM requirement for Gpp(NH)p- and morphine-induced inhibition."	( Ca2+/calmodulin distinguishes between guanyl-5'-yl-imidodiphosphate- and opiate-mediated inhibition of rat striatal adenylate cyclase. Ahlijanian, MK; Cooper, DM; Halford, MK, 1987)	0.49
" Patients were followed up primarily at home, supervised by a local hospice care team, and received daily dosage ranging from 60 mg to 420 mg morphine administered as 30 mg sustained-release tablets delivered at intervals from 6 to 10 hours for 'Roxanol SR' and from 8 to 14 hours for 'MS Contin'."	( The use of sustained-release morphine in a hospice setting. Sherman, LM, 1987)	0.77
" To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats."	( Irradiation exposure modulates central opioid functions. Dafny, N; Dougherty, PM, 1987)	0.47
" Morphine pharmacokinetics were also studied in cancer patients administered long-term infusions of morphine sulfate over a wide dosage range (0."	( Cerebrospinal fluid and plasma pharmacokinetics of morphine infusions in pediatric cancer patients and rhesus monkeys. Balis, FM; Greene, RF; Lester, CM; Miser, AW; Poplack, DG, 1987)	1.44
" Of the 18 patients who completed the study, all achieved satisfactory levels of analgesia on MSC, seven at q8h and 11 at q12h dosing intervals."	( Management of cancer pain with oral controlled-release morphine sulfate. Blum, RH; Kantor, TG; Kleinman, PM; Meed, SD; Savarese, JJ, 1987)	0.52
" With increasing dosage of nalbuphine there appeared to be a limit to the extent of respiratory depression."	( Respiratory function following nalbuphine and morphine in anaesthetized man. Klepper, ID; Mapleson, WW; Rosen, M; Vickers, MD, 1986)	0.53
" Dose-response and time-course experiments were carried out using both static incubation of paired hemipituitary glands and perifusion of whole glands."	( Effects of two enkephalin analogues, morphine sulphate, dopamine and naloxone on prolactin secretion from rat anterior pituitary glands in vitro. Bentley, AM; Wallis, M, 1986)	0.54
" All eight drugs produced dose-related decreases in response rates, and the buprenorphine dose-response curve was more shallow and not parallel to the others."	( Comparison of opioid self-injection and disruption of schedule-controlled performance in the baboon. Brady, JV; Griffiths, RR; Lukas, SE, 1986)	0.27
"A study of the liver N-demethylase activity in rats treated with different dosage schedule of morphine, or with a single dose of haloperidol was carried out."	( N-demethylase activity in the rat liver following morphine and haloperidol treatment. Daniel, W; Melzacka, M, )	0.6
" Tolerance to the acute effects of morphine on phenol red disposition is probably due to lessened response of blood flow or tubular function in chronically dosed mice."	( Tolerance to morphine effects on renal disposition of xenobiotics in mice. Garty, M; Hurwitz, A, 1986)	0.92
" The immunoreactivity of the tissue extracts gave dose-response lines in the radioimmunoassay for met-enkephalin which were near parallel to that for the standard."	( Evidence for intrinsic regulation of met-enkephalin-immunoreactivity in gastroenteropancreatic tissues of the rat. Degler, T; Feurle, GE; Frank, B, 1986)	0.27
" Morphine analgesic effect during subchronic dosage (50 mg/kg a day) was gradually decreased."	( Stimulation-produced analgesia under repeated morphine treatment in rats. Morozova, AS; Zvartau, EE, 1986)	1.44
" Dose-response curves for the convulsive effect of pentylenetetrazol obtained at the peak of the withdrawal signs shifted greatly to the left in alcohol withdrawn animals but less in barbital withdrawn animals."	( Differentiation of alcohol and barbital physical dependence. Kaneda, H; Kaneto, H; Kawatani, S, 1986)	0.27
" Patients given continuous infusions required more narcotic to control their pain and had more side effects than those treated with bolus injections alone, suggesting a dose-response relationship between narcotic dose and several known side effects."	( Intravenous narcotic therapy for children with severe sickle cell pain crisis. Buchanan, GR; Cole, TB; Smith, SJ; Sprinkle, RH, 1986)	0.27
"Experimentation with the "in vitro" methodology allowed the authors to study the effects of several pharmacological substances on human and animal tissue, making possible a qualitative assessment of activity, the quantitative dose-response relationships, the possible existence of specific drug receptors and the action, competitive or non-competitive, of a given antagonist."	( In vitro study on isolated tissues: applications to perinatology. Branconi, F; D'Alessandro, A; Di Tommaso, M; Farruggia, A, 1986)	0.27
" Comparisons of dose-response curves and efficacies demonstrated that d-NANM was more similar to PCP in its effectiveness in depressing the flexor and skin twitch reflexes than was l-NANM."	( Pharmacologic and reinforcing properties of phencyclidine and the enantiomers of N-allylnormetazocine in the dog. Risner, ME; Shannon, HE; Vaupel, DB, 1986)	0.27
" The mean daily morphine dosage was 103 +/- 36 mg and the maximum daily dosage was 170 +/- 65 mg."	( Morphine in tetanus--the management of sympathetic nervous system overactivity. Calver, AD; Hariparsad, D; Pather, M; Rocke, DA; Wesley, AG, 1986)	2.06
"8 ng/ml depending on daily dosage and body weight."	( [The pharmacokinetics of continuous peridural morphine infusion]. Gips, H; Hempelmann, G; Krumholz, W; Lüben, V; Müller, H; Zierski, J, 1986)	0.53
" When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken."	( Reassessment of verbal and visual analog ratings in analgesic studies. Littman, GS; Schneider, BE; Walker, BR, 1985)	0.27
" Most importantly, however, we showed that the GPT-LHRH produced equivalent, parallel shifts to the right in the dose-response curves for LHRH and naloxone, indicative of competitive inhibition."	( Luteinizing hormone releasing hormone mediates naloxone's effects on serum luteinizing hormone levels in normal and morphine-sensitized male rats. Cicero, TJ; Meyer, ER; Miller, BT; Schmoeker, PF, 1985)	0.48
" A valid dose-response curve was obtained for both drugs with no significant deviation from parallelism."	( Comparative evaluation of ciramadol (WY-15.705), morphine and placebo for treatment of postoperative pain. Camu, F; Van den Abeele, G, 1985)	0.52
" Continuous subcutaneous infusion of morphine is a practical and effective means of achieving post-operative analgesia but, as with other mandatory dosing regimens, relative overdosage may occur."	( Continuous subcutaneous infusion of morphine for postoperative pain relief. Allan, MW; Burrow, LM; Goudie, TA; Grant, IS; Lonsdale, M; Macrae, WA, 1985)	0.82
" Schedule-controlled responding was disrupted when morphine maintenance was abruptly discontinued but not when the maintenance dosage was gradually reduced to zero."	( Behavioral effects of naloxone and nalorphine preceding and following morphine maintenance in the rhesus monkey. Bergman, J; Schuster, CR, 1985)	0.75
"A randomized double-blind study compared the dose-response relationship of epidural morphine for postoperative pain relief in two groups of patients whose surgical procedures would result in either moderate (femoral-popliteal bypass) or severe (total knee replacement) postoperative pain."	( Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients: a dose-response study. Allen, PD; Concepcion, M; Covino, BG; Cullen, D; Patterson, MK; Sheskey, M; Walman, T, 1986)	0.91
" These results provide evidence that tolerance for cocaine used as a discriminative stimulus occurs as a function of chronic dose, dosing regimen and class of drug administered."	( Characteristics of tolerance, recovery from tolerance and cross-tolerance for cocaine used as a discriminative stimulus. Emmett-Oglesby, MW; Wood, DM, 1986)	0.27
" This dosing method produced high plasma naltrexone levels (350 ng/ml) by 1 hr which declined over an implant period of 192 hr (24 ng/ml)."	( Pharmacokinetics and pharmacodynamics of subcutaneous naltrexone pellets in the rat. Cohen, AH; Inturrisi, CE; Yoburn, BC, 1986)	0.27
" The degree of drug tolerance was assessed by determining cumulative dose-response functions for morphine before, during and after chronic administration."	( Modification of morphine tolerance by behavioral variables. Sannerud, CA; Young, AM, 1986)	0.83
" After these dose-response curve determinations, chronic daily treatment with haloperidol (0."	( Effects of drugs on schedule-controlled behavior in rats during chronic haloperidol administration. McMillan, DE; Rastogi, SK, 1985)	0.27
" The N-methyl-quaternary analog of naloxone (methylnaloxone, which presumably entails selective action at opiate receptors outside the CNS) was also effective, indicating peripheral effects at the dosage level used (0."	( Colonic motor responses in the pony: relevance of colonic stimulation by opiate antagonists. Bardon, T; Roger, T; Ruckebusch, Y, 1985)	0.27
"Low dosage epidural morphine (4 mg) provided adequate postoperative pain relief in patients undergoing elective cesarean section under epidural analgesia."	( Epidural morphine as postoperative analgesic following cesarean section under epidural analgesia. Aaltonen, L; Aärimaa, L; Erkkola, R; Kanto, J, 1985)	1.01
"Male and female normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) all responded to morphine treatment with biphasic dose-response curves, exhibiting hyperthermia at low doses and hypothermia at higher doses."	( Sex and strain differences in morphine-induced temperature effects in WKYs and SHRs. Barlament, J; Quock, RM; Vaughn, LK; Wojcechowskyj, JA, 1985)	0.77
" These data indicate that an interindividual variation in morphine pharmacokinetics is one factor responsible for varying dosage requirements in children with cancer."	( Variation in morphine pharmacokinetics in children with cancer. Miser, AW; Miser, JS; Nahata, MC; Reuning, RH, 1985)	0.88
" at a dosage 1000 times lower than that of morphine on a molar basis."	( Comparative study on the electrophysiological responses at thalamic level to different analgesic peptides. Biella, G; Braga, PC; Fraschini, F; Guidobono, F; Pecile, A; Tiengo, M, 1985)	0.53
" At 30 min, the dose-response curve was shifted to the right."	( Chronic stress, aging and morphine analgesia: chronic stress affects the reactivity to morphine in young mature but not old rats. Girardot, MN; Holloway, FA, 1985)	0.57
" Naloxone, in the dosage used (40 micrograms/kg body wt as a bolus, followed by 10 micrograms/kg body wt X h) had no independent effects on motility or flow, but did blunt the stimulatory effects of morphine and atropine on migrating motor complexes."	( Effects of morphine and atropine on motility and transit in the human ileum. Borody, TJ; Haddad, A; Phillips, SF; Quigley, EM; Tucker, RL; Wienbeck, M; Zinsmeister, AR, 1985)	0.85
" In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1)."	( Morphine--caffeine analgesic interaction in rats. Bradley, EL; Brown, PT; Kissin, I; Person, DL; Vinik, HR; Xavier, AV, 1985)	1.96
" On combined use of gidifen and analgesics applied in a definite dosage range the analgesic effect is potentiated."	( [Pain-alleviating action of gidifen and its combinations with analgesics]. Aleksandrova, GM; Efremova, GN; El'tsova, ZI; Milogradova, GP; Zorian, EV, )	0.13
" Under conditions of high stress, rats first showed diminished, and then enhanced, hyperthermic responding across repeated morphine dosing (5 or 35 mg/kg)."	( Influence of stress on morphine-induced hyperthermia: relevance to drug conditioning and tolerance development. Baker, TB; Tiffany, ST; Zelman, DC, 1985)	0.79
" It was concluded that a rectal solution adjusted to pH 7 to 8 provided an entirely adequate dosage form."	( Drastic improvement in the rectal absorption profile of morphine in man. Meijer, DK; Moolenaar, F; Visser, J; Yska, JP, 1985)	0.52
" The pharmacodynamic consequences of these dosage characteristics are the rapid development of tolerance and maintenance of physical dependence during the period of the implant."	( Pharmacokinetics and pharmacodynamics of subcutaneous morphine pellets in the rat. Chen, J; Huang, T; Inturrisi, CE; Yoburn, BC, 1985)	0.52
" The absence of any effects of a 2-mg/kg dose of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the severe side effects produced by 10 mg/kg prevented determination of its dose-response relationship."	( Shock titration in the rhesus monkey: effects of opiate and nonopiate analgesics. Bloss, JL; Hammond, DL, 1985)	0.27
" After the lower dosage of morphine the plasma concentrations never exceeded 10 ng X ml-1, whereas the mean peak plasma concentration was 25."	( Rectally administered morphine: plasma concentrations in children premedicated with morphine in hydrogel and in solution. Westerling, D, 1985)	0.88
" Due to the rather high dosage necessary (1-2 mg/ml), well-known side-effects of these opiates must also be taken into consideration."	( [Local anesthetic effects of morphine and naloxone]. Gilly, H; Kramer, R; Zahorovsky, I, 1985)	0.56
" The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established."	( Monoamine mediation of the morphine-induced activation of mice. Carroll, BJ; Sharp, PT, 1972)	0.77
" Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs."	( An implanted reservoir of morphine solution for rapid induction of physical dependence in rats. Goode, PG, 1971)	0.83
" Tolerance was manifested by a shift to the right in the dose-response curve for morphine after mice were treated repeatedly with morphine."	( Tolerance to morphine-induced increases in [14C]catecholamine synthesis in mouse brain. Bednarczyk, JH; Sheldon, MI; Smith, CB; Villarreal, JE, 1970)	0.84
" Log dose-response curves to oxotremorine and acetylcholine were similar and both drugs were competitively antagonized by atropine."	( Investigation of the mechanism of action of oxotremorine on the guinea-pig isolated ileum preparation. Cox, B; Hecker, SE, 1971)	0.25
" These results show that tumorigenic events are dictated by the duration of opiate receptor blockade rather than the dosage of opiate antagonist, and provide compelling evidence that endogenous opioid systems play a crucial role in neuro-oncogenic expression."	( Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer. McLaughlin, PJ; Zagon, IS, 1984)	0.27
" Dose-response experiments indicated that cyclo (leu-Gly) was much more potent than MIF in these tests."	( Development of narcotic tolerance and physical dependence: effects of Pro-Leu-Gly-NH2 and cyclo (Leu-Gly). Bhargava, HN; Ritzmann, RF; Walter, R, 1980)	0.26
" While the dose-response curves for the antipsychotic drugs were parallel, had steep slopes and similar maxima, the curves for morphine and oxotremorine were irregularly shaped but the curve for morphine in the TO had some similarity to that of the antipsychotic drugs."	( The differential effects of morphine, oxotremorine and antipsychotic drugs on DOPAC concentrations in rat brain. Stanley, M; Wilk, S, 1980)	0.76
"5 mum produced a 1000 fold shift in the opiate dose-response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone."	( Opiate-like analgesic activity in general anaesthetics. Lawrence, D; Livingston, A, 1981)	0.26
") produced a dose-response curve with a reduced maximum effect."	( Relative involvement of receptor subtypes in opioid-induced inhibition of intestinal motility in mice. Takemori, AE; Ward, SJ, )	0.13
" Similar dose-response curves in an apparent sine-wave pattern were noted with both MIF-1 and naloxone when comparisons were made both at 20 minutes after administration of morphine and over the entire 150 minutes of the experiment."	( Similar antagonism of morphine analgesia by MIF-1 and naloxone in Carassius auratus. Ehrensing, RH; Kastin, AJ; Michell, GF, 1982)	0.77
" A reliable dose-response and time-response relations were observed for both groups of analgesics."	( A new method for the rapid measurement of analgesic activity in rabbits. Ayhan, IH; Melli, M; Türker, RK, 1983)	0.27
" [14C]Morphinone-cysteine conjugate was detected in proteolytic digests of mouse liver protein dosed with radiolabeled morphine."	( Studies on the mechanism of covalent binding of morphine metabolites to proteins in mouse. Ishida, T; Kido, Y; Nagamatsu, K; Terao, T; Toki, S, )	0.6
" In contrast, removal of the morphine pellet 3 hours prior to the analgesic evaluation apparently unmasked the expression of tolerance and cross-tolerance as evidenced by a three fold, parallel shift to the right of the analgesic dose-response curve for subcutaneously administered etorphine and methadone and a seven fold shift to intracerebroventricularly administered morphine."	( Differential analgesic cross-tolerance to morphine between lipophilic and hydrophilic narcotic agonists. Paktor, J; Vaught, JL, 1984)	0.82
" We have also found that the route of administration, dosage schedule, and satiation of animals may affect the distribution and metabolism of drugs, and this in turn may change their pharmacological effects."	( Pharmacokinetic aspects of some behavioral effects of psychotropic drugs. Melzacka, M, )	0.13
" One group of experiments established a dose-response range."	( Effects of morphine on glucose homeostasis in the conscious dog. Abumrad, NN; Cherrington, AD; Lacy, DB; Lacy, WW; McRae, JR; Radosevich, PM; Steiner, KE; Williams, PE, 1984)	0.66
" More than 45% of ventromedial hypothalamic units reacted in a dose-response fashion to local application of morphine."	( Microiontophoretic application of morphine and naloxone to neurons in hypothalamus of rat. Dafny, N; Prieto-Gomez, B; Reyes-Vazquez, C, 1984)	0.76
"01 mg/kg IP, the dose-response pattern for MIF-1 resembling an inverted-U."	( Tyr-MIF-1 and MIF-1 are active in the water wheel test for antidepressant drugs. Abel, DA; Coy, DH; Ehrensing, RH; Graf, MV; Kastin, AJ, 1984)	0.27
"-butyl-amino-ethanol hydrochloride (mabuterol) was tested in male rats dosed with 20, 100 and weekly increasing doses of 20, 40, 60, 80 and 100 mg/kg over 7 weeks."	( Special toxicology--physical dependence potential, antigenicity and mutagenicity--of mabuterol. Amemiya, K; Arika, T; Asano, T; Kudoh, M; Nakamura, M, 1984)	0.27
" Dose-response curves were constructed using the rat tail pressure test for analgesia which indicated a rank order of potency of buprenorphine much greater than morphine greater than butorphanol greater than xorphanol = nalbuphine."	( Physical dependence induced by opiate partial agonists in the rat. Howlett, GJ; McCarthy, PS, 1984)	0.46
" Adverse reactions occurred more often with higher doses of morphine and codeine; the dose-response relationship could not be evaluated for the other three drugs."	( Clinical effects of parenteral narcotics in hospitalized medical patients. Miller, RR, 1980)	0.5
" IF produced a long-lasting increase in firing discharges and exhibited dose-response characteristics."	( Novel effects of interferon on the brain: microiontophoretic application and single cell recording in the rat. Dafny, N; Prieto-Gomez, B; Reyes-Vazquez, C, 1982)	0.26
" Morphine in the dosage used did not influence the intradental sensory nerve conductivity."	( Morphine inhibits substance P release from peripheral sensory nerve endings. Brodin, E; Gazelius, B; Olgart, L; Panopoulos, P, 1983)	2.62
" Specifically in the case of morphine it is clear that: it is a very effective analgesic given orally, dosage must be individualized, parenteral use or exotic analgesic 'cocktails' are usually unnecessary, and tolerance, dependence and respiratory depression are rarely common or serious problems which prevent effective pain control provided morphine is used appropriately in accordance with its pharmacological characteristics."	( Oral morphine in chronic cancer pain. Walsh, TD, 1984)	1.07
" Although the patient gave no previous history of narcotic use or abuse, he required morphine dosing rates as high as 56 mg/h to maintain adequate analgesia."	( Extraordinary analgesic requirement in a patient previously unexposed to narcotics. Batenhorst, RL; Baumann, TJ; Bennett, RL; Foster, TS; Graves, DA; Griffen, WO; Plumlee, JE, )	0.36
"3 mg/kg) produced a 3-fold shift to the right of the cyclazocine dose-response curve but did not completely block the cyclazocine-like stimulus effects of either SKF 10,047 or ethylketocyclazocine."	( Discriminative stimulus effects of prototype opiate receptor agonists in monkeys. Holtzman, SG; Teal, JJ, 1980)	0.26
" Morphine's direct effect on activity is believed to have a biphasic dose-response curve; therefore, the relation of dose to conditioning was also studied."	( Conditioned increases in locomotor activity produced with morphine as an unconditioned stimulus, and the relation of conditioning to acute morphine effect and tolerance. Kalant, H; Mucha, RF; Volkovskis, C, 1981)	1.42
" The parallelism of the dose-response curves of opiates in the presence and absence of naloxone indicated competitive reversible antagonism."	( Opiate receptors in the rabbit iris. Dal Bello, A; Drago, F; Gorgone, G; Moro, F; Panissidi, G; Scapagnini, U; Spina, F, 1980)	0.26
" A dose-response investigation of morphine's action (5, 10, 15 and 20 mg/kg) in additional animals receiving 10 daily administrations of ECS reveals that a greater tolerance to morphine's motor inhibitory effect than to its analgesic effect results from repeated ECS administration."	( Different opioid systems may participate in post-electro-convulsive shock (ECS) analgesia and catalepsy. Frenk, H; Urca, G; Yitzhaky, J, 1981)	0.54
" 2 Buprenorphine revealed a bell-shaped dose-response curve for antinociception peaking at approx."	( In vivo receptor binding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. Dum, JE; Herz, A, 1981)	0.26
" Dose-response curves for serotonin before morphine application and in the presence of morphine show a noncompetitive mechanism of morphine-serotonin interaction."	( [Naloxone-dependent morphine-induced depression of the snail response to serotonin]. Bezrukova, LV; Solntseva, EI, 1981)	0.85
" Analyses of all measures revealed a significant effect of morphine dose, although the shape of the dose-response curve differed for individual responses."	( Altered behavioral responsivity to morphine during the periadolescent period in rats. Horowitz, GP; Lipovsky, J; Spear, LP, 1982)	0.78
" Thus, both sites demonstrated similar dose-response relationships, both responding to at least 100 times lower doses of enkephalins than MS."	( Characterization of opiate-mediated responses of the feline ileum and ileocecal sphincter. Clain, CJ; Cohen, S; Ouyang, A; Snape, WJ, 1982)	0.26
" In the presence of 30 microM morphine, the dose-response curve of beta-endorphin shifted to the right by about 10-fold."	( Partial agonistic action of morphine in the rat vas deferens. Ishii, K; Kato, R; Muraki, T; Yamamoto, S, 1981)	0.85
"The dose-response curve for morphine-induced stimulation of striatal dopamine metabolism was shifted to the right in mice which had been withdrawn for 24 hours after chronic consumption of an ethanol-containing liquid diet."	( Alterations in opiate receptor function after chronic ethanol exposure. Hoffman, PL; Tabakoff, B; Urwyler, S, 1982)	0.56
") and 60 min before testing, it produced the theoretically predicted alterations in the morphine dose-response relation that are indicative of partial receptor blockade."	( The affinity of morphine for its pharmacologic receptor in vivo. Cowan, A; Tallarida, RJ, 1982)	0.83
" Parallel dose-response lines were obtained for the two opioid agonists but the effect of EKC was more resistant to naloxone antagonism."	( Mu and kappa opioid agonists elevate brain stimulation threshold for escape by inhibiting aversion. Bonnet, KA; Carr, KD; Simon, EJ, 1982)	0.26
" In a further series of tests, a 50 mg/kg dose of naloxazone 20 hr prior to the assessment of morphine or metkephamid analgesia in the mouse hot plate test substantially shifted the dose-response curve for morphine to the right, while leaving the dose-response curve for metkephamid unchanged."	( Cross-tolerance studies distinguish morphine- and metkephamid-induced analgesia. Frederickson, RC; Hynes, MD, )	0.63
" Under the same conditions of dosage and time course of administration the activities of relevant mucosal enzymes were studied."	( Effects of morphine on net water absorption, mucosal adenylate cyclase activity and PGE2 metabolism in rat intestine. Smith, G; Tonge, A; Turnberg, L; Warhurst, G, 1982)	0.65
"The relationship between opiate binding density and morphine-induced catalepsy was estimated via dose-response analysis of the brain sites in which naloxone microinjections reversed the catalepsy induced by intraperitoneal morphine."	( Reversal of morphine-induced catalepsy by naloxone microinjections into brain regions with high opiate receptor binding: a preliminary report. Bozarth, M; Levitt, RA; Wilcox, RE, 1983)	0.9
" It increased the IC50 values and slopes of their dose-response curve for enkephalins and their analogs, and shifted to the right the curves for FK33824, levorphanol and normorphine."	( Functional opiate receptor in mouse vas deferens: evidence for a complex interaction. Garzón, J; Lee, NM; Sánchez-Blázquez, P, 1983)	0.46
" 5-HTP alone (200 mg/kg) increased wet dog shakes epissodes, whereas TP alone in the same dosage practically did not have any influence on the wet dog shakes in morphine-dependent rats."	( The role of central serotoninergic neurotransmission in the morphine abstinence syndrome in rats. Kruszewska, A; Langwiński, R, 1983)	0.7
"Agonist/antagonist (Ag/Ant) analgesics possess bell-shaped dose-response curves with regard to nigrostriatal dopamine (DA) metabolism in the rat."	( Agonist/antagonist analgesics and nigrostriatal dopamine metabolism in the rat: evidence for receptor dualism. McQuade, P; Richard, JW; Thakur, M; Wood, PL, 1983)	0.27
" The application of naloxone alone in naive and morphine-dependent rats demonstrated that the PF units responded in a characteristic dose-response manner to incremental naloxone administration."	( Microiontophoretically applied morphine and naloxone on single cell activity in the parafasciculus nucleus of naive and morphine-dependent rats. Dafny, N; Reyes-Vazquez, C, 1984)	0.81
" An increase in the naloxone dosage (up to 1 mg/kg) was necessary to demonstrate the naloxone antagonistic effect (8-fold increase in the morphine ED50 value) when morphine was given with halothane."	( Effect of morphine on the heart rate response to noxious stimulation: interaction with halothane and naloxone. Kerr, RC; Kissin, I; Smith, RL, 1984)	0.87
" Respiratory frequency was dose-dependently depressed by FK-33824 and DADLE ; dose-response curves with morphine and D-Ser2- Thr6 could not be obtained for technical reasons."	( A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists. Flórez, J; Pazos, A, 1984)	0.48
", delayed nociceptive reaction on a 55 degrees C hot-plate with a dose-response curve not readily fitting a single straight line; this effect was antagonized by high doses of naloxone."	( Bremazocine induces antinociception, but prevents opioid-induced constipation and catatonia in rats and precipitates withdrawal in morphine-dependent rats. Gambino, MC; Petrillo, P; Tavani, A, 1984)	0.47
"0 mg/kg) produced dose-related shifts to the right in the dose-response curves for the discriminative stimulus and rate-decreasing effects of morphine and ethylketazocine without affecting the response produced by meperidine."	( Narcotic discrimination in pigeons: antagonism by naltrexone. Herling, S; Solomon, RE; Valentino, RJ; Woods, JH, 1984)	0.47
" Dose-response curves for subcutaneous (SC) morphine (0."	( Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Iversen, SD; Mucha, RF, 1984)	0.83
" Footshock intensity thresholds for eliciting locomotion were determined and dose-response curves for EKC and MS analgesia were obtained."	( Analgesic effects of ethylketocyclazocine and morphine in rat and toad. Aleman, DO; Carr, KD; Holland, MJ; Simon, EJ, 1984)	0.53
" Higher dosage of narcotic administered during anesthetic induction did not temper increase in metabolic rate observed after unclamping."	( Abdominal aortic cross-clamping. Metabolic and hemodynamic consequences. Askanazi, J; Damask, MC; Hyman, AI; Rodriguez, J; Rosenbaum, SH; Weissman, C, 1984)	0.27
" Simultaneous application of Hi and 10 micrograms of diphenhydramine, pyrilamine or promethazine, apparently causing no analgesic effect from a single administration, caused a parallel shift of the dose-response curve of Hi to the right."	( Analgesic effect of histamine induced by intracerebral injection into mice. Chung, YH; Kamei, C; Miyake, H; Tasaka, K, 1984)	0.27
" There were no significant differences between dosage forms in mean morphine-3-glucuronide concentrations at individual time points or over the entire period."	( Plasma concentrations following single doses of morphine sulfate in oral solution and rectal suppository. Ellison, NM; Lewis, GO, )	0.62
" In most experimental situations, indications for bell-shaped dose-response curves of DSIP were found."	( Some pharmacological effects of delta-sleep-inducing peptide (DSIP). Aeppli, L; Haefely, W; Polc, P; Scherschlicht, R, 1984)	0.27
"From birth to day 21, rat offspring received daily injections of naltrexone at a dosage that blocked morphine-induced analgesia 24 hours a day."	( Increased brain size and cellular content in infant rats treated with an opiate antagonist. McLaughlin, PJ; Zagon, IS, 1983)	0.48
" Besides the advantage of stronger and longer duration, small dosage and minor central depressive side effects, epidural opiate analgesia has proven to result in positive clinical consequences."	( [Peridural opiate analgesia. Clinical results of a 2-year study]. Brämswig, H; Piepenbrock, S; Tryba, M; Zenz, M, 1983)	0.27
" The defensive biting response to heat shows reliable dose-response effects with morphine which compare well with our similar upper body device (Rosenfeld et al."	( A new, reliable lower-body nociception device for unrestrained animals yields data comparable to a new portable version of the face-rub test. Gribben, D; Rosenfeld, JP, 1983)	0.49
" This has brought about a reconsideration upon the usefulness of neonatal screenings and this goes for the most recent method based on the dosage of blood trypsin levels."	( [Diagnosis of cystic fibrosis]. Battistini, A, )	0.13
" The data indicate that morphine pharmacokinetics change after chronic treatment and depend on dosage schedule and that plasma concentration of morphine may not reflect the drug level in tissues, particularly in the central nervous system."	( Changes in morphine pharmacokinetics in nervous and peripheral tissues following different schedules of administration. Adamus, A; Danek, L; Melzacka, M; Vetulani, J, 1983)	0.96
" We define dosing rules for a loading dose followed by a continuous intravenous infusion of morphine sulfate to achieve a serum morphine concentration of 75 micrograms/L."	( Pharmacokinetics of intravenous morphine in balanced anesthesia: studies in children. Chinyanga, H; Endrenyi, L; Mac Leod, S; Soldin, S; Vandenberghe, H, 1983)	0.77
" Although morphine (ID50 = 4 micrograms) was a very potent analgesic when given intracerebroventricularly, very shallow dose-response curves were obtained with the other substances which promoted less than 30% of inhibition at doses up to 250 micrograms."	( The peripheral analgesic effect of morphine, codeine, pentazocine and d-propoxyphene. Ferreira, SH; Lorenzetti, BB; Molina, N; Vettore, O, 1983)	0.95
" Naloxone dose-response curves revealed that the naloxone ED50 was reduced by either morphine pretreatment regimen, but was much more pronounced in pellet-implanted animals [181."	( Morphine-induced supersensitivity to the effects of naloxone on luteinizing hormone secretion in the male rat. Cicero, TJ; Meyer, ER; Owens, DP; Schmoeker, PF, 1983)	1.93
" Dosing rates were studied with regard to the time of day."	( Morphine requirements using patient-controlled analgesia: influence of diurnal variation and morbid obesity. Batenhorst, RL; Bennett, RL; Foster, TS; Graves, DA; Griffen, WO; Wettstein, JG; Wright, BD, )	1.57
" d-Amphetamine, cocaine, and caffeine each had the effect of elevating both bite and lever press responses; nicotine, chlorpromazine, chlordiazepoxide, and diazepam each elevated lever press responding while depressing bite responding across a portion of the dosage range; phenobarbital, alcohol, and morphine had the effect of depressing both bite and lever press responses but lever pressing was selectively more depressed than biting."	( Unique influences of ten drugs upon post-shock biting attack and pre-shock manual responding. Emley, GS; Hutchinson, RR, 1983)	0.44
" One subject who was administered dextroamphetamine did not produce a wave consistent with amphetamine with a dosage of 5 mg."	( Qualitative measurement of drugs. Gilbert, LM; Golz, A; Komorowski, FS; Westerman, ST, 1984)	0.27
" To investigate the extent to which this may be due to different experimental parameters, foot-shock intensity and dosage of morphine were systematically varied in a passive-avoidance task."	( Facilitation or inhibition of memory by morphine: a question of experimental parameters. Classen, W; Mondadori, C, 1984)	0.74
" The dose-response curve was an inverted U in this range of dose."	( Possible interaction between central cholinergic muscarinic and opioid peptidergic systems during memory consolidation in mice. Baratti, CM; Huygens, P; Introini, IB, 1984)	0.27
" The factors affecting the release of drug from the delivery system were the ratio of cholesterol to naltrexone, drug loading level and surface area to unit volume of dosage form."	( An improved long-acting delivery system for narcotic antagonists. Misra, AL; Pontani, RB, 1981)	0.26
" In the remaining 13 patients nitroglycerin produced partial relief of pain in 17 +/- 5 minutes and complete relief in 127 +/- 65 minutes, requiring a cumulative dosage of 23."	( Large dose sublingual nitroglycerin in acute myocardial infarction: relief of chest pain and reduction of Q wave evolution. Kim, YI; Williams, JF, 1982)	0.26
" The increasing morphine dosage was associated with progressive rightward displacements and ultimately decreases in the slope of the CO2 response curves."	( Analgesic and respiratory depressant activity of nalbuphine: a comparison with morphine. DiFazio, CA; Gal, TJ; Moscicki, J, 1982)	0.84
" Hypophysectomy altered the slope of the dose-response curve for morphine antinociception without significantly changing the ED50."	( Endocrine influences on the actions of morphine. II. Responses to pituitary hormones. Carlson, HE; George, R; Kasson, BG, 1983)	0.77
"0 mg/kg) shifted the clonidine dose-response curves to the right, suggesting competitive antagonism."	( An analysis of the effects of systemically administered clonidine on the food and water intake of rats. Sanger, DJ, 1983)	0.27
" In 86 units, morphine at any dosage failed to alter neuronal activity, but in 54 of these units naloxone nevertheless induced alterations in firing rates."	( Dose effects of morphine on the spontaneous unit activity recorded from the thalamus, hypothalamus, septum, hippocampus, reticular formation, central gray, and caudate nucleus. Bergmann, F; Burks, TF; Dafny, N, 1983)	0.97
" Nevertheless, the antinociceptive action of vasopressin does not appear to be secondary to its pressor activity, since phenylephrine failed to induce an antinociceptive effect at a dosage that mimicked the pressor response to vasopressin."	( Vasopressin-induced antinociception: an investigation into its physiological and hormonal basis. Berntson, GG; Berson, BS; Kirk, WT; Torello, MW; Zipf, W, 1983)	0.27
" The depressive effect was significantly dose-related (with linear semi-logarithmic dose-response curve) and naloxone-reversible."	( Low dose of morphine strongly depresses responses of specific nociceptive neurones in the ventrobasal complex of the rat. Benoist, JM; Gautron, M; Guilbaud, G; Kayser, V, 1983)	0.64
" In a similar dose-response relationship, injections of morphine into this area inhibited the reflex activation of alpha-motoneurones by mild tetanic stimulation of the ipsilateral peroneal nerve (flexor alpha-motoneurones) in halothane-anesthetized rats."	( Is morphine-induced akinesia related to inhibition of reflex activation of flexor alpha-motoneurones? Role of the nucleus accumbens. Havemann, U; Kuschinsky, K; Winkler, M, 1982)	1.13
" All along gestation, the dosage was gradually increased up to the final dose of 56 mg/kg/day on the 16th day when the treatment was interrupted."	( Morphine treatment during rat pregnancy: neonatal and preweaning consequences. Lapointe, G; Nosal, G, 1982)	1.71
" Group II drugs, upon reaching a threshold value, cause first a dose-dependent increase in water intake to a maximum; additional dosage increments produce a dose-dependent decrease."	( A simple animal test system to predict the likelihood of a drug causing human physical dependence. Maickel, RP; Zabik, JE, 1980)	0.26
" In a second experiment, rats were injected for ten days with the same dosage of naloxone."	( Behavioral alterations produced by chronic naloxone injections. Baker, MJ; Hood, JL; Layng, MP; Malin, DH; Swank, P, 1982)	0.26
" In 15 patients after upperabdominal surgery the overall mean dosage of morphine was 8,85 mg within three days."	( [Epidural morphine injections for the treatment of pain]. Otten, B; Otten, G; Piepenbrock, S; Zenz, M, 1980)	0.9
" It is suggested that previously reported respiratory depression using these techniques is associated with the administration of other analgesics contemporaneously; that dosage should be limited to one-fifth of the estimation intramuscular dose; and that patients should be observed in a recovery ward for 24 hours."	( Postoperative analgesia in major orthopaedic surgery. Epidural and intrathecal opiates. Barron, DW; Strong, JE, 1981)	0.26
"Experiments on rabbits showed the summation of analgesia induced by electric stimulation of biologically active points (BAP) and by administration of morphine and fentanil within a certain dosage range."	( [Action of morphine and fentanyl during the electrostimulation of biologically active points]. Iasnetsov, VV; Komendantova, MV; Zorian, EV, )	0.72
"Insulin and glucagon release from monolayer pancreatic islet cell cultures were inhibited in a dose-response fashion by various enkephalins."	( Disparate effects of enkephalin and morphine upon insulin and glucagon secretion by islet cell cultures. Ensinck, JW; Fujimoto, WY; Kanter, RA, 1980)	0.54
" A significant shift of the normal dose-response curve towards the right was seen after electroshock."	( Reduction in opiate activation after chronic electroconvulsive shock--possible role for endorphins in the behavioral effects of convulsive shock treatment. Katz, RJ; Schmaltz, K, 1980)	0.26
" An additional study was conducted in which six subjects took 0 (placebo), 1, 2, and 4 gm/day of AA to determine the dose-response effect of AA on histamine skin tests."	( The effect of ascorbic acid on cutaneous and nasal response to histamine and allergen. Danziger, RE; Fortner, BR; Nelson, HS; Rabinowitz, PS, 1982)	0.26
" Other experiments involving intracisternal dosing with this long acting form at higher levels (0."	( Effects of enkephalins versus opiates on locomotor activity of the horse. Burns, P; Combie, JD; Nugent, TE; Tobin, T; Weld, JM, 1982)	0.26
" Buprenorphine showed a bell-shaped dose-response curve in the mouse D'Amour-Smith's test at high stimulus intensity."	( [Analgesic and narcotic antagonist effects of buprenorphine (author's transl)]. Hiyama, T; Shintani, S; Tsutsui, M; Yasuda, Y, 1982)	0.26
" These data would suggest that, at least in respect to the effects of narcotics on water intake, naloxone is a partial agonist of the nalorphine type, but the slopes of naloxone and of morphine dose-response regression lines are not in keeping with this hypothesis."	( Dual effect of naloxone on drinking behaviour of rats. Cantalamessa, F; de Caro, G; Massi, M; Micossi, LG, 1982)	0.46
" The dose-response curves for both were shifted to the right in non-parallel fashion with decreased slopes and antidiuretic efficacies."	( Cross tolerance to etorphine in rats tolerant to morphine-induced antidiuresis. Fuhrman-Lane, C; Fujimoto, JM; Tseng, LF, 1982)	0.52
"Adult proestrous rats were subjected to either electrochemical or electrical stimulation of the medial preoptic area after ovulation-blocking dosage with either pentobarbital (PTBL), morphine, chlorpromazine, or atropine."	( Similarity of luteinizing hormone surges induced by medial preoptic stimulation in female rats blocked with pentobarbital, morphine, chlorpromazine, or atropine. Everett, JW; Tyrey, L, 1982)	0.66
" This insensitivity to morphine satisfied the two pharmacological criteria for tolerance: a parallel shift to the right in the morphine dose-response curve and a reduced effect of the drug at the same brain concentration."	( Development of tolerance to the effects of morphine on luteinizing hormone secretion as a function of castration in the male rat. Cicero, TJ; Meyer, ER; Schmoeker, PF, 1982)	0.84
"The changes in effects on motor activity of rats upon repeated (48 day) dosing with four narcotic analgesics were determined."	( Motility response of rats to chronic constant-dose treatment with narcotics. Davis, WM; Hemnani, KL; Pace, HB, 1982)	0.26
" In either type of experiment the dose-response lines of naloxone against caerulein were very shallow as compared with those against morphine."	( Caerulein and morphine: an attempt to differentiate their antinociceptive effects. Zetler, G, 1982)	0.83
" Buprenorphine showed naloxone-sensitive effects with a bell-shaped dose-response curve in the thermal test but dose-dependent activity in the pressure test."	( Involvement of the median raphe nucleus in antinociception induced by morphine, buprenorphine and tilidine in the rat. Bryant, RM; Olley, JE; Tyers, MB, 1982)	0.5
" The dose-response and naloxone antagonism studies suggest that the receptor mechanisms which may subserve opiate convulsions differ from those mediating either analgesia or depressant lethality."	( Heroin: analgesia, toxicity and disposition in the mouse. Inturrisi, CE; Umans, JG, 1982)	0.26
" By dosing plasmatic neurophysins, a selective loss of the osmoreceptor function was demonstrated."	( [Chronic hypernatremia. A study of plasma neurophysins and action of morphine]. Deschepper, C; Ducobu, J; Dupont, P; Legros, JJ; Smitz, S, )	0.37
"The dose-response relationships for morphine analgesia were studied in morphine-tolerant and non-tolerant rats using two pain tests: the tail-flick test which measures the threshold for an escape response, and the formalin test which assesses the behavioral response to continuous pain generated in injured tissue."	( Morphine analgesia and tolerance in the tail-flick and formalin tests: dose-response relationships. Abbott, FV; Leber, BF; Melzack, R, 1982)	1.98
" Although there was no significant difference in the efficacy of the three doses, increasing dosage increased the average duration of analgesia provided by the drug (4 mg--593 min; 6 mg--772 min; 8 mg--885 min)."	( Dose-effect relationships of extradural morphine. Pybus, DA; Torda, TA, 1982)	0.53
" 2 The dose-response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan greater than morphine greater than Met-enkephalin greater than nalorphine greater than pentazocine."	( Pharmacological characterization of opiate physical dependence in the isolated ileum of the guinea-pig. Luján, M; Rodríguez, R, 1981)	0.45
" 3 Hemicholinium-3 (HC-3) caused a rightward shift of the dose-response curve to DL-muscarine on the ileal longitudinal muscle of the guinea-pig ileum."	( Mechanism of action of muscarine on the longitudinal muscle of the guinea-pig isolated ileum. Ochillo, RF; Tsai, CS; Tsai, MH, 1981)	0.26
" The patterns of analgesia were similar and without indication of increasing dosage requirements with time."	( The study of analgesics following single and repeated doses. Johnson, RP; Robinson, N; Waite, E; Wang, RI, )	0.13
"3 Pretreatment of the mice with naloxone caused a dose-dependent shift to the right of the dose-response curve to morphine."	( Evidence for an action of morphine and the enkephalins on sensory nerve endings in the mouse peritoneum. Bentley, GA; Newton, SH; Starr, J, 1981)	0.77
"Diacetylmorphine (DAM) and 6-acetylmorphine (AM) exhibit virtually identical dose-response and time-action profiles in studies in antinociceptive, excitatory, antidiarrheal and antidiuretic activity after subcutaneous administration to mice."	( Pharmacodynamics of subcutaneously administered diacetylmorphine, 6-acetylmorphine and morphine in mice. Inturrisi, CE; Umans, JG, 1981)	0.94
" The reduced dosage of local anaesthetic improves neonatal status and reduces the necessity of extractional aids."	( [Epidural morphine as adjunct to epidural anaesthesia in obstetrics (author's transl)]. Börner, U; Brähler, A; Hempelmann, G; Müller, H; Stoyanov, M, 1981)	0.67
" Pooled data from all patients produced a dose-response curve asymptotic by 8 mg."	( Analgesic responses to morphine and placebo in individuals with postoperative pain. Fields, HL; Gordon, NC; Levine, JD; Smith, R, 1981)	0.57
" Serum luteinising hormone (LH) and testosterone concentrations and the weight and morphology of testes, pituitary glands and secondary sex organs were examined after 4 and 9 weeks' morphine treatment and also 13 weeks after dosing stopped."	( Effects of morphine sulphate on pituitary-testicular morphology of rats. Crook, D; Heywood, R; James, RW, 1980)	0.84
" The dose-response curves for dopamine before morphine application and in its presence indicate a noncompetitive mechanism of interaction between morphine and dopamine."	( [Naloxone-dependent morphine reduction of excitatory responses of mollusk neurons to dopamine]. Bezrukova, LV; Solntseva, EI, 1981)	0.84
" 75 of these catheters were evaluated according to morphine dosage and effect."	( [Epidural morphine analgesia (PMA). III. Cancer pain (author's transl)]. Hüsch, M; Piepenbrock, S; Schappler-Scheele, B; Zenz, M, 1981)	0.92
" The dose-response curves of the naloxone group were shifted to the right of those for the saline group."	( Time course of antagonism of morphine antinociception by intracerebroventricularly administered naloxone in the rat. Cowan, A; Porreca, F; Tallarida, RJ, 1981)	0.55
" Reports of high intrabiliary pressures and bizarre cholangiograms for patients under such anesthesia led us to investigate the specific effects on intrabiliary pressure of morphine sulfate, fentanyl and butorphanol tartrate, each at two different dosage levels."	( Effects of butorphanol, fentanyl and morphine on the intrabiliary pressure of guinea pigs. Aldrete, JA; Franatovic, Y; Romo-Salas, F, 1980)	0.73
" For neurons exhibiting each of these three patterns, the mean T100, a modification of the T50 which is analogous to a dose-response curve, correlated with the effects of the drugs on evoked firing."	( Morphine and methionine-enkephalin: different effects on spontaneous and evoked neuronal firing in the mesencephalic reticular formation of the rat. Haigler, HJ; Hosford, DA, 1980)	1.7
"Intramuscular injection of staphylococcal enterotoxin B (SEB) at a dosage level of 50 microgram/kg of body weight caused death in Dutch rabbits."	( Modification of lethality induced by staphylococcal enterotoxin B in Dutch rabbits. Liu, CT; Sanders, RP, 1980)	0.26
"A new dosage form was designed whereby a polymeric silicone elastomer provided sustained delivery of morphine to mice over 11 days."	( Polydimethylsiloxane pellets for sustained delivery of morphine in mice. Anderson, JA; McGinity, JW; Riffee, WH; Wilcox, RE, 1980)	0.72
" naloxone produced a dose-dependent rightward shifting of the morphine dose-response lines, the shift produced by the 10-micrograms dose being sufficient to abolish the analgetic action of morphine doses as large as 75 mg/kg."	( Sites of antinociceptive action of systemically injected morphine: involvement of supraspinal loci as revealed by intracerebroventricular injection of naloxone. Rudy, TA; Yeung, JC, 1980)	0.75
"Cumulative dose-response curves have been widely used in many areas of pharmacology."	( Cumulative dose-response curves in behavioral pharmacology. Wenger, GR, 1980)	0.26
" Consistently, 8 days after sciatic nerve ligation but not after a sham operation, an approximately 6-fold rightward shift occurred in the morphine antinociceptive dose-response curve."	( Experimental mononeuropathy reduces the antinociceptive effects of morphine: implications for common intracellular mechanisms involved in morphine tolerance and neuropathic pain. Mao, J; Mayer, DJ; Price, DD, 1995)	0.73
" The Cmax values of the active metabolite morphine-6-glucuronide (M6G), measured in 6 of the patients, for the 3 dosing intervals followed a similar trend to the parent drug, but only doses 1 and 2 differed significantly."	( Chronopharmacokinetic variability in plasma morphine concentrations following oral doses of morphine solution. Cherry, DA; Gourlay, GK; Plummer, JL, 1995)	0.82
"Antinociceptive tolerance to morphine (MOR) was induced in groups of Sprague-Dawley rats receiving continuous intravenous infusions of morphine sulphate administered by 3 different MOR dosing regimes."	( Morphine-3-glucuronide: evidence to support its putative role in the development of tolerance to the antinociceptive effects of morphine in the rat. Smith, GD; Smith, MT, 1995)	2.03
" We conclude that morphine is clinically effective in the peripheral nervous system at this dosage range."	( Morphine/prilocaine combination for intravenous regional anesthesia. Aktürk, G; Dohman, D; Erciyes, N; Solak, M, 1995)	2.07
" administration of 5 mg/kg morphine, a mu-opioid agonist, or U50488H (U50), a kappa 1-opioid agonist, for 5 days in male CD-1 mice results in a 2-3-fold shift to the right of the respective analgesic (tail flick) dose-response curves, indicating the development of tolerance."	( The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the mu-opioid morphine but not to kappa opioids. Elliott, K; Inturrisi, CE; Kolesnikov, YA; Minami, N; Pasternak, GW, 1994)	0.78
" Administration of L-arginine alone for 3-10 days shifts morphine's dose-response curve over 2-fold to the right while D-arginine is without effect, as is daily administration of L-arginine along with the NOS inhibitor NOArg."	( Nitric oxide and opioid tolerance. Babey, AM; Cheng, J; Inturrisi, CE; Kolesnikov, Y; Pasternak, GW; Trifilletti, RR, 1994)	0.53
"Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management."	( Control of severe pain in children with terminal malignancy. Berde, CB; Collins, JJ; Grier, HE; Kinney, HC, 1995)	0.29
") produced a significant rightward shift of the dose-response curve of morphine, levorphanol, methadone, pilocarpine, clonidine and tizanidine; a modest, but not statistically significant, rightward shift of the dose-response curves of the mu-selective peptides DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin) and PL017 ([N-Me-Phe3,D-Pro4]-morphiceptin); and no shift of the dose-response curves of alfentanil, carfentanil, fentanyl, sufentanil, or beta-endorphin."	( The 'glibenclamide-shift' of centrally-acting antinociceptive agents in mice. Martinez, RP; Raffa, RB, 1995)	0.52
" The overall frequency and severity of adverse events did not differ between the two dosing schedules."	( Control of cancer-related pain with MS Contin: a comparison between 12-hourly and 8-hourly administration. Harsanyi, Z; Latreille, J; Lemire, F; Mignault, GG; Richer, P; Stewart, JH; Viguié, F, 1995)	0.29
" By contrast, morphine treatment during hibernation resulted in significantly reduced abstinence compared with that observed after treatment during the NH state, with no significant morphine dose-response or duration-response trends evident."	( Quantitative and qualitative aspects of the hibernation-related reduction of morphine physical dependence in the ground squirrel (Citellus lateralis). Beaver, TA; Beckman, AL; Lewis, FC; Newman, JR, 1995)	0.88
"An intermittent intake of low-dose droperidol with morphine given via a PCA delivery system in two treatment groups gave evidence for a dose-response relation between the amount of droperidol added and the proportion of patients needing a rescue antiemetic."	( Antiemetic efficacy of a droperidol-morphine combination in patient-controlled analgesia. Bach, T; Jackson, D; McKenzie, R; Riley, T; Tantisira, B, 1995)	0.82
", the morphine dose-response curve shifted to the left and the ED50 value of morphine decreased."	( Effects of a highly selective nonpeptide delta opioid receptor agonist, TAN-67, on morphine-induced antinociception in mice. Endoh, T; Misawa, M; Mori, T; Nagase, H; Suzuki, T; Tsuji, M, 1995)	1
" A treatment plan was developed consisting of a low-dose morphine infusion with increasing dosage until pain was relieved."	( Successful treatment of painful crises of Fabry disease with low dose morphine. Finley, GA; Gordon, KE; Ludman, MD, 1995)	0.77
"The aim of this prospective study was to evaluate the efficacy of two dosage regimens of (i."	( Can immediate opioid requirements in the post-anaesthesia care unit be used to determine analgesic requirements on the ward? Butscher, K; Mazoit, JX; Samii, K, 1995)	0.29
" Dose-response curves for hot plate and tail immersion tests were established for IT neostigmine, physostigmine, and echothiophate in rats."	( Intrathecal acetyl cholinesterase inhibitors produce analgesia that is synergistic with morphine and clonidine in rats. Abram, SE; Winne, RP, 1995)	0.51
" The first dose of naltrexone was given 24 hours before MSC dosing, followed by a second dose at the time of MSC dosing and a third dose 24 hours after MSC administration."	( A bioequivalence study of oral controlled-release morphine using naltrexone blockade. Goldenheim, PD; Grandy, RP; Kaiko, RF; Reder, RF; Sackler, RS, 1995)	0.54
" Dose-response analysis showed a smaller (26%), non-significant, increase at a lower dose of 2 mg kg-1 and no effect at a higher dose of 40 mg kg-1."	( Microdialysis reveals a morphine-induced increase in pallidal opioid peptide release. Bertolucci, M; Evans, CJ; Maidment, NT; Olive, MF, 1995)	0.6
" Dose-response curves were subsequently determined under conditions of no stress, restraint, corticosterone (3 mg/kg, IP), and saline."	( Effects of restraint stress and intra-ventral tegmental area injections of morphine and methyl naltrexone on the discriminative stimulus effects of heroin in the rat. Shaham, Y; Stewart, J, )	0.36
" Bicuculline (GABAA receptor antagonist) and picrotoxin (chloride ion channel blocker) given intrathecally produced rightward shifts in the dose-response curves of DPDPE and heroin given intracerebroventricularly."	( Spinal GABA receptors mediate brain delta opioid analgesia in Swiss Webster mice. Fujimoto, JM; Rady, JJ, 1995)	0.29
" Dose-response and time course curves for the analgesic effect of morphine (1."	( Rat strain differences in the potentiation of morphine-induced analgesia by stress. Holtzman, SG; Woolfolk, DR, 1995)	0.79
" pretreatment (25 min) with morphine sulfate, 8-OH-DPAT, buspirone and 5-CT shifted the morphine sulfate dose-response curve 3- to 5-fold to the right."	( Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice. Alhaider, AA; Wilcox, GL, 1993)	0.58
" A single NO2Arg dose retards morphine tolerance for several days, and dosing every 4 days is almost as effective as daily NO2Arg."	( Blockade of tolerance to morphine but not to kappa opioids by a nitric oxide synthase inhibitor. Ciszewska, G; Kolesnikov, YA; Pasternak, GW; Pick, CG, 1993)	0.88
" These data suggest a dose-response relation between the magnitude of prenatal cocaine exposure and impaired fetal growth."	( Relation between meconium concentration of the cocaine metabolite benzoylecgonine and fetal growth. Cabral, H; Frank, DA; Mirochnick, M; Turner, A; Zuckerman, B, 1995)	0.29
"Tolerance to the antinociceptive (analgesic) effect of morphine, a mu-opioid agonist, was developed in male CD-1 mice as assessed by a shift to the right of the analgesic (tail-flick) dose-response curves and an increase in the ED50 values."	( Dextromethorphan attenuates and reverses analgesic tolerance to morphine. Elliott, K; Hynansky, A; Inturrisi, CE, 1994)	0.77
" The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation."	( Continuous midazolam infusion for the management of morphine-induced myoclonus. Adams, VR; Chavez, CM; Duncan, MH; Holdsworth, MT; Vaughan, LJ, 1995)	0.79
" If further dosage increase of morphine are necessary in this setting, increases in the midazolam infusion also may be required."	( Continuous midazolam infusion for the management of morphine-induced myoclonus. Adams, VR; Chavez, CM; Duncan, MH; Holdsworth, MT; Vaughan, LJ, 1995)	0.83
" The dose-response curves of [Lys7]dermorphin antinociception were shifted to the right by the pretreatment with naloxone (0."	( Production of antinociception by peripheral administration of [Lys7]dermorphin, a naturally occurring peptide with high affinity for mu-opioid receptors. Lattanzi, R; Melchiorri, P; Negri, L, 1995)	0.29
" We have further investigated the non-opioid nature of this activity by comparing the efficacies of dyn A(1-13) and (2-17) under different experimental protocols with a variety of dosing regimens."	( Dynorphin A modulates acute and chronic opioid effects. He, L; Hooke, LP; Lee, NM, 1995)	0.29
" To examine the properties of various pain rating methods we established dose-response relations for formalin injected in the plantar surface of one hind paw, and the analgesic effects of morphine and amphetamine using the most frequently reported behavioural measures of pain (favouring, lifting, licking and flinching/shaking of the injured paw) and combinations of these."	( The formalin test: scoring properties of the first and second phases of the pain response in rats. Abbott, FV; Franklin, KBJ; Westbrook, FR, 1995)	0.48
" Morphine, pethidine and fentanyl, which showed a biphasic dose-response relationship with respect to seizure modulation, abolished the anticonvulsant activity of propofol to exhibit their own intrinsic activity in proconvulsant doses."	( Interactions between opioid drugs and propofol in laboratory models of seizures. Ahmad, I; Pleuvry, BJ, 1995)	1.2
"The randomized, double-blind, dose-response study was designed to evaluate the effects of the addition of clonidine to epidural morphine on postoperative analgesia and side effects in patients undergoing cesarean delivery."	( Addition of clonidine to epidural morphine enhances postoperative analgesia after cesarean delivery. Capogna, G; Celleno, D; Costantino, P; Foresta, S; Zangrillo, A, )	0.62
" However, the effect of differences in dosing protocol on tolerance to opioid analgesics of high or low efficacy has not been addressed."	( The effect of intrinsic efficacy on opioid tolerance. Duttaroy, A; Yoburn, BC, 1995)	0.29
" At the end of treatment, the pumps and placebos were removed, and 4-24 h later, mice were tested in dose-response studies (tail flick) using the same drug that had been chronically administered."	( The effect of intrinsic efficacy on opioid tolerance. Duttaroy, A; Yoburn, BC, 1995)	0.29
"5 micrograms), parallel rightward shifts of both morphine and RB 101 (mixed enkephalin-degrading-enzyme inhibitor) dose-response curves, were observed, but the concentration of beta-FNA required to reduce the analgesic responses was about 10 times higher for RB 101 (0."	( Assessment of endogenous enkephalins efficacy in the hot plate test in mice: comparative study with morphine. Noble, F; Roques, BP, 1995)	0.76
" The five opioid peptides induced no changes in the dose-response curves with isoproterenol and forskolin."	( Effects of opioid substances on cAMP response to the beta-adrenergic agonist isoproterenol in human mononuclear leukocytes. Ioverno, A; Lotti, G; Musso, NR; Pende, A; Vergassola, C, 1995)	0.29
" Pretreatment with morphine (3 nmol, -140 min) produced acute antinociceptive tolerance as demonstrated by a 45-fold rightward shift of the morphine dose-response curve."	( Preventing morphine antinociceptive tolerance by irreversible mu opioid antagonists before the onset of their antagonism. Archer, S; Bidlack, JM; Jiang, Q; Sebastian, A; Seyed-Mozaffari, A, 1995)	1.01
" This shift in the cocaine dose-response curve was apparent when conditioning commenced either 3 or 7, but not 14, days after the cessation of cocaine pretreatment."	( Sensitization to the conditioned rewarding effects of cocaine: pharmacological and temporal characteristics. Heidbreder, C; Shippenberg, TS, 1995)	0.29
" Increasing the stimulus intensity was associated with a shift of the dose-response curve to the right, without a change of slope."	( Effects of intravenous morphine and buprenorphine on a C-fiber reflex in the rat. Chauvin, M; Guirimand, F; Le Bars, D; Willer, JC, 1995)	0.6
" Twenty-seven-, 20- and 15-day-old rats all developed tolerance as indicated by a rightward shift of the dose-response curve after chronic morphine."	( The ontogeny of mu opiate tolerance and dependence in the rat: antinociceptive and biochemical studies. Kuhn, CM; Little, PJ; Windh, RT, 1995)	0.49
" At the spinal level, the dose-response curves for peak effect and area under the curve for morphine were shifted to the left (indicating potentiation) by a submaximal dose of intrathecal (i."	( The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats. Hayashi, T; Hill, HF; Luger, TJ; Weiss, CG, 1995)	0.51
" Patient charts were reviewed to collect the following data: patient's age, weight, dosage schedule, concurrent sedatives, ventilatory status, whether adequacy of analgesia was documented, and descriptions of adverse drug reactions (ADRs)."	( Morphine use and adverse effects in a neonatal intensive care unit. Myers, TF; Sajous, CH; Tholl, DA; Wager, MS, 1994)	1.73
" In terms of butorphanol and morphine tolerance, a parallel rightward shift in the dose-response curve was produced with the degree of shift proportional to the log of the infusion dose."	( Tolerance development to butorphanol: comparison with morphine. Feng, YZ; Ho, IK; Hoskins, B; Jaw, SP; Tseng, YT, 1994)	0.83
" Continuous ICV infusion with butorphanol produced a marked rightward shift of the antinociceptive dose-response curve resulting from U-50,488 challenge."	( Crosstolerance between butorphanol and morphine in rats. Feng, YZ; Ho, IK; Hoskins, B; Narita, M; Tseng, YT, 1994)	0.56
" Mice were injected intracerebroventricularly (ICV), or intrathecally (IT), or IT and ICV with PTX, and dose-response studies of the antinociceptive action of systemic (SC) morphine, fentanyl, and etorphine were conducted 10 days later."	( Spinal and supraspinal effects of pertussis toxin on opioid analgesia. Davis, T; Duttaroy, A; Shah, S; Yoburn, BC, 1994)	0.48
" The test proved sensitive to the effects of barbiturates and benzodiazepines which produced graded dose-response functions."	( A pharmacological evaluation of the pull-up test for muscle relaxation in rats. Meert, TF; Shephard, RA; Wilson, NE, 1993)	0.29
" Pain scores, frequency of medication, and total dosage of medication were recorded in the immediate postoperative period."	( Postoperative pain following outpatient pediatric urologic surgery: a comparison of anesthetic techniques. Goldberger, N; Hochman, HI; Londergan, TA, 1994)	0.29
" The prescribed and administered mean dosages were less than the minimum recommended dosage for morphine."	( Postoperative pain management in preverbal children: the prescription and administration of analgesics with and without caudal analgesia. Altimier, L; Dick, MJ; Holditch-Davis, D; Lawless, S; Norwood, S, 1994)	0.51
"A method of accelerated titration of morphine dosage is described."	( Accelerated titration of morphine for rapid relief of cancer pain. Lichter, I, 1994)	0.86
" In addition, opioid dose-response curves with preemptive administration were compared with early and late postadministrations."	( Electrophysiologic analysis of preemptive effects of spinal opioids on N-methyl-D-aspartate receptor-mediated events. Chapman, V; Dickenson, AH; Haley, JE, 1994)	0.29
" With the use of the tail flick model, dose-response curves were constructed to codeine, morphine, oxycodone and oxymorphone (the O-demethylated metabolite of oxycodone) in both rat strains."	( The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model. Bochner, F; Cleary, J; Mikus, G; Somogyi, A, 1994)	0.51
"The pressor response to noxious colorectal distention (80 mmHg, 20 s) was evaluated in 29 male Sprague-Dawley rats and dose-response curves were determined for intravenous morphine, ketorolac and the mixture of morphine and ketorolac."	( Ketorolac potentiates morphine antinociception during visceral nociception in the rat. Gebhart, GF; Maves, TJ; Meller, ST; Pechman, PS, 1994)	0.8
" In the physical dependence test, nefiracetam and codeine phosphate were administered to rats mixed with food for 43 days in a gradually increasing dosage schedule, followed by feeding a drug-free normal diet to detect signs of withdrawal."	( Drug dependence study of the new cognition-enhancing agent nefiracetam in rats. Akiyama, Y; Fujikawa, K; Takayama, S, 1994)	0.29
" Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content."	( The effect of morphine on the biosynthesis of catecholamines in the rat brain. Kwan, TK; Malini, M; Perumal, R, 1994)	0.94
"5 to 37 fold) to the right of the dose-response curve for clonidine without significant change of maximum inhibitory effect, in a manner compatible with competitive antagonism (ED50B = 29."	( Modulation by central postsynaptic alpha 2-adrenoceptors of the jaw-opening reflex induced by orofacial stimulation in rats. Barturen, F; García-Sevilla, JA; García-Vallejo, P, 1994)	0.29
" Ketamine (1, 5, 10 and 20 mg/kg) showed relatively weak antinociceptive effects with no apparent dose-response relationship."	( Antinociceptive effects of ketamine-opioid combinations in the mouse tail flick test. Dambisya, YM; Lee, TL, 1994)	0.29
" Subsequent dose-response studies across a somewhat lower dose range using equimolar doses of morphine and M6G (3-80 mumoles/kg) found that both drugs significantly increased locomotor activity beginning at 20 mumoles/kg."	( Morphine-6-glucuronide: a potent stimulator of locomotor activity in mice. Alkana, RL; Jones, BL; Mørland, J; Palomares, ML, 1994)	1.95
"3 mg/kg) which shifted the dose-response curve to the right."	( An investigation into the discriminative stimulus and reinforcing properties of the CCKB-receptor antagonist, L-365,260 in rats. Bentley, G; Bourson, A; Hargreaves, R; Iversen, S; Jackson, A; Rycroft, W; Tattersall, D; Tricklebank, M, 1994)	0.29
" Dosage patterns were individualized."	( Intraspinal delivery of opiates by an implantable, programmable pump in patients with chronic, intractable pain of nonmalignant origin. Kanoff, RB, 1994)	0.29
" The following were taken as evaluation criteria: age, sex, performance status, duration and dosage of previous systemic and current spinal morphine therapy, concomitant analgesic and co-analgesic medication, pretreatment of the dorsal column and neurological dysfunction due to damage either of the nerval plexus or of the medulla spinalis."	( Complications of spinal opioid therapy: myoclonus, spastic muscle tone and spinal jerking. Bingel, U; Kloke, M; Seeber, S, 1994)	0.49
" The observation parameters included plasma leucine enkephalin (LEK), postoperative total dosage of narcotics administered for 5 days, VAS for pain and pain reliever, abdominal distension, urinary retention, constipation, etc."	( Combined traditional Chinese medicine and Western medicine. Relieving effects of Chinese herbs, ear-acupuncture and epidural morphine on postoperative pain in liver cancer. Cao, SH; Gan, YH; Li, QS; Lu, JZ; Ma, HJ; Xie, GM; Zhang, ZH, 1994)	0.49
"Randomized, double-blind, placebo-controlled, dose-response evaluation."	( Intravenous ketorolac as an adjunct to patient-controlled analgesia (PCA) for management of postgynecologic surgical pain. Paige, D; Sevarino, FB; Silverman, DG; Sinatra, RS, )	0.13
" The different temporospatial pattern of immediate early gene expression in neurons of the spinal cord dorsal horn following noxious stimulation suggest that variable transcription complexes may interact with DNA regulatory sequences and could thus activate alternative secondary response genes, even under protection of a high dosage of morphine applied before noxious stimulation."	( Application of morphine prior to noxious stimulation differentially modulates expression of Fos, Jun and Krox-24 proteins in rat spinal cord neurons. Bravo, R; Herdegen, T; Schadrack, J; Tölle, TR; Zieglgänsberger, W; Zimmermann, M, 1994)	0.81
" A bell-shaped dose-response curve was observed for the priming effect of morphine; maximal enhancement of TNF-alpha release (310 +/- 15% of control) was detected at a concentration of 10(-10) M morphine."	( Priming effect of morphine on the production of tumor necrosis factor-alpha by microglia: implications in respiratory burst activity and human immunodeficiency virus-1 expression. Chao, CC; Gekker, G; Hu, S; Peterson, PK; Sheng, WS; Tsang, M, 1994)	0.85
" produced an acute rightward shift of the dose-response curves of the selective mu opioid agonists alfentanil and morphine at all tested temperatures."	( In vivo determination of mu opioid receptor turnover in rhesus monkeys after irreversible blockade with clocinnamox. Butelman, ER; Lewis, JW; Walker, EA; Woods, JH; Zernig, G, 1994)	0.5
"This double-blind randomised study compared the analgesic efficacy, respiratory effects, side effects, and pharmacokinetic disposition of 24 hr lumbar epidural and intravenous infusions of the same dosage regimen of fentanyl (1."	( A comparison of lumbar epidural and intravenous fentanyl infusions for post-thoracotomy analgesia. Baxter, AD; Goernert, L; Hull, K; Laganière, S; Samson, B; Stewart, J, 1994)	0.29
" The prolonged release of MS-CR makes the MS-CR a good choice in the management of pain in patients with burns on an 8- to 12-hour dosing schedule, even though the patient might exhibit an increased clearance."	( Pharmacokinetics of morphine sulfate in patients with burns. Herman, RA; Kealey, GP; Komorowski, J; Miotto, J; Veng-Pedersen, P, )	0.45
" The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml-1 after third molar surgery."	( The efficacy of locally applied morphine in post-operative pain after bilateral third molar surgery. Gilroy, J; Moore, UJ; Rawlins, MD; Seymour, RA, 1994)	0.83
" Therefore, we prospectively determined the dose-response relationship and the minimum effective combination dose of epidural morphine and fentanyl (fentanyl given after morphine) for posthysterectomy analgesia."	( Minimum effective combination dose of epidural morphine and fentanyl for posthysterectomy analgesia: a randomized, prospective, double-blind study. Akiyoshi, Y; Ashimura, H; Naito, H; Nishijima, Y; Sato, S; Tanaka, M; Watanabe, S, 1993)	0.75
") induced a parallel displacement to the right of the morphine dose-response curve."	( Gliquidone, an ATP-dependent K+ channel antagonist, antagonizes morphine-induced hypermotility. Baeyens, JM; Del Pozo, E; Ocaña, M, 1993)	0.77
" morphine dose-response curve in mice exposed to CWSS was displaced significantly to the left when compared to that obtained in control (i."	( Modulation of morphine antinociception by swim-stress in the mouse: involvement of supraspinal opioid delta-2 receptors. Bowen, WD; Hruby, VJ; Mosberg, HI; Porreca, F; Portoghese, PS; Sultana, M; Takemori, AE; Vanderah, TW; Wild, KD, 1993)	1.56
" Dose-response curves for the enhancement of the two drugs on morphine analgesia were bell-shaped."	( [Potentiation of morphine- and ohmefentanyl-induced analgesia by cholecystokinin receptor antagonists in rat]. Han, JS; Sun, YH; Zhou, Y, 1993)	0.87
" Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO."	( Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Barker, G; Bohn, D; Dagan, O; Gruenwald, C; Klein, J; Koren, G, 1993)	0.29
" In addition to fixed combinations, inclusion of a low morphine dose in one region shifts the analgesic dose-response curves in the others."	( Synergistic brainstem interactions for morphine analgesia. Bodnar, RJ; Pasternak, GW; Rossi, GC, 1993)	0.8
" Tolerance development was assessed by evaluating dose-response curves to the analgesic effects of morphine on the tail-flick test."	( Morphine as a cue in associative tolerance to morphine's analgesic effects. Cepeda-Benito, A; Tiffany, ST, 1993)	1.95
" These data suggest that this new formulation of morphine is equipotent to conventional controlled-release morphine tablets and provides pain relief for a 12-hour dosing interval."	( A novel morphine sulphate preparation: clinical trial of a controlled-release morphine suspension in cancer pain. Forman, WB; Hunt, C; Kush, R; Portenoy, RK; Shepard, K; Yanagihara, RH, 1993)	0.97
" Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration."	( Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity. Alastra, AJ; Cohen, C; Goldberg, SR; Marley, RJ; Sannerud, CA; Serdikoff, SL, 1993)	0.29
" Both morphine and amphetamine shifted the dose-response curve for nicotine down and to the left, indicating increased efficacy and potency, respectively."	( Nicotine and brain-stimulation reward: interactions with morphine, amphetamine and pimozide. Huston-Lyons, D; Kornetsky, C; Sarkar, M, 1993)	1.01
" Bupivacaine-induced side effects were absent below a daily dosage of 30 mg by continuous infusion."	( Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of cancer pain: a retrospective analysis of 51 cases. Crul, BJP; De Bock, M; Van Dongen, RTM, 1993)	0.57
" TRH significantly potentiated the magnitude and duration of both morphine antinociception and hyperthermia in both anterior and posterior PAG placements, and shifted mesencephalic morphine's antinociceptive dose-response curve significantly to the left."	( Site-specific modulation of morphine and swim-induced antinociception following thyrotropin-releasing hormone in the rat periaqueductal gray. Bodnar, RJ; Robertson, JA, 1993)	0.82
" Estimated ED50 from the dose-response curves for morphine and morphine-6-glucuronide showed about a 30 times more potent antinociceptive effect of morphine-6-glucuronide compared with morphine."	( Intrathecal morphine-3-glucuronide does not antagonize spinal antinociception by morphine or morphine-6-glucuronide in rats. Kalso, E; Rosenberg, PH; Suzuki, N, 1993)	0.92
"This study compares several dosing regimens for patient-controlled analgesia (PCA) in the management of acute maxillofacial surgical pain."	( Patient-controlled analgesia: a comparison of dosing regimens for acute postsurgical pain. Edwards, RC; Foley, WL; Jacobs, LF, 1994)	0.29
" A randomized, placebo-controlled study comparing the time-action, dose-response and potency of the respiratory effects of M6G to morphine was done using a nonanesthetized neonatal guinea pig model and a noninvasive computerized plethysmograph technique."	( Morphine-6-beta-D-glucuronide respiratory pharmacodynamics in the neonatal guinea pig. Murphey, LJ; Olsen, GD, 1994)	1.94
" In the present study we used an experimental tolerance paradigm using morphine pellets (75 mg) to produce an 1-fold shift in the morphine dose-response curve in rats."	( Modulation of morphine tolerance by the competitive N-methyl-D-aspartate receptor antagonist LY274614: assessment of opioid receptor changes. Cheng, J; Inturrisi, CE; Pasternak, GW; Tiseo, PJ, 1994)	0.88
" The results strongly recommend extensive application of EA in postoperative care, so as to decrease both the required dosage of morphine and the subsequent occurrence of postoperative ileus, while attaining sufficient analgesia."	( Electroacupuncture reversed the inhibition of intestinal peristalsis induced by intrathecal injection of morphine in rabbits. Dai, JL; Fu, ZM; Ren, ZJ; Xu, SF; Zhu, YH, 1993)	0.71
" Inadequate information exists delineating ITMS respiratory effects in the dosage range most frequently employed today."	( Dose-response pharmacology of intrathecal morphine in human volunteers. Bailey, PL; Foster, W; Lu, JK; Pace, NL; Rhondeau, S; Schafer, PG; Stanley, TH; Timmins, BS, 1993)	0.55
"To determine the influence of stimulation intensity on dose-response curves of three analgesics in halothane-anesthetized rats, continued immersion of the tail in 52."	( Suppression of nociceptive responses by spinal mu opioid agonists: effects of stimulus intensity and agonist efficacy. Saeki, S; Yaksh, TL, 1993)	0.29
"To report a case of high transdermal fentanyl dosage requirements in a patient with chronic cancer pain."	( High transdermal fentanyl requirements in a patient with chronic cancer pain. Lehr, VT; Renaud, EA, 1993)	0.29
" Transdermal fentanyl therapy was initiated on hospital day 1 at 100 micrograms/h and the MS continuous intravenous infusion dosage was increased."	( High transdermal fentanyl requirements in a patient with chronic cancer pain. Lehr, VT; Renaud, EA, 1993)	0.29
"This patient's high transdermal fentanyl dosage requirement was related to disease progression."	( High transdermal fentanyl requirements in a patient with chronic cancer pain. Lehr, VT; Renaud, EA, 1993)	0.29
" The primary physician was allowed to titrate the dosage as required to meet the patient's requirement for analgesia."	( Relationship between pain severity and serum beta-endorphin levels in postoperative patients. Asher, MA; Klem, SA; Leff, RD; Leonard, TM; Rapoff, MA, )	0.13
"A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0."	( The medullary dorsal horn. A site of action of morphine in producing facial scratching in monkeys. Dubner, R; Iwata, K; Kenshalo, DR; Thomas, DA; Williams, GM, 1993)	0.77
" This study demonstrates that the hollow-type suppository containing powdered morphine is a more effective rectal dosage vehicle than the conventional suppository."	( Difference in rectal absorption of morphine from hollow-type and conventional suppositories in rabbits. Matsumoto, M; Matsumoto, Y; Watanabe, Y; Yamamoto, I, 1993)	0.79
" In both tests KT had a poor analgesic effect without dose-response relationships."	( Ketorolac tromethamine: an experimental study of its analgesic effects in the rat. Bustamante, D; Paeile, C, 1993)	0.29
" In groups II and III, 43% of the patients needed an increase of the morphine dosage during therapy."	( [Morphine tablets for chronic non-tumor-induced pain. Which factors modify the success or failure of a long-term therapy?]. Gleim, M; Maier, C; Schulzeck, S, 1993)	1.43
" Both devazepide and L-365,260 showed a bell-shaped dose-response curve."	( Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord. Han, JS; Sun, YH; Zhang, ZW; Zhou, Y, 1993)	0.52
" These results suggest a 50% reduction in morphine dosage in children requiring inotropic support following cardiac surgery."	( Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support. Barker, G; Bohn, D; Dagan, O; Klein, J; Koren, G, 1993)	1.99
"A randomized, placebo-controlled, double-blind clinical trial was conducted to compare the use of regularly dosed po morphine and on-demand in morphine in 47 patients undergoing total hip arthroplasty."	( A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of postsurgical pain. Glick, N; Levine, M; McCormack, JP; Warriner, CB, 1993)	0.77
" Thus, epidural BUP-MS appears to provide adequate postoperative analgesia while preventing withdrawal in opioid-dependent patients, if three times the normal dosage and duration of therapy are employed."	( A comparison of postoperative epidural analgesia between patients with chronic cancer taking high doses of oral opioids versus opioid-naive patients. Bacon, DR; de Leon-Casasola, OA; Donaparthi, S; Lema, MJ; Myers, DP; Peppriell, J; Rempel, J, 1993)	0.29
" Dose-response curves for pentobarbital given alone and in combination with morphine were determined (by probit analysis) separately for each of the pressure levels."	( Pentobarbital-morphine anesthetic interactions in terms of intensity of noxious stimulation required for arousal. Bradley, EL; Brown, PT; Kissin, I; Stanski, DR, 1993)	0.88
" Dose-response curves for precipitated abstinence evaluated as changes in mean arterial pressure and heart rate show a gradual increase in maximum followed by a progressive shift to the left as dependence progresses."	( Acute opioid dependence in the cardiovascular system of the spinal rat. Cruz, SL; Villarreal, JE, 1993)	0.29
" Dose-response curves showed a maximum at 10(-8) M morphine."	( Direct influence of morphine on the release of arachidonic acid and its metabolites. Mevkh, AT; Sergeeva, MG; Terentjeva, IV; Varfolomeev, SD, 1993)	0.86
"The plasma concentrations and renal clearance values of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined in 11 adult cancer patients maintained on a long term oral morphine dosage (10 to 100mg every 4h)."	( Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine. Bochner, F; Cleary, JF; Danz, C; Milne, RW; Nation, RL; Olweny, C; Somogyi, AA; Tsirgiotis, P; van Crugten, J, 1993)	0.79
" A naltrexone-insensitive component to beta-endorphin antinociception also was identified in studies which evaluated the ability of the antagonist to shift the beta-endorphin dose-response curve."	( Biochemical and pharmacological characterization of multiple beta-endorphinergic antinociceptive systems in the rat periaqueductal gray. Hawranko, AA; Monroe, PJ; Smith, DJ; Smith, DL, 1996)	0.29
" Recommendations for managing opioid-induced muscle hyperactivity include reduction of the opioid dosage and/or administration of clonazepam therapy."	( Opioid-induced muscle activity: implications for managing chronic pain. Levitt, R; Steen, PD; Sylvester, RK, 1995)	0.29
" Morphine-tolerant mice displayed a 7-fold greater ED50 for Bay K 8644 antinociception than placebo-treated animals; no difference was found in the dose-response curve for thapsigargin."	( Alterations in L-type calcium channels in the brain and spinal cord of acutely treated and morphine-tolerant mice. Bernstein, MA; Welch, SP, 1995)	1.42
" When the regenerated cellulose acetate device filled with osmotic filler was implanted in rabbits which were subsequently dosed at day 7 and day 14 post-implant with 150 mg kg(-1) morphine sulphate, the concentration of morphine in the device was only about 10-fold less than that measured in rabbit blood."	( Biocompatibility and in vivo morphine diffusion into a placebo morphine-triggered naltrexone delivery device in rabbits. Fritzinger, BK; Heller, J; Nakayama, GR; Roskos, KV; Tefft, JA, 1995)	0.77
" Average daily dosage of intrathecal morphine increased over time by approximately sevenfold."	( Intrathecal infusion systems for treatment of chronic low back and leg pain of noncancer origin. Doleys, DM; Tutak, U, 1996)	0.57
" In the present experiment, baseline nociceptive sensitivities and morphine antinociceptive dose-response relationships (0."	( Differential genetic mediation of sensitivity to morphine in genetic models of opiate antinociception: influence of nociceptive assay. Belknap, JK; Kest, B; Mogil, JS; Sadowski, B, 1996)	0.78
" The main aim of this study was to investigate the dose-response relationship of extradural infusion of ropivacaine."	( Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Hägglöf, B; Mooney, PH; Payne, J; Schug, SA; Scott, DA, 1996)	0.29
"To assess effects of stimulus intensity, dose-response curves in rats for radiant heat-evoked withdrawal of the hind paw was assessed after the intrathecal (i."	( Differential right shifts in the dose-response curve for intrathecal morphine and sufentanil as a function of stimulus intensity. Dirig, DM; Yaksh, TL, 1995)	0.53
" We conclude that a single dose of 150 mg tramadol given at the end of surgery provided postoperative analgesia equivalent to that provided by this dosage regimen of epidural morphine for the initial postoperative period."	( Intravenous tramadol versus epidural morphine for postthoracotomy pain relief: a placebo-controlled double-blind trial. Gordon, PC; Heijke, SA; James, MF, 1996)	0.76
" This information must be considered above all as a dosage adjustment tool enabling use of the two forms by application of a correction factor of the order of 15% when prescribing Skenan in comparison with Moscontin."	( Study of the bioequivalence of two controlled-release formulations of morphine. Bourget, P; Lesne-Hulin, A; Quinquis-Desmaris, V, 1995)	0.53
" Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21-25 (weanlings) and tolerance assessed by determining dose-response curves for ACTH and corticosterone secretion following an acute morphine challenge."	( Ontogenetic studies of tolerance development: effects of chronic morphine on the hypothalamic-pituitary-adrenal axis. Kuhn, CM; Little, PJ, 1995)	0.83
"1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days."	( Modulation of opioid analgesia by agmatine. Jain, S; Kolesnikov, Y; Pasternak, GW, 1996)	0.58
" These results suggest that OSR and MST are bioequivalent and that if patients were to transfer between formulations, dosage adjustment would be unnecessary, irrespective of their meal schedules or food intake."	( Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus. Aliyar, CA; Crawford, FE; Drake, J; Gibson, P; Horth, CE; Kirkpatrick, CT, 1996)	0.53
"Tolerance to morphine analgesia (tail-immersion test) was examined after manipulation of two aspects of a tolerance test: 1) the route of drug administration and 2) the time interval between the test dosing and the tolerance test."	( Loss of tolerance to morphine after a change in route of administration: control of within-session tolerance by interoceptive conditioned stimuli. Birbaumer, N; Kalant, H; Mucha, RF, 1996)	0.98
" Dose-response curves for both measures shifted rightward substantially (roughly fivefold) following chronic (daily) exposure to morphine, indicating that tolerance developed to the drug's effects."	( Acute and chronic effects of morphine in pigeons responding under a progressive-ratio schedule of food delivery. Lesage, M; Poling, A; Roe, D; Schaefer, D, 1996)	0.79
" Analgesia was measured by the tail-flick method, and tolerance levels were assessed by dose-response curve methodology."	( Unsignaled morphine delivery does not disrupt the development of associative morphine tolerance in the rat. Cepeda-Benito, A; Tiffany, ST, 1996)	0.68
" Analgesia was assessed by the tail-flick method, and tolerance was defined as the shift to the right of the dose-response curve of morphine-experienced relative to saline control animals."	( Role of drug-administration cues in the associative control of morphine tolerance in the rat. Cepeda-Benito, A; Tiffany, ST, 1995)	0.73
" Each morphine dosing level was maintained for 2 weeks, with test drugs administered during the second week of maintenance of each morphine dose."	( Buprenorphine, morphine and naloxone effects during ascending morphine maintenance in humans. Bigelow, GE; Preston, KL; Schuh, KJ; Stitzer, ML; Walsh, SL, 1996)	1.13
" A bell shaped dose-response curve was noted in the behavioural studies with respect to the interaction between L740,094 and morphine."	( L-740,093, a new antagonist of the CCK-B receptor, potentiates the antinociceptive effect of morphine: electrophysiological and behavioural studies. Hoffmann, O; Wiesenfeld-Hallin, Z; Xu, XJ, 1996)	0.72
" Patients with a 'stable and low level of cancer pain' receiving a constant dosage of sustained release morphine during a pre-study phase of 6 days were included in the study."	( Direct conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer pain. Donner, B; Strumpf, M; Tryba, M; Zenz, M, 1996)	0.8
"]) did not change tail-flick latency in control animals but produced a dose-dependent enhancement of the antinociception induced by clonidine and morphine, and shifted their dose-response curves to the left."	( Cromakalim differentially enhances antinociception induced by agonists of alpha(2)adrenoceptors, gamma-aminobutyric acid(B), mu and kappa opioid receptors. Baeyens, JM; Barrios, M; Ocaña, M, 1996)	0.49
" Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS."	( Incorporation of codeine and metabolites into hair. Role of pigmentation. Cone, EJ; Gygi, SP; Joseph, RE; Rollins, DE; Wilkins, DG, 1996)	0.5
" Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose."	( Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome. Buckley, B; Conant, M; Cundiff, D; Kaplan, R; Maciewicz, R; Ries, K; Slagle, S; Slywka, J, 1996)	1.08
" Using a multiple regression analysis, only the morphine dosage was found to be an independent prognostic factor."	( Intraventricular administration of morphine for control of intractable cancer pain in 90 patients. Foroglou, G; Fountzilas, G; Karavelis, A; Selviaridis, P, 1996)	0.83
"0 mg/kg) if the dosing interval was 10 min, whereas 30."	( Opioid antagonist profile of SC nor-binaltorphimine in the formalin paw assay. Grouhel, A; Wettstein, JG, 1996)	0.29
" Full dose-response curves were done of the effects of morphine on food intake in males and females in both rats and mice, representing the typical and atypical responses, respectively."	( Male/female comparison of morphine effect on food intake--relation to anorexia nervosa. Barnes, C; D'Amico-Rasmussen, Q; Lawhorn, J; Marrazzi, MA; McQuarters, A, 1996)	0.84
" The AUC0-24 ratios were similar to those following oral and rectal dosing in other studies involving cancer patients."	( Rectal controlled-release morphine: plasma levels of morphine and its metabolites following the rectal administration of MST Continus 100 mg. Campbell, WI, 1996)	0.59
" The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise."	( Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats. Bollengier, F; Engelborghs, S; Finné, E; Matton, A; Vanhaeist, L, 1996)	0.52
" The dose-response curve for M6G was shifted to the right by prior administration of M3G."	( Lack of morphine-6-glucuronide antinociception after morphine treatment. Is morphine-3-glucuronide involved? Cabanes, CG; Faura, CC; Horga, JF; Olaso, JM, 1996)	0.73
"IVPCA ketamine in combination with morphine provides superior postsurgical pain relief at lower dosage and with fewer side effects than morphine alone."	( Comparison of morphine and morphine with ketamine for postoperative analgesia. Colclough, GW; Javery, KB; Steger, HG; Ussery, TW, 1996)	0.93
" Treatment included naloxone (12 patients), admission to the pediatric intensive care unit (8), ventilation (5), and reduction in dosage (1)."	( Opiate-induced respiratory depression in pediatric patients. Choonara, IA; Cousins, A; Gill, AM; Nunn, AJ, 1996)	0.29
" The lateral hypothalamus met these five measures: (i) 81% of the lateral hypothalamus neurons (247/304) responded to noxious stimuli using a single cell recording procedure; (ii) stimulation of the periaqueductal gray-dorsal raphe area or the habenula modulated 98% and 87% of the lateral hypothalamus noxious-evoked activity; (iii) microiontophoretically applied morphine modulated 77% of the lateral hypothalamus noxious evoked activity; (iv) electrical stimulation of the lateral hypothalamus produced behavioral analgesia proportional to the stimulus intensity as assessed by the tail flick assay; and (v) morphine application into the lateral hypothalamus produced behavioral analgesia in a dose-response manner using the tail flick assay."	( Lateral hypothalamus: site involved in pain modulation. Dafny, N; Dong, WQ; Prieto-Gomez, C; Qiao, JT; Reyes-Vazquez, C; Stanford, J, 1996)	0.46
" There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose."	( Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy. Dews, TE; Ebrahim, Z; Fried, A; Oswalt, K; Paranandi, L; Schubert, A, 1996)	0.91
"The analgesic and sedative effects of intravenous morphine or pethidine and their effect on anxiety were compared in a prospective, double-blind, randomised dose-response study."	( Lack of analgesic effect of systemically administered morphine or pethidine on labour pain. Ekblom, A; Ekman-Ordeberg, G; Hjelm, A; Irestedt, L; Olofsson, C, 1996)	0.8
" However, dose-response studies indicate that the induction of morphine tolerance following 3 days of chronic morphine administration was blocked in antisense but not mismatch ODN or saline-treated mice."	( An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice. Inturrisi, CE; Kest, B; Lee, CE; McLemore, GL, 1996)	0.76
" DBA/2 but not C57BL/6 acquired self-administration of morphine with a bell-shaped unit dose-response curve."	( Enhancement of morphine self-administration in drug naive, inbred strains of mice by acute emotional stress. Kuzmin, A; Semenova, S; Van Ree, JM; Zvartau, EE, 1996)	0.89
" For this debate, controlled clinical studies on the opioid-sparing effect of different analgesic techniques are mentioned, and preferably studies with multiple dosing of analgesics and/or a reasonably large patient sample size."	( Postoperative opioid analgesia: time for a reconsideration? Callesen, T; Kehlet, H; Rung, GW, 1996)	0.29
" We measured the tail flick latency in response to thermal stimulation of the tail on a hot plate (53 degrees C), and determined dose-response functions of IT, EP and IV morphine, L-NAME, and morphine co-administered with subeffective doses of L-NAME."	( Antinociceptive synergistic interaction between morphine and n omega-nitro 1-arginine methyl ester on thermal nociceptive tests in the rats. Naito, H; Yamaguchi, H, 1996)	0.74
" In addition, a dose-response relationship was suggested."	( Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship. Angelilli, ML; Baker, D; Covington, C; Delaney-Black, V; Hack, C; Long, J; Nordstrom-Klee, B; Ostrea, E; Romero, A; Silvestre, MA; Tagle, MT, 1996)	0.29
" A dose-response relationship was evident."	( Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship. Angelilli, ML; Baker, D; Covington, C; Delaney-Black, V; Hack, C; Long, J; Nordstrom-Klee, B; Ostrea, E; Romero, A; Silvestre, MA; Tagle, MT, 1996)	0.29
" This retrospective, descriptive study identifies the demographic characteristics, dosing patterns, and side-effects evident in vascular patients placed on IV morphine PCA following surgery."	( Acute pain management: evaluation of the effectiveness of intravenous patient-controlled analgesia with vascular patients. Maxwell, LE, 1996)	0.49
" The dosage of epidural morphine used in this study was a likely explanation of this depression."	( Does morphine premedication influence the pain and consumption of postoperative analgesics after total knee arthroplasty? Hendolin, H; Kokki, H; Nuutinen, L; Tuomisto, L, 1996)	1.11
" Repetitive dosing (1/4 of the greatest dose every 30 min) was as effective as a single bolus dose for both drugs."	( Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention. Gebhart, GF; Stitt, S; Traub, RJ, 1995)	0.53
" At various times during and after the dosing protocol, approximately 50 mg of hair was shaved from a different area of the animals' backs and analyzed for codeine and morphine concentrations by ion-trap gas chromatography-mass spectrometry."	( Distribution of codeine and morphine into rat hair after long-term daily dosing with codeine. Gygi, SP; Rollins, DE; Wilkins, DG, 1995)	0.78
" We also examined tolerance on these analgesic systems by using a daily morphine injection paradigm which shifts the dose-response curve for systemic morphine approximately 2-fold after 5 days."	( Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance. Jain, S; Kolesnikov, YA; Pasternak, GW; Wilson, R, 1996)	0.92
" The mean settings for morphine dosage were a loading dose of 114."	( Patient-controlled analgesia after spinal fusion for idiopathic scoliosis. Beaulieu, P; Cyrenne, L; Mathews, S; Villeneuve, E; Vischoff, D, 1996)	0.6
" After preconstriction with the selective alpha 1-adrenergic receptor agonist phenylephrine, dose-response curves were constructed to (1) opiate receptor agonists morphine (1 to 30 micrograms/min) or fentanyl (0."	( Morphine-induced venodilation in humans. Abiose, A; Blaschke, TF; Grossmann, M; Hoffman, BB; Tangphao, O, 1996)	1.93
" This effect appeared to be dose-dependent, with patients in the lornoxicam 4 mg or morphine 10 mg groups recording significantly lower TOTPAR0-4 scores than patients in the higher dosage groups of these drugs."	( Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine. Bang, U; Ersbøll, AK; Hansen, HJ; Ingerslev, J; Larsen, U; Nielsen, O; Nørholt, SE; Sindet-Pedersen, S, 1996)	0.74
" This was done to evaluate the dose-response effect of these drugs when used for postoperative pain relief, and the results were applied to phase II of the study, in which all patients received ketamine pretreatment (total 30 mg) with each dose of lidocaine administered before and during surgery."	( Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control. Ho, ST; Liaw, WJ; Su, YF; Tung, CS; Wong, CS, )	0.4
" The resulting lowered dosage of epidural morphine needed for postoperative pain relief reduces, in turn, the incidence of side effects."	( Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control. Ho, ST; Liaw, WJ; Su, YF; Tung, CS; Wong, CS, )	0.66
" The high dosage of morphine required to induce anticarcinogenic effects is also discussed."	( Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mRNA expression. Fujiki, H; Okabe, S; Sueoka, E; Sueoka, N, 1996)	0.93
"Tolerance was produced in mice given morphine subcutaneously and was assessed by a cumulative dose-response analysis using the tail-flick test."	( Ketamine attenuates and reverses morphine tolerance in rodents. Elliott, KJ; Inturrisi, CE; Shimoyama, M; Shimoyama, N, 1996)	0.85
" Dose-response curves were obtained for each drug individually; for morphine:clonidine at 1:3, 1:1, and 1:0."	( Interaction of morphine and clonidine on gastrointestinal transit in mice. Pol, O; Puig, MM; Warner, W, 1996)	0.88
" We conclude that subarachnoid morphine at the dosage used produces no apparent benefit in sheep which have had stifle surgery, and in fact may cause detrimental side effects, such as hindlimb weakness, and pruritus or irritation of the hindquarters."	( Experiences with morphine injected into the subarachnoid space in sheep. Dunlop, CI; Turner, AS; Wagner, AE, )	0.76
" Buprenorphine, when injected systemically, revealed a potent analgesic effect by tailflick assay, with a biphasic dose-response curve, which was reversed by naloxone."	( Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa 3 analgesia. Peter, Y; Pick, CG; Schreiber, S; Weizman, R, 1997)	0.3
" No dose-response relationships could be elicited with U-50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO-treated animals."	( Peripheral effects of opioids in a model of intestinal inflammation in mice. Pol, O; Puig, MM; Sanchez, B, 1996)	0.29
"In a double-blind randomised study, two dosing regimens for controlled-release morphine tablets were compared against placebo to ascertain the extent of prophylactic postoperative pain control in 51 women undergoing abdominal hysterectomy."	( Pretreatment with controlled-release morphine for pain after hysterectomy. Cruickshank, RH; Ellis, FR; Spencer, A, 1996)	0.79
" Five patients showed symptoms of compression of the cauda equina or spinal cord shortly after the start of combined IT administration of morphine and bupivacaine in a dosage usually not associated with neurologic symptoms."	( Neurological impairment during long-term intrathecal infusion of bupivacaine in cancer patients: a sign of spinal cord compression. Crul, BJ; van Dongen, RT; van Ee, R, 1997)	0.5
" However, the time-course of potency changes in morphine analgesia as determined in dose-response studies and biochemical correlates of PTX treatment have not been reported to date."	( Time-dependent effects of in vivo pertussis toxin on morphine analgesia and G-proteins in mice. Breivogel, C; Childers, S; Munirathinam, G; Selly, D; Shah, S; Yoburn, BC, 1997)	0.8
" At 7 weeks of age, dose-response curves were obtained with morphine (10, 31."	( Influence of chronic prenatal and postnatal administration of naltrexone in locomotor activity induced by morphine in mice. Luján Estrada, M; Medina Jiménez, M; Rodríguez, R, 1997)	0.75
" The result strongly suggests a synergy from this combination that warrants a formal study of the dose-response relationship involved in this treatment and the mechanism by which this effect is achieved."	( Epidural coadministration of ketamine, morphine and bupivacaine attenuates post-herpetic neuralgia--a case report. Cherng, CH; Ho, ST; Liaw, WJ; Shen, TT; Wong, CS, 1996)	0.56
" Self-administration of cocaine (by rats) and morphine (by mice) was readily initiated and showed an inverted U-shaped unit dose-response curve."	( Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice. Gerrits, MA; Kuzmin, AV; Semenova, S; Van Ree, JM; Zvartau, EE, 1997)	0.8
" The pharmacokinetic profile of Kapanol exhibited a significantly higher Cmin (minimum plasma morphine concentration), less fluctuation in plasma morphine concentration throughout the dosing interval, a longer Tmax (time associated with the maximum morphine concentration) and a greater time that the plasma morphine concentration was > or = 75% of Cmax (an index of the control the formulation exerts over the morphine release rate) compared to that of MS Contin."	( Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain. Cherry, DA; Conn, DA; Gourlay, GK; Hood, GM; Onley, MM; Plummer, JL; Tordoff, SG, 1997)	0.52
" We now report a prospective randomized study evaluating the effectiveness and dosage of various concentrations of intravesical morphine infusions."	( Intravesical morphine analgesia after bladder surgery. Cangiano, T; Cohen, D; Cubina, M; Duckett, JW; Howe, C, 1997)	0.87
" injections of morphine or fentanyl, produced antinociceptive tolerance as shown by a significant rightward displacement of the agonist dose-response curves compared to controls."	( Competitive and non-competitive NMDA antagonists block the development of antinociceptive tolerance to morphine, but not to selective mu or delta opioid agonists in mice. Bilsky, EJ; Hruby, VJ; Inturrisi, CE; Porreca, F; Sadée, W, 1996)	0.86
" Area under the concentration-time curve and maximum serum concentrations were significantly greater for the section of the curve following dosing at 7:30 h than following dosing at 19:30 h in the 12-h treatment group."	( Steady-state pharmacokinetics of oral sustained-release morphine sulphate in dogs. Dohoo, S, 1997)	0.54
" The dose-response curve was shifted dose dependently to the right by the muscarinic antagonist scopolamine but not by the opioid antagonist naltrexone."	( Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic. Bymaster, FP; Calligaro, DO; Delapp, NW; Hansen, KT; Mitch, CH; Olesen, PH; Sauerberg, P; Shannon, HE; Sheardown, MJ; Suzdak, PD; Swedberg, MD; Ward, JS, 1997)	0.3
" Tolerance was assessed as shifts in morphine dose-response curves on the tail-flick test."	( Associative and nonassociative tolerance: the effects of dose and interdose interval. Cox, LS; Tiffany, ST, )	0.4
" The sweat patch was applied 10 min before the first dosage and removed approximately 24 h later, minutes before the next dosage."	( Sweat testing for heroin and metabolites in a heroin maintenance program. Brenneisen, R; Bundeli, P; Kintz, P; Mangin, P, 1997)	0.3
"5 mg of morphine with a 6-minute lockout and a 4-hour maximum dosage of 30 mg."	( Postoperative analgesia with parenteral opioids: does continuous delivery utilizing a transdermal opioid preparation affect analgesic efficacy or patient safety? Paige, D; Sevarino, FB; Silverman, DG; Sinatra, RS, 1997)	0.73
"The time and dosage of morphine administered was recorded."	( Postoperative analgesia with parenteral opioids: does continuous delivery utilizing a transdermal opioid preparation affect analgesic efficacy or patient safety? Paige, D; Sevarino, FB; Silverman, DG; Sinatra, RS, 1997)	0.61
"5 g/kg) inhibited naltrexone-induced stimulation of testosterone secretion and shifted the naltrexone dose-response curve to the right."	( Interactions between alcohol- and opioid-induced suppression of rat testicular steroidogenesis in vivo. Adams, ML; Cicero, TJ; Meyer, ER, 1997)	0.3
" Accordingly dosage should be reduced or other opioids be considered in such cases."	( [Morphine metabolism--pharmacokinetics and pharmacodynamics]. Andersen, G; Christrup, LL; Sjøgren, P, 1997)	1.21
" The present study provides systematic dose-response analyses indicating that NTX elicited optimal enhancement of morphine's antinociceptive potency in mice when co-administered (i."	( Ultra-low doses of naltrexone or etorphine increase morphine's antinociceptive potency and attenuate tolerance/dependence in mice. Crain, SM; Shen, KF, 1997)	0.76
" There was no dose-response evident."	( Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Carroll, D; Kalso, E; McQuay, HJ; Moore, RA; Tramèr, MR, 1997)	0.58
" Conversely, an antisense probe selectively targeting nNOS-2 blocks morphine analgesia, shifting the morphine dose-response curve over 2-fold to the right."	( Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: evidence for opposing NO actions on morphine analgesia and tolerance. Babey, AM; Jain, S; Kolesnikov, YA; Pan, YX; Pasternak, GW; Wilson, R, 1997)	0.74
" These systems allowed bolus dosing and also provided a basic level of analgesic protection through continuous drug infusion."	( Differences among patients in opioid self-administration during bone marrow transplantation. Chapman, CR; Donaldson, GW; Hautman, B; Jacobson, RC, 1997)	0.3
" Under this simple schedule, dose-response curves were determined for diazepam, morphine, pentobarbital, and phencyclidine."	( Behavior of rats under fixed consecutive number schedules: effects of drugs of abuse. Hardin, JL; McMillan, DE; Snodgrass, SH, 1997)	0.52
" In dose-response studies, 3-methoxynaltrexone (2."	( 3-Methoxynaltrexone, a selective heroin/morphine-6beta-glucuronide antagonist. Brown, GP; Chang, A; King, MA; Leventhal, L; Pasternak, GW; Rossi, GC; Yang, K, 1997)	0.56
" Using multiple logistic regression, three factors are identified as significantly impedimental to staying at home: high morphine dosage (> 60 mg daily oral morphine equivalence), direct transfer from hospital to hospice, and living on the second or upper floors in an apartment building."	( [Determinants associated with location of terminal care in the cancer patient]. Adachi, M; Kon, H, 1997)	0.5
" Overall, these data indicate that the starting dose and increment dose can impact on morphine's potency determined by cumulative dosing protocols."	( The effect of cumulative dosing on the analgesic potency of morphine in mice. Duttaroy, A; Farrell, F; Kirtman, R; Monderson, T; Philippe, J; Phillips, M; Yoburn, BC, 1997)	0.76
"7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids."	( Dose ratio between morphine and hydromorphone in patients with cancer pain: a retrospective study. Bruera, E; Hanson, J; Lawlor, P; Turner, K, 1997)	0.63
" The dose-response curves were first obtained for each drug alone."	( Isobolographic analysis of interactions between intravenous morphine, propacetamol, and diclofenac in carrageenin-injected rats. Benoist, JM; Fletcher, D; Gautron, M; Guilbaud, G, 1997)	0.54
"We previously reported that stimulus properties of morphine can be assessed in a passive avoidance conditioning paradigm using a single dosing discrimination test."	( Footshock facilitates discrimination of stimulus properties of morphine. Borlongan, CV; Watanabe, S, 1997)	0.79
"6-fold rightward shift in the morphine dose-response curve."	( Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance. Fairbanks, CA; Wilcox, GL, 1997)	0.85
" It also did not appear that the sustained release formulation provided sufficiently prolonged release of morphine sulfate from the tablet matrix in dogs to allow prolonged dosing intervals compared to NSRMS."	( Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations. Dohoo, SE; Tasker, RA, 1997)	0.81
" This dosing regimen can be prepared with 400 microg naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg."	( Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Fortney, J; Gan, TJ; Ginsberg, B; Glass, PS; Jhaveri, R; Perno, R, 1997)	0.52
" In the test of physical dependence-producing potential with the drug-admixed food method in rats, vigabatrin and diazepam were given to rats mixed with food for 28 days in an increasing dosage schedule, followed by feeding a drug-free diet to observe withdrawal signs for 7 days."	( Drug dependence study on vigabatrin in rhesus monkeys and rats. Takada, K; Yanagita, T, 1997)	0.3
" Larger studies are needed to establish which patients are most likely to benefit and optimal dosage regimens."	( Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer. Boyd, KJ; Kelly, M, 1997)	0.81
" They were found fairly potent in rat tail flick and mouse phenylquinone writhing assays but the dose-response curves were rather shallow as compared to that of morphine."	( Apparent antinociceptive and anti-inflammatory effects of GYKI 52466. Kedves, R; Máté, I; Székely, JI; Tarnawa, I; Török, K, 1997)	0.49
"0 mg/kg clocinnamox displaced the morphine dose-response curve 4-fold to the right of the control curve and 10 mg/kg clocinnamox eliminated morphine's antinociceptive effects at doses up to 1000 mg/kg for at least seven days."	( Clocinnamox dose-dependently antagonizes morphine-analgesia and [3H]DAMGO binding in rats. Paronis, CA; Woods, JH, 1997)	0.84
" Administration of morphine, DPDPE, or U50,488H three times daily for 3 days according to an escalating dosing schedule resulted in analgesic tolerance as indicated by an increase in analgesic ED50 values using the tail-flick test in mice."	( The competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist LY293558 attenuates and reverses analgesic tolerance to morphine but not to delta or kappa opioids. Inturrisi, CE; Kao, B; Kest, B; McLemore, G, 1997)	0.83
" doses of morphine, as demonstrated by a 120-fold rightward shift of the morphine dose-response curve."	( The nitric oxide/cyclic GMP system at the supraspinal site is involved in the development of acute morphine antinociceptive tolerance. Bidlack, JM; Hill, KP; Xu, JY, 1998)	0.92
" As a conclusion, no analgesic effect of alpha-trinositol at the dosage used was observed in the postoperative patients studied."	( Postoperative recovery after cholecystectomy by minilaparotomy: a randomized double-blind comparison between alpha-trinositol and placebo. Holmin, T; Landquist, E; Luttropp, HH; Westerling, D, 1997)	0.3
" Similarly, the progressive and complete loss of analgesia in CD-1 mice seen with repeated dosing of the delta ligand [D-Pen2, D-Pen5]enkephalin is not observed in 129/SvEv mice."	( Lack of morphine and enkephalin tolerance in 129/SvEv mice: evidence for a NMDA receptor defect. Jain, S; Kolesnikov, Y; Pasternak, GW; Wilson, R, 1998)	0.73
" It shifted the dose-response curve of morphine to the left."	( The interaction of FK409, a novel nitric oxide releaser, and peripherally administered morphine during experimental inflammation. Nozaki-Taguchi, N; Yamamoto, T, 1998)	0.79
") After initiating morphine or making any change of dose or route of administration, the dosage should be evaluated after approximately 24 hours."	( The management of chronic pain in patients with breast cancer. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Canadian Society of Palliative Care Physicians. Canadian Association of Radiation Oncologist , 1998)	0.63
" Sixteen patients were administered dextropropoxyphene (DPP) in a dosage ranging from 120 mg to 240 mg daily (group 1), and 16 patients were administered the lowest doses (20 mg daily) of commercially available controlled-release morphine (group 2)."	( Dextropropoxyphene versus morphine in opioid-naive cancer patients with pain. Agnello, A; Dardanoni, G; Garofalo, S; Mercadante, S; Salvaggio, L, 1998)	0.78
" This rightward shift of the morphine dose-response curve was reversed by the intrathecal administration of either the CCKA receptor antagonist, lorglumide, or the CCKB receptor antagonist, PD135, 158."	( Pentobarbital antagonism of morphine analgesia mediated by spinal cholecystokinin. Fujimoto, JM; Lin, W; Rady, JJ, 1998)	0.89
" For these changes in the kinetic profile of morphine (as MST) in cirrhotic patients, who experienced more sedation than controls, a smaller dose study together with longer dosing intervals is recommended."	( Pharmacokinetics of controlled release morphine (MST) in patients with liver cirrhosis. el-Kabsh, MY; Emara, SE; Fouad, EA; Kotb, HI, 1997)	0.83
" CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22."	( GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia. Asadi, I; Fernández, A; Serrano, JS; Serrano, MI; Serrano-Martino, MC, 1998)	0.3
" MXL capsules were shown to provide effective analgesia over the 24-h dosing interval which was comparable to that of MST Continus tablets administered twice daily."	( A randomized crossover study comparing the efficacy and tolerability of a novel once-daily morphine preparation (MXL capsules) with MST Continus tablets in cancer patients with severe pain. McDonald, CJ; Miller, AJ; Mortimer, PG; O'Brien, T, 1997)	0.52
" If the instillation occurs at the lumbosacral level (between the last lumbar and the first sacral vertebra), a dosage of 70 mg morphine/day cannot induce the same pain relief as 450 mg subcutaneous morphine (VAS score 5/10 vs."	( Subcutaneous morphine is superior to intrathecal morphine for pain control in a patient with hypernephroma. Devulder, JE, 1998)	0.87
" In dose-response tests, subjects rarely responded on the U-50,488H-appropriate key when morphine was administered or on the morphine-appropriate key when they received U-50,488H."	( Establishing morphine and U-50,488H as discriminative stimuli in a three-choice assay with pigeons. Makhay, MM; Poling, A; Young, AM, 1998)	0.89
" was initiated and the dosage was titrated upward to a total of 6613 mg/d by hospital day 16."	( Continuous fentanyl infusion: use in severe cancer pain. Dunlap, DS; Lenz, KL, 1998)	0.3
" Dose-response curves for 1DMe in the presence of naltrindole or naltrexone, delta- and mu-opioid selective antagonists respectively, indicate that 1DMe preferentially reversed mu-receptor-mediated but increased delta-receptor-mediated analgesia."	( Differential modulation of mu- and delta-opioid antinociception by neuropeptide FF receptors in young mice. Desprat, C; Zajac, JM, 1997)	0.3
" Compared with immediate-release (IR) morphine, this formulation provides the benefit of dosing every 12 hours."	( Controlled-release morphine tablets in patients with chronic cancer pain: a narrative review of controlled clinical trials. Warfield, CA, 1998)	0.9
"Twice-daily dosing of CR morphine provides convenient, safe, and effective relief of cancer pain."	( Controlled-release morphine tablets in patients with chronic cancer pain: a narrative review of controlled clinical trials. Warfield, CA, 1998)	0.93
"Case 1: A 72-year-old 84-kg white man with cancer of the bladder and bone metastases had intense back and leg pain that was treated with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice daily."	( Respiratory depression following administration of intrathecal bupivacaine to an opioid-dependent patient. Barjhoux, CE; Danel, VC; Lemoigne, AH; Mallaret, MP; Piquet, CY; Vincent, FH, 1998)	0.5
"5 nmol/h) of the agonist for 5 days, the OFQ dose-response curves for its antinociceptive effect in the tail-flick and paw-pressure tests were significantly shifted to the right."	( Antinociceptive and morphine modulatory actions of spinal orphanin FQ. Henderson, G; Jhamandas, KH; Sutak, M, 1998)	0.62
"0001) in the nociceptive threshold of the cows with cumulative dosing of morphine sulphate was noticed."	( A thermal threshold assay to measure the nociceptive response to morphine sulphate in cattle. Ewing, KK; Hurnik, JF; Machado Filho, LC, 1998)	0.77
" After the block, her conditions improved markedly at a dosage of 300 mg."	( [Long-term administration of large doses of oral morphine for chronic pain]. Kitajima, T; Okuda, Y; Saito, K; Takanishi, T, 1998)	0.55
"The availability of various dosage forms allows morphine to be administered in a number of ways."	( Intravaginal morphine: an alternative route of administration. Lamb, J; Ostrop, NJ; Reid, G, )	0.76
" Morphine sulfate was administered using a cumulative dosing procedure (2."	( Chronic running-wheel activity decreases sensitivity to morphine-induced analgesia in male and female rats. D'Anci, KE; Gerstein, AV; Kanarek, RB; Mathes, WF; Wildman, RP, 1998)	1.46
"The concurrent administration of spinal morphine and systemic buprenorphine produces an antinociceptive effect that is greater than what could have been predicted from individual dose-response curves."	( Antinociceptive effect induced by the combined administration of spinal morphine and systemic buprenorphine. Jurna, I; Metzner, J; Nemirovsky, A; Niv, D; Rudick, V; Urca, G, 1998)	0.8
" Morphine dose-response curves were carried out for morphine and fixed doses of ACEA 1021 (12 microg) or AP-5 (10 microg)."	( Effects of intrathecal NMDA and non-NMDA antagonists on acute thermal nociception and their interaction with morphine. Nishiyama, T; Weber, E; Yaksh, TL, 1998)	1.42
"There are a number of modified release formulations of morphine with recommended dosage intervals of either 12 or 24 hours, including tablets (MS Contin, Oramorph SR), capsules (Kapanol, Skenan), suspension and suppositories."	( Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine. Gourlay, GK, 1998)	0.78
" infusion of morphine (half dosage of daily oral dosage), or subcutaneous injection (one sixth dosage of daily oral morphine) while preoperative epidural morphine was continued throughout the perioperative period."	( [Perioperative managements of the patients with cancer-pain receiving morphine]. Maeda, S; Matsuda, M; Murakawa, K; Noma, K; Tashiro, C; Uemura, Y, 1998)	0.9
" The purpose of this study was to describe patient responses to continuous intrathecal morphine over the course of one year with respect to morphine dosage used, complications and subjective assessments of pain."	( Managing chronic nonmalignant pain with continuous intrathecal morphine. Pillay, KV; Valentino, L; Walker, J, 1998)	0.76
" Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation."	( Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Agnello, A; Barresi, L; Calderone, L; Casuccio, A; Mercadante, S; Serretta, R, 1998)	1.95
" Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient."	( Differential effects of fentanyl and morphine on intracellular Ca2+ transients and contraction in rat ventricular myocytes. Damron, DS; Kanaya, N; Murray, PA; Zakhary, DR, 1998)	0.93
" Morphine dosage was increased to maximally 3 x 30 mg daily, depending on effectiveness and side effects, dyspnoea at rest and immediately after a 6-min walk (assessed with Borg's visual analog scale), maximal walking capacity were determined, as well as blood gases, respiratory minute volume and the respiratory drive (airway occlusion pressure [P0."	( [Value of orally administered retard morphine for therapy of severe pulmonary emphysema of the pink-puffer type. A pilot study]. Köhler, D; Schönhofer, B, 1998)	1.48
" Groups of six rats received either vehicle or analgesic drug and antinociception was evaluated by evaluating the dose-response curves over time."	( Antinociceptive effects of S(+)-ketoprofen and other analgesic drugs in a rat model of pain induced by uric acid. Cabré, F; Díaz, I; Fernández-Guasti, A; López-Muñoz, FJ; Mauleón, D; Tost, D; Ventura, R, 1998)	0.3
" The maximum dosage of morphine in the period of home therapy was 57."	( [Continuous injection therapy of morphine solution for terminally-ill patients at home]. Abe, K; Komatsu, H; Matsumoto, S; Terashima, H, 1998)	0.89
" Medical treatment at home consisted of dosage of morphine for 30 patients, parenteral nutrition for 30 patients, dosage of steroids for 29 patients, infusion of haloperidol for 8 patients, continuous draining of ascites for 6 patients, and continuous draining of intestinal fluid through nasogastric tube for 3 patients."	( [Home care for terminally ill cancer patients in 1997]. Ashino, Y; Kanno, A; Muto, A; Sato, M, 1998)	0.55
" A rightward shift of the dose-response curve was observed in rats made tolerant to systemic morphine with subcutaneous morphine pellets."	( Characterization of the antihyperalgesic action of a novel peripheral mu-opioid receptor agonist--loperamide. Nozaki-Taguchi, N; Yaksh, TL, 1999)	0.52
" After the tail-flick latencies returned to baseline levels, dose-response curves were generated to Mor, Clon, and Mor-Clon combinations in tolerant and control mice."	( Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. Fairbanks, CA; Wilcox, GL, 1999)	0.57
" Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753."	( Effects of kappa opioids in the inflamed rat colon. Gebhart, GF; Sengupta, JN; Snider, A; Su, X, 1999)	0.3
" Finally, shifts in the morphine dose-response lines after 24-h pretreatment with the four dihydrocodeinone compounds suggest that the nitrocinnamoylamino derivatives may produce a greater magnitude long-term antagonism of morphine-induced antinociception than the chlorocinnamoylamino analogs."	( Nitrocinnamoyl and chlorocinnamoyl derivatives of dihydrocodeinone: in vivo and in vitro characterization of mu-selective agonist and antagonist activity. Archer, S; Bidlack, JM; Hill, KP; Jiang, Q; McLaughlin, JP; Sebastian, A, 1999)	0.61
" The concentrations of the drug in the tissues sampled were determined to be similar to those normally encountered in human overdoses and were correlated with the dosage of morphine that had been administered."	( Determination of drug levels in larvae of Lucilia sericata (Diptera: Calliphoridae) reared on rabbit carcasses containing morphine. Bécart, A; Bourel, B; Deveaux, M; Gosset, D; Hédouin, V; Martin-Bouyer, L; Tournel, G, 1999)	0.7
" Dose-response relationships show that higher doses of ibuprofen may be particularly effective."	( Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. McQuay, HJ; Moore, RA, 1998)	0.3
"Under steady-state conditions in the first dosing interval, mean maximum plasma concentrations for morphine were 19."	( Bioequivalence study of two morphine extended release formulations after multiple dosing in healthy volunteers. Blume, HH; Crawford, F; Elze, M; Evers, G; Heinrich-Nols, J; Larsimont, V; Lee, LS; Schug, BS, 1999)	0.81
" Morphine analgesia was inhibited by dynorphin as shown by a rightward shift of the morphine dose-response curve."	( Antianalgesic action of dynorphin A mediated by spinal cholecystokinin. Fujimoto, JM; Holmes, BB; Rady, JJ, 1999)	1.21
" This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia."	( Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. Chehade, J; Duffy, L; Gajraj, N; Johnson, ER; Joshi, GP; Wesevich, J, 1999)	0.77
" Simulation of effect-site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine."	( Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Ahne, G; Geisslinger, G; Kobal, G; Lötsch, J; Weiss, M, 1999)	0.76
" The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine."	( Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Ahne, G; Geisslinger, G; Kobal, G; Lötsch, J; Weiss, M, 1999)	0.85
" The dose-response curves for oxymorphone and hydromorphone were shifted 5- and 12."	( Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. Cichewicz, DL; Martin, ZL; Smith, FL; Welch, SP, 1999)	0.3
" In contrast, there were no sex differences in morphine's hotplate or tail withdrawal effects under repeated (1-week interval) dosing conditions."	( Sex differences in development of morphine tolerance and dependence in the rat. Bartok, RE; Craft, RM; King, SJ; Stratmann, JA; Walpole, TI, 1999)	0.84
" Orderly dose-response functions suggested that our cumulative-dosing procedure is an efficient way of determining dose-response functions for multiple opioids within the same subjects within the same study."	( Subjective, psychomotor, and physiological effects of cumulative doses of opioid mu agonists in healthy volunteers. Walker, DJ; Zacny, JP, 1999)	0.3
" The average dose of morphine administered during each of the 8-hour dosing intervals was approximately 12 mg."	( Prescribing of analgesics in trauma patients. Chopda, S; Erstad, BL; Esser, MJ, 1997)	0.62
" The availability of a ready to use parental dosage form of morphine and bupivacaine is comfortable for health care workers."	( Long-term stability of morphine and bupivacaine mixture for spinal use. Beelen, M; Burger, DM; Essink-Tjebbes, CM; Hekster, YA; Wuis, EW, 1999)	0.86
" This patient's clinical course indicates that oral oxycodone can be used safely and to good effect at high dose, that the milligram relative potency ratio for oral oxycodone to parenteral morphine during repeated dosing is 3:1, and suggests that availability of multiple formulations of oxycodone may benefit cancer patients."	( The relative potency between high dose oral oxycodone and intravenous morphine: a case illustration. Doona, M; Walsh, D; Zhukovsky, DS, 1999)	0.73
"There was evidence of context-specific tolerance across both testing methods, with a rightward shift of dose-response curves of paired relative to unpaired animals."	( Context-specific morphine tolerance on the paw-pressure and tail-shock vocalization tests: evidence of associative tolerance without conditioned compensatory responding. Cepeda-Benito, A; Cox, LS; Tiffany, ST, 1999)	0.64
" Morphine dosage was negatively associated with age (r = -0."	( High dose morphine use in the hospice setting. A database survey of patient characteristics and effect on life expectancy. Adunsky, A; Bercovitch, M; Waller, A, 1999)	1.62
"A fairly strong correlation exists between morphine dosage and some clinicodemographic data."	( High dose morphine use in the hospice setting. A database survey of patient characteristics and effect on life expectancy. Adunsky, A; Bercovitch, M; Waller, A, 1999)	0.97
" Morphine dosage must therefore be carefully controlled in patients with renal failure."	( [Morphine poisoning in chronic kidney failure. Morphine-6-glucuronide as a pharmacologically active morphine metabolite]. Caduff, B; Dubs, A; Wiedemeier, P, 1999)	2.12
" Glibenclamide enhanced spontaneous alternation performance in an inverted-U dose-response manner."	( ATP-sensitive potassium channel blockade enhances spontaneous alternation performance in the rat: a potential mechanism for glucose-mediated memory enhancement. Gold, PE; Nicholson, GM; Stefani, MR, 1999)	0.3
"To search for the optimal dosage of nalbuphine relief of intrathecal-morphine induced pruritus after caesarean section."	( Optimal dose of nalbuphine for treatment of intrathecal-morphine induced pruritus after caesarean section. Ketchada, U; Oranuch, K; Siriprapa, S; Somrat, C; Thipawan, R, 1999)	0.78
" Clinical applications are rare because of the lack of dose-response relationships in the studies performed to date, and questions remain regarding the mechanisms of drug incorporation into hair."	( Codeine concentration in hair after oral administration is dependent on melanin content. Ahlner, J; Förstberg-Peterson, S; Kågedal, B; Kronstrand, R; Larson, G, 1999)	0.3
" Assessments were made at 30 min, 60 min, then hourly after dosing for 12 h or until remedication."	( Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model. Brown, J; Clark, P; Curtis, GB; Johnson, GH; Lacouture, PG; O'Callaghan, R; Shi, M; Taylor, R, 1999)	0.54
" for generation of dose-response curves in the tail-flick test."	( Involvement of phospholipid signal transduction pathways in morphine tolerance in mice. Dewey, WL; Lohmann, AB; Smith, FL, 1999)	0.55
" The titrated dosages (a bolus dosage and a maintenance dosage) chosen by the nurses for the patient with slightly elevated vital signs differed significantly from the titrated dosages chosen by the same group of nurses for another patient with vital signs at the lower end of the stable range (t=3."	( Vital signs and nurses' choices of titrated dosages of intravenous morphine for relieving pain following cardiac surgery. Chuk, PK, 1999)	0.54
" The equipotent morphine dosage requirements were also not statistically different."	( Patient-controlled analgesia in postoperative cardiac surgery. Brush, B; Tsang, J, 1999)	0.65
" In contrast, repeated dosage twice daily for 10 days and ascending from 10 to 50 mg/kg resulted in a sharply delineated morphine-induced c-fos synthesis in the dorsomedial and lateral striatum, lateral septum, medial mammillary nuclei, anterior thalamus and, in part masked by a high background due to injection stress, in the cingulate cortex."	( Long-lasting sensitization towards morphine in motoric and limbic areas as determined by c-fos expression in rat brain. Erdtmann-Vourliotis, M; Höllt, V; Linke, R; Mayer, P; Riechert, U, 1999)	0.79
" Next, a morphine dose-response curve (1."	( Sensitization to daily morphine injections in rats with unilateral lesions of the substantia nigra. Easterling, KW; Holtzman, SG; Kimmel, HL; Volpicelli, LA, 1999)	1.03
" Furthermore, morphine-induced analgesia in a hot-plate test showed a leftward shift in the morphine dose-response curve after naloxone treatment."	( Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking. Hyytiä, P; Ingman, K; Korpi, ER; Laitinen, JT; Soini, SL, 1999)	0.66
" Data derived from the hand set signals are used by an expert algorithm to repeatedly adapt the drug dosage of the bolus and of the background infusion according to both current pain intensity and the patient's response to previous dosage."	( Smart technology improves patient-controlled analgesia: a preliminary report. Cade, JF; Lee, B; Morley, PT; Packer, JS; Rudolph, H, 1999)	0.3
" 18-Methoxycoronaridine produced a downward shift in the entire morphine dose-response curve without any displacement to the left or right."	( Attenuation of the reinforcing efficacy of morphine by 18-methoxycoronaridine. Glick, SD; Maisonneuve, IM, 1999)	0.8
" Inclusion of a fixed dose of 3-O-methylnaltrexone significantly shifted the analgesic dose-response curves for 6-acetylmorphine and heroin without altering the morphine dose-response curves."	( Antagonism of heroin and morphine self-administration in rats by the morphine-6beta-glucuronide antagonist 3-O-methylnaltrexone. Izzo, E; King, M; Koob, GF; Pasternak, GW; Walker, JR, 1999)	0.81
" The combinations of moxonidine-morphine and moxonidine-deltorphin II resulted in significant leftward shifts in the dose-response curves compared to those of each agonist administered separately."	( Moxonidine, a selective imidazoline/alpha(2) adrenergic receptor agonist, synergizes with morphine and deltorphin II to inhibit substance P-induced behavior in mice. Fairbanks, CA; Kitto, KF; Posthumus, IJ; Stone, LS; Wilcox, GL, 2000)	0.81
" Diazoxide (2 microg/mouse) shifted morphine's dose-response curve 47-fold, while levcromakalim (0."	( ATP-gated K(+) channel openers enhance opioid antinociception: indirect evidence for the release of endogenous opioid peptides. Lohmann, AB; Welch, SP, 1999)	0.58
") daily morphine dosage at study entry was 135 (127) mg, and the daily morphine dose at study completion was 244 (240) mg."	( Long-term patterns of morphine dosage and pain intensity among cancer patients. Melzack, R; Sloan, P, 1999)	1.05
" The following conclusions were reached: 1) MSC should be explained individually and repeatedly, 2) exact informations on a patient's status should be collected using scales and charts, 3) nurse charts should record when MSC is initially administered and when the dosage is changed, and 4) the cases of poorly controlled patients should be studied and specialists consulted if necessary."	( [Roles of outpatient nurses in the care of cancer patients receiving MS Contin tablets]. Naito, A; Sekiya, Y, 1999)	0.3
" Disposition was examined either following intraperitoneal dosing as a single dose or continuous infusion."	( Disposition of morphine in tissues of the pregnant rat and foetus following single and continuous intraperitoneal administration to the mother. Boulton, DW; DeVane, CL; Laizure, SC; Miller, RL; Simpkins, JW, 1999)	0.66
" Our results showed that morphine served as a positive reinforcing agent in both male and female rats in a place conditioning paradigm, but that the dose-response curves displayed marked sex-related differences."	( Gender differences in the reinforcing properties of morphine. Cicero, TJ; Ennis, T; Meyer, ER; Ogden, J, 2000)	0.86
" Existing models often fail to predict route-dependent intestinal metabolism, namely, little metabolism occurs after systemic dosing but notable metabolism exists after oral dosing."	( A new physiologically based, segregated-flow model to explain route-dependent intestinal metabolism. Cong, D; Doherty, M; Pang, KS, 2000)	0.31
" Acutely, parenteral coadministration of chloramphenicol and morphine resulted in an approximately 75% increase in the mean area under the serum morphine concentration-time curve but for chronic dosing there was no significant change in this curve, indicating that factors other than morphine concentrations contribute significantly to antinociception."	( Systemic coadministration of chloramphenicol with intravenous but not intracerebroventricular morphine markedly increases morphine antinociception and delays development of antinociceptive tolerance in rats. Lau, M; Lim-Fraser, MY; Nielsen, CK; Smith, MT; Wright, AW, 2000)	0.77
" Daily dosing requirements were less in the elderly for intermittent intravenous lorazepam, haloperidol, and morphine but not for midazolam (p=0."	( Frequency, severity, and treatment of agitation in young versus elderly patients in the ICU. Berthiaume, D; Fraser, GL; Prato, BS; Riker, RR; Wilkins, ML, 2000)	0.52
"3, 1, 3, and 10 microg) were administered intrathecally to obtain the dose-response curves and the 50% effective dose (ED(50)) for each drug."	( An analysis of drug interaction between morphine and neostigmine in rats with nerve-ligation injury. Choi, Y; Han, SM; Hwang, JH; Hwang, KS; Lee, DM; Park, PH, 2000)	0.57
" The combination of ziconotide and morphine produced an additive inhibition of formalin-induced tonic flinch responses and a significant leftward shift of the morphine dose-response curve in the paw pressure test."	( Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats. Bowersox, SS; Gao, D; Pettus, M; Phillips, C; Wang, YX, 2000)	0.79
" Behaviourally, rats co-administered sub-antinociceptive doses of oxycodone and morphine were similar to control rats dosed with saline, whereas rats that received equi-potent doses of either opioid alone, were markedly sedated."	( Co-administration of sub-antinociceptive doses of oxycodone and morphine produces marked antinociceptive synergy with reduced CNS side-effects in rats. Ross, FB; Smith, MT; Wallis, SC, 2000)	0.77
" The concept of rescue dosing in safe analgesic titration and management of breakthrough/incident pain is a key concept."	( Pharmacological management of cancer pain. Walsh, D, 2000)	0.31
" To minimise the total daily opioid dosage and the potential risk of a neonatal withdrawal syndrome due to opioids, the route of administration was changed from oral to epidural."	( Treatment of severe low back pain with opioids during pregnancy in a patient with incomplete tetraplegia. Göhring, UJ; Grond, S; Radbruch, L; Sabatowski, R, 2000)	0.31
" The dose-response of intrathecal morphine (1-320 microg) for both scratching and antinociception in all subjects was established."	( An experimental itch model in monkeys: characterization of intrathecal morphine-induced scratching and antinociception. Ko, MC; Naughton, NN, 2000)	0.82
" Pretreatment with nalmefene (32 microg/kg subcutaneously) produced approximately 10-fold rightward shifts of intrathecal morphine dose-response curves for both behavioral effects."	( An experimental itch model in monkeys: characterization of intrathecal morphine-induced scratching and antinociception. Ko, MC; Naughton, NN, 2000)	0.75
"The purpose of this study was to describe the dose-response relationship of epidural morphine for postcesarean analgesia for quality of analgesia and relation to the side effects of pruritus, nausea, and vomiting."	( Postcesarean epidural morphine: a dose-response study. Alves, DM; Nogami, WM; Palmer, CM; Van Maren, G, 2000)	0.85
"9-fold rightward shift of the cumulative dose-response curves."	( Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice. Danysz, W; Kozela, E; Popik, P, 2000)	0.51
" Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects."	( Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery. Brolin, RE; Choi, YK; Chou, S; Etesham, S; Pollak, P; Wagner, BK, 2000)	0.31
"A dose-response curve for intravenous morphine and vomiting was investigated in children having day-stay tonsillectomy."	( The dose-effect relationship for morphine and vomiting after day-stay tonsillectomy in children. Anderson, BJ; Barber, C; Holford, NH; Ralph, CJ; Stewart, AW, 2000)	0.86
" Compared to vehicle pretreated controls, 18-MC increased the potency of morphine, shifting the dose-response curve to the left, in acute morphine treated rats; however, 18-MC did not alter the potency of morphine in rats treated repeatedly with morphine."	( The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment. Glick, SD; Maisonneuve, IM; Szumlinski, KK, 2000)	0.74
"To compare morphine dosage and effectiveness in AIDS patients with/without prior substance use and pain, a prospective, open-label case series lasting 3-18 days was conducted in both outpatients and inpatients at major pain service teaching programs."	( A titrated morphine analgesic regimen comparing substance users and non-users with AIDS-related pain. Kaplan, R; Ries, K; Slagle, S; Slywka, J, 2000)	1.09
" After obtaining dose-response curves for each agent, combinations of morphine and AP-5, ACEA 1021 or ACEA 2752 were tested for their effect on the number of flinches in the formalin test and for associated side-effects, such as motor disturbances, flaccidity, and agitation/allodynia."	( Interaction between intrathecal morphine and glutamate receptor antagonists in formalin test. Nishiyama, T, 2000)	0.82
" Nevertheless, prescription parameters such as the bolus dosage and the possible association of a continuous background infusion have not yet been standardized."	( [Patient-controlled analgesia for prolonged pain in the child. An open-label feasibility study of a standardized method]. Bockenmeyer, J; Duval, M; Escot, A; Faye, A; Legrand, F; Rohrlich, P; Vernois, S; Vilmer, E; Wood, C, 2000)	0.31
"Thirty-three children, aged four to 17, hospitalized in a pediatric hematology ward, benefited from PCA with a standardized prescription: a bolus dosage of at least 25 mg/kg, without a background infusion."	( [Patient-controlled analgesia for prolonged pain in the child. An open-label feasibility study of a standardized method]. Bockenmeyer, J; Duval, M; Escot, A; Faye, A; Legrand, F; Rohrlich, P; Vernois, S; Vilmer, E; Wood, C, 2000)	0.31
" Dose-response curves for morphine and clonidine alone and combined at a 1:1 potency ratio were obtained, and doses producing a 50% and 60% inhibition were calculated (ED50, ED60)."	( Intestinal inflammation and morphine tolerance alter the interaction between morphine and clonidine on gastrointestinal transit in mice. Pol, O; Puig, MM; Warner, W, 2000)	0.9
"In naive and tolerant mice, the combination induced linear dose-response curves up to the ED60 and then reached a plateau."	( Intestinal inflammation and morphine tolerance alter the interaction between morphine and clonidine on gastrointestinal transit in mice. Pol, O; Puig, MM; Warner, W, 2000)	0.6
" The dose that yielded 50% of the maximum possible effect (ED50) and dose-response and time-course curves were determined for the ketamines (30-300 microg), morphine (0."	( The effects of ketamine and its enantiomers on the morphine- or dexmedetomidine-induced antinociception after intrathecal administration in rats. Benedek, G; Dobos, I; Horvath, G; Joó, G; Kekesi, G; Klimscha, W; Szikszay, M, 2000)	0.76
" Chronic (daily) dosing with a dose that reduced, but did not eliminate, responding then occurred until response rates stabilized."	( Effects of cocaine and morphine under mixed-ratio schedules of food delivery: support for a behavioral momentum analysis. Byrne, T; Christian, L; Lesage, MG; Poling, A, 2000)	0.62
" In the first study, U50,488H was administered in a cumulative dosing procedure (5."	( Long-term voluntary access to running wheels decreases kappa-opioid antinociception. D'Anci, KE; Gerstein, AV; Kanarek, RB, 2000)	0.31
" Twenty-four hours later, a morphine dose-response study was conducted (tail flick); or mice were sacrificed and saturation binding studies ([3H]DAMGO) were performed in whole brain."	( The effect of nimodipine on opioid antagonist-induced upregulation and supersensitivity. Lee, SC; Yoburn, BC, 2000)	0.6
" In contrast, agonist-stimulated coupling was diminished (desensitization), resulting in a substantially flattened morphine dose-response curve."	( Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor (OP(3)) in morphine-pretreated cell. Sadée, W; Surratt, CK; Wang, D, 2000)	0.73
" Animals dosed with RB 120 (10 mg/kg) failed to develop a discriminative response."	( Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties. Fournié-Zaluski, M; Hutcheson, DM; Maldonado, R; Pache, DM; Roques, BP; Sewell, RD; Subhan, F, 2000)	0.31
" Subjects were then tested for tolerance in the distinctive context using the tail-flick procedure and dose-response curve methodology."	( Associative and non-associative fentanyl tolerance in the rat: evaluation of cross tolerance with mu-and kappa-specific opioids. Carter, BL; Conklin, CA; Tiffany, ST, 2000)	0.31
"8 mg/kg) produced a 74-fold increase in the ED(50) of morphine while showing no effect on bremazocine or BW373U86 dose-response curves."	( Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine. Broadbear, JH; Burke, TF; Husbands, SM; Lewis, JW; Sumpter, TL; Traynor, JR; Woods, JH, 2000)	0.79
" The mean titrated daily morphine dosage was 97 mg (range, 60-180)."	( Effects on cancer patients' health-related quality of life after the start of morphine therapy. Borchgrevink, PC; Kaasa, S; Klepstad, P, 2000)	0.84
"The dosage of transdermal fentanyl had to be increased on average 50% over that indicated by the manufacturer."	( Opioid treatment of painful chronic pancreatitis. Larsen, S; Madsen, LG; Niemann, T; Thorsgaard, N, 2000)	0.31
" However, the dosage often has to be increased above that recommended by the manufacturer."	( Opioid treatment of painful chronic pancreatitis. Larsen, S; Madsen, LG; Niemann, T; Thorsgaard, N, 2000)	0.31
" Dose-response and time-course determinations were performed with various opioids."	( Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the mu opioid receptor. Barrett, AC; Bowman, JR; Cook, CD; Picker, MJ; Roach, EL, 2000)	0.31
" Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form."	( Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Connors, PM; Dershwitz, M; Morishige, RJ; Rosow, CE; Rubsamen, RM; Shafer, SL; Walsh, JL, 2000)	1.45
" Furthermore, the combinations of moxonidine-morphine and clonidine-morphine resulted in substantial leftward shifts in the dose-response curves compared with those of each agonist administered separately."	( Moxonidine, a selective imidazoline-alpha2 -adrenergic receptor agonist, produces spinal synergistic antihyperalgesia with morphine in nerve-injured mice. Fairbanks, CA; Grocholski, BM; Nguyen, HO; Wilcox, GL, 2000)	0.77
" This study was conducted to determine: (1) if analgesic effects of polymer-encapsulated intrathecal adrenal chromaffin cells could be detected in the more sensitive low temperature hot-plate test without using nicotine to stimulate chromaffin cell output, (2) if a dose-response curve can be produced in the hot-plate and formalin tests with different numbers of adrenal chromaffin cells (0K, 120K, or 330K), (3) if cell viability and/or the magnitude of analgesic effects are affected by differences in implant site (i."	( Intrathecal polymer-encapsulated bovine adrenal chromaffin cells fail to produce analgesic effects in the hotplate and formalin test. Francis, JM; Lindner, MD; Saydoff, JA, 2000)	0.31
" Overall, patients in both groups requested only 25% of the permissible dosage of analgesia."	( Oral analgesia in the treatment of post-cesarean pain. Alpert, I; Itskovitz-Eldor, J; Jakobi, P; Solt, I; Weiner, Z; Zimmer, EZ, 2000)	0.31
" Three and 7 days of systemic morphine injections produced significant but unequal rightward shifts in the morphine dose-response curve such that females displayed greater increases in analgesic ED(50) values when compared to males."	( A comparison of morphine analgesic tolerance in male and female mice. Hopkins, E; Kest, B; Palmese, C, 2000)	0.94
" We conclude that periarticularly administered morphine in arthroscopic subacromial decompression in the dosage applied in this study does exert no relevant analgesic effect."	( [Effectiveness of morphine by periarticular injections after shoulder arthroscopy]. Fischer, A; Fischer, M; Henn, P; Steuer, K, 2000)	0.9
" In the presence of morphine the ACh dose-response curve was shifted to the right in a parallel fashion, suggesting a competitive interaction."	( Morphine inhibits an alpha9-acetylcholine nicotinic receptor-mediated response by a mechanism which does not involve opioid receptors. Elgoyhen, AB; Guth, PS; Holt, JC; Lioudyno, MI; Verbitsky, M, 2000)	2.07
" However, they shifted the morphine antinociceptive dose-response curve to the left when coadministered with morphine during tolerance induction, and reduced the increase in the ED50 of morphine (dose producing 50% of the maximum response) three- to four-fold."	( Intrathecal cyclooxygenase inhibitor administration attenuates morphine antinociceptive tolerance in rats. Chou, R; Chou, YY; Hsu, MM; Tung, CS; Wong, CS, 2000)	0.84
" The MOR internalization is dose-dependent, with a similar dose-response to that observed for opioid-induced increases in potassium conductance."	( Postsynaptic signaling via the [mu]-opioid receptor: responses of dorsal horn neurons to exogenous opioids and noxious stimulation. Abbadie, C; Basbaum, AI; Marek, K; Trafton, JA, 2000)	0.31
" Time- and dose-response curves were obtained in beta-endorphin-deficient and matched wild-type C57BL/6 congenic control mice using the tail-immersion/withdrawal assay."	( Disparate spinal and supraspinal opioid antinociceptive responses in beta-endorphin-deficient mutant mice. Bales, JR; Belknap, JK; Grisel, JE; Hayward, MD; Low, MJ; Mogil, JS; Rubinstein, M, 2000)	0.31
" The use of the LMA had no effect on this dose-response curve."	( Investigations using logistic regression models on the effect of the LMA on morphine induced vomiting after tonsillectomy. Anderson, BJ; Holford, NH; McGann, JE; Newson, AJ; Pearce, S, 2000)	0.54
" Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD(2."	( Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice. Campbell, WB; Fujimoto, JM; Rady, JJ, 2001)	0.58
" The intrathecal morphine antinociceptive dose-response curve (DRC) in morphine-pelleted rats was displaced to the right of that in placebo-pelleted rats, indicating antinociceptive "tolerance."	( Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. Lai, J; Malan, TP; Ossipov, MH; Porreca, F; Suenaga, NM; Vanderah, TW, 2001)	0.65
"1 times more potent during acute and chronic CO, and the E(max) values of the dose-response curves increased 35% during inflammation."	( Intestinal inflammation enhances the inhibitory effects of opioids on intestinal permeability in mice. Pol, O; Puig, MM; Valle, L, 2001)	0.31
" Toluene was not able to block morphine-induced antinocieption, however, it produced a shift of the morphine dose-response curve to lower effects, suggesting a physiological antagonism."	( Toluene increases acute thermonociception in mice. Cruz, SL; López-Rubalcava, C; Páez-Martínez, N; Pellicer, F; Salazar, LA, 2001)	0.6
" This dose-response analysis suggests that the increase in the severity of autonomic manifestations of MW is associated with a gradual activation of major structures of the autonomic nervous system."	( Sensitivity to naloxone of the behavioral signs of morphine withdrawal and c-Fos expression in the rat CNS: a quantitative dose-response analysis. Besson, JM; Gestreau, C; Le Guen, S, 2001)	0.56
" To maintain comfort, drugs were required at doses substantially above standard dosing schemes."	( Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation. Querzoli, E; Sheridan, R; Stoddard, F, )	0.13
" The time course and dose-response studies demonstrated that mu receptor phosphorylation was a rapid event, exhibited a positive dose-dependent response, and was similar to that observed in the cloned mu receptor in CHO cells."	( Agonist-induced mu opioid receptor phosphorylation and functional desensitization in rat thalamus. Deng, HB; Guang, W; Wang, H; Wang, JB; Yu, Y, 2001)	0.31
" Relative to morphine-naive control mice, significant rightward shifts in the morphine dose-response curve, resulting in increased morphine ED(50) values (approximately two to three-fold), was observed for all genotypes following three days of repeated systemic morphine injections."	( Morphine tolerance and dependence in nociceptin/orphanin FQ transgenic knock-out mice. Chen, ZP; Hopkins, E; Kest, B; Mogil, JS; Palmese, CA; Pintar, JE, 2001)	2.12
"Taken together, these data suggest that magnitude of antinociceptive tolerance is inversely related to relative efficacy of mu agonists, with lower efficacy agonists being more susceptible to tolerance than are higher efficacy agonists under these intermittent dosing conditions."	( Differential tolerance to antinociceptive effects of mu opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats. Walker, EA; Young, AM, 2001)	0.52
" When responding was maintained under the FR schedule, the dose-response curves for drugs that generalized to the training drugs were quantal in shape, while under the FI schedule, the dose-response curves for drugs that generalized to the training drugs were graded."	( Schedule control of quantal and graded dose-effect curves in a drug-drug-saline discrimination. Hardwick, WC; Li, M; McMillan, DE, 2001)	0.31
" Further research is needed to determine the time frame of exposure represented by pesticide levels in meconium and to evaluate the dose-response relationship."	( Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study. Barr, DB; Whyatt, RM, 2001)	0.31
" On the basis of the dose-response curve analysis, ohmefentanyl stereoisomers displayed a significant difference in place preference ED50."	( Quantitative comparison of ohmefentanyl isomers induced conditioning place preference in mice. Chen, XJ; Chi, ZQ; Guo, GW; Jin, WQ; Liu, ZH; Zhang, HP; Zhu, YC, 2001)	0.31
" Table 2 reviews recommended dosing of selected agents in acute coronary syndromes."	( General pharmacologic treatment of acute myocardial infarction. Harrigan, RA; Shannon, AW, 2001)	0.31
" When initiating treatment, controlled-release preparations of opioids are generally favoured, and are combined with immediate release morphine to prevent or treat 'breakthrough' pain and to enable the optimum opioid dosage to be calculated."	( [Treatment of pain in cancer with systemically administered opioids]. de Wit, R; Enting, RH; Lieverse, PJ; Smitt, PA; van der Rijt, CC; Wilms, EB, 2001)	0.51
" Dose-response curves for morphine (1."	( Repeated cocaine administration does not alter morphine-induced rotational behavior in nigrally denervated rats. Holtzman, SG; Kimmel, HL, 2001)	0.87
"Conducting complete dose-response evaluations of multiple drugs in a single within-subjects experiment is very time-consuming when a complete session is required for evaluation of each dose."	( Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action opioids in healthy volunteers. Galva, KE; Lichtor, JL; Walker, DJ; Zacny, JP, 2001)	0.31
"To evaluate a within-session cumulative-dosing procedure as a potentially efficient method for conducting dose-response evaluations of mixed-action opioids."	( Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action opioids in healthy volunteers. Galva, KE; Lichtor, JL; Walker, DJ; Zacny, JP, 2001)	0.31
"Orderly dose-response functions and replication of results of single-dosing studies confirmed that the cumulative-dosing procedure is an efficient way of determining dose-response functions for multiple opioids within the same subjects."	( Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action opioids in healthy volunteers. Galva, KE; Lichtor, JL; Walker, DJ; Zacny, JP, 2001)	0.31
" The article shows the usual dosage and "therapeutic", toxic and fatal concentrations."	( [Pharmacokinetic and toxicokinetic parameters of some drugs of abuse]. Panas, M, 2001)	0.31
" Both lorglumide and PD-135,158 induced a significant shift to the left in the morphine dose-response curves as well as a significant decrease in ED50 of the STR."	( Stimulation of either cholecystokinin receptor subtype reduces while antagonists potentiate or sensitize a morphine-induced excitatory response. Cacheiro, RG; Cruz, TN; Felicio, LF; Flório, JC; Mazzini, BK; Nasello, AG, 2001)	0.75
" The dosing intervals suggested by our study are 2 to 3 h for morphine in both rats and mice, 1 to 2 h for butorphanol in both rats and mice; and 6 to 8 h in rats and 3 to 5 h in mice for buprenorphine."	( The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice. Danneman, PJ; Gades, NM; Tolley, EA; Wixson, SK, 2000)	0.8
"Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine."	( Temporal factors affecting cocaine-opioid interactions: a cocaine drug discrimination study in rats. Green-Jordan, K; Kantak, KM; Warren, L, 2001)	1.75
" No clear dose-response effect was seen when VAS was used as a measure of pain, but it was seen when area under the curve was used as a measure of pain."	( A systematic review of the peripheral analgesic effects of intraarticular morphine. Berggren, L; Bodin, L; Gupta, A; Holmström, B, 2001)	0.54
" Second, increasing dosage of morphine often reduces pain, at the same time patients become drowsy."	( [Issues in cancer pain management]. Hoka, S; Matoba, M; Murakami, S, 2001)	0.6
" Both sexes displayed a positive dose-response relationship between acute morphine and naloxone doses and jumping frequency."	( Assessment of acute and chronic morphine dependence in male and female mice. Adler, M; Hopkins, E; Juni, A; Kest, B; Palmese, CA, 2001)	0.83
" As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine."	( Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin. Cone, EJ; Darwin, WD; Jenkins, AJ; Paul, BD; Shimomura, ET; Smith, ML; Summers, J, 2001)	0.58
" An inhibition of morphine-induced increases in dopamine could be interpreted as either antagonism or potentiation depending the shape of the morphine dose-response curve."	( Biphasic dose-related effects of morphine on dopamine release. Glick, SD; Maisonneuve, IM; Warner, LM, 2001)	0.93
" Results suggest that the pharmacokinetic properties of a drug, including the dosage administered and the rate of at which it is administered may function to jointly affect the abuse liability of the drug."	( Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans. Badger, GJ; Bickel, WK; Jonzon, B; Marsch, LA; Norsten-Höög, C; Rathmell, JP; Swedberg, MD, 2001)	0.56
" In this pilot trial of five patients with tardive and four patients with idiopathic dystonia we tested the effect of morphinsulfate in a retarded form with a dosage of 20-60 mg per day."	( Morphine in tardive and idiopathic dystonia (short communication). Becker, G; Berg, D; Naumann, M; Reiners, K, 2001)	1.75
" We used the tail-flick test to construct dose-response curves before and 4 days after chronic morphine (75-mg pellets, subcutaneously (s."	( Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice. Basbaum, AI; Gilbert, H; Malmberg, AB; Zeitz, KP, 2001)	0.77
") potentiated the cataleptic response of morphine as shown by a rightward shift in the morphine-log dose-response curve."	( Role of nitric oxide in catalepsy and hyperthermia in morphine-dependent rats. Abou Zeit-Har, MS; Afify, EA; Daabees, TT; Gabra, BH, 2001)	0.82
" Increasing morphine dosage causes drowsiness without pain improvement."	( Use of morphine and adjuvant drugs according to the condition. Matoba, M, 2001)	1.14
" (5) The rate of pain relief of patients staying in the ward where the guidance for dosing of morphine had been carried out was 37."	( Usefulness of the evidence-based medicine-supported cancer pain management guideline. Hiraga, K; Nozaki-Taguchi, N, 2001)	0.53
" The reduced dosing frequency makes the oral medication more convenient for patients, making it easier for them to comply with the dosing regimen."	( Opioid formulations: tailoring to the needs in chronic pain. Reder, RF, 2001)	0.31
" On the other hand, in male rats, castrated at postnatal days 1 and 2, the morphine dose-response curve shifted markedly to the right and, in fact, was almost identical to that observed in untreated females."	( Role of steroids in sex differences in morphine-induced analgesia: activational and organizational effects. Cicero, TJ; Meyer, ER; Nock, B; O'Connor, L, 2002)	0.81
" (when necessary) alone for chronic pain, absence of review after prescribing treatment, and lack of double dosing at night."	( An audit of morphine prescribing in a hospice. Koo, WH; Loh, EC; Neo, SH, 2001)	0.69
" Reflex contraction of the rectus abdominis in response to distension was recorded before and after cumulative dosing with the mu-opioid agonist morphine and the kappa-opioid agonist (-)U50488."	( Estrogen reduces efficacy of mu- but Not kappa-opioid agonist inhibition in response to uterine cervical distension. Eisenach, JC; Sandner-Kiesling, A, 2002)	0.52
" When dose-response curves were redetermined with a cumulative-dosing procedure, the same pattern of generalization occurred as under single-dose procedures."	( Four-choice drug discrimination in pigeons. Li, M; McMillan, DE, 2001)	0.31
" Examples for calculating required drug dosage depending on the clinical situation and the route of administration."	( [New Level III opioids of the World Health Organization]. Laval, G; Mallaret, M; Sang, B; Villard, ML, 2002)	0.31
"After an initial open titration phase aiming to determine the maximal tolerated dosage of IV morphine, the efficacy of morphine infusion (9-30 mg; mean dosage, 16 mg) was assessed in a double-blind, placebo-controlled and crossover fashion in 15 patients with poststroke- (6 patients) or spinal cord injury- (9 patients) related pain."	( Effects of IV morphine in central pain: a randomized placebo-controlled study. Attal, N; Bouhassira, D; Brasseur, L; Chauvin, M; Gaude, V; Guirimand, F, 2002)	0.89
" However, chronic morphine treatment did induce a leftward shift in the adenosine dose-response curve, indicating an increase in the sensitivity of synaptic currents to exogenously applied adenosine."	( Increase in adenosine sensitivity in the nucleus accumbens following chronic morphine treatment. Brundege, JM; Williams, JT, 2002)	0.88
" On the other hand, the bolus of intravenous clonidine 2 microg/kg (group C) was less effective in terms of pain relief but with similar side-effects to the 3 microg/kg dosage (group B)."	( Clonidine for treatment of postoperative pain: a dose-finding study. Ciccozzi, A; Di Pietro, A; Donatelli, F; Iovinelli, G; Marinangeli, F; Paladini, A; Rawal, N; Varrassi, G, 2002)	0.31
"This was a randomized, open-label, single-dose, crossover study, with a 7-day washout period between the 2 dosing days."	( Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation. Butler, J; Devane, J; Eliot, L; Loewen, G, 2002)	0.54
" Once-daily MSER approaches maximum morphine concentration more quickly, approximates maximum concentration longer, and demonstrates less fluctuation in morphine concentration during a 24-hour period than CRM dosed twice daily."	( Steady-state pharmacokinetic comparison of a new, extended-release, once-daily morphine formulation, Avinza, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain. Butler, J; Devane, J; Eliot, L; Loewen, G; Portenoy, RK; Sciberras, A, 2002)	0.82
" This study concludes that the addition of ketamine to morphine, in this dosage regimen, administered via PCAS for postoperative pain control, does not confer benefit following total abdominal hysterectomy."	( Effect of the addition of ketamine to morphine in patient-controlled analgesia. Crooks, BA; Miller, CD; Murdoch, CJ, 2002)	0.83
" Pain therapy was continued by infusion and PCA with morphine in a daily intravenous dosage of 600-800 mg."	( [Postoperative morphine excess or rational therapy? An exceptional case of applying the morphine equivalent]. Eysel, P; Heid, F; Jage, J, 2002)	0.92
" The main principles of post-operative dosing and logistic pitfalls are illustrated."	( [Postoperative morphine excess or rational therapy? An exceptional case of applying the morphine equivalent]. Eysel, P; Heid, F; Jage, J, 2002)	0.67
" Clocinnamox (10 mg/kg) produced a 7- and 12-fold further decrease in morphine and fentanyl potency, respectively, a reduction in the slope of the morphine dose-response curve, and a suppression of the maximal morphine responding for buprenorphine."	( Clocinnamox distinguishes opioid agonists according to relative efficacy in normal and morphine-treated rats trained to discriminate morphine. Walker, EA; Young, AM, 2002)	0.77
"To evaluate the adequacy of as-needed (prn) dosing of narcotics during the acute postoperative period following laryngectomy and to evaluate the role of nurses' interpretation and implementation of narcotic orders in postoperative pain management."	( Acute pain management following laryngectomy. Krempl, GA; Medina, JE; Orgill, R, 2002)	0.31
"All physician orders for narcotics were at or above the minimum dosing guidelines; 68% met a recommended adequate postoperative prescription for moderate pain."	( Acute pain management following laryngectomy. Krempl, GA; Medina, JE; Orgill, R, 2002)	0.31
"As-needed dosing of analgesia resulted in suboptimal pain control for at least 35% of patients undergoing laryngectomy."	( Acute pain management following laryngectomy. Krempl, GA; Medina, JE; Orgill, R, 2002)	0.31
" The only sensitive study of four dose-response comparisons indicated that 5mg of IA morphine was more effective than 1mg."	( No pain, no gain: clinical excellence and scientific rigour--lessons learned from IA morphine. Kalso, E; McQuay, HJ; Moore, AR; Smith, L, 2002)	0.76
" Random regression modeling was used to simultaneously estimate the effect of randomized group assignment, actual morphine dose (protocol dosage plus extra morphine when required), age category, surgical stress, and the time-varying covariate mechanical ventilation on COMFORT 'behavior' and the observational VAS rated pain, respectively."	( Efficacy of continuous versus intermittent morphine administration after major surgery in 0-3-year-old infants; a double-blind randomized controlled trial. Bouwmeester, NJ; de Boer, JB; Duivenvoorden, HJ; Koot, HM; Passchier, J; Tibboel, D; van Dijk, M, 2002)	0.79
" Individuals exposed to opioid treatment for pain management during surgical procedures or maintained on oral methadone for treatment of drug addiction show either no effect or a suppressed immune system, depending on dosage and, in the case of methadone-maintained patients, duration of drug treatment."	( Opioids, immunology, and host defenses of intravenous drug abusers. Alonzo, NC; Bayer, BM, 2002)	0.31
" Using a mouse hot-plate test, dose-response relationships were first determined for all compounds individually and then for opioids co-administered with fixed doses of ketamine or dextromethorphan."	( Dextromethorphan and ketamine potentiate the antinociceptive effects of mu- but not delta- or kappa-opioid agonists in a mouse model of acute pain. Baker, AK; Hoffmann, VL; Meert, TF, 2002)	0.31
"Systemic opioid dosing until adequate analgesia in neuropathic pain may involve intolerable and untreatable side effects."	( The glycine/NMDA receptor antagonist (+)-HA966 enhances the peripheral effect of morphine in neuropathic rats. Christensen, D; Kayser, V; Martinez, V, 2002)	0.54
" No sign of physical or psychological dependence was observed during the period of opiate administration, and no withdrawal phenomenon was found as the dosage was tapered."	( Long-term opioid treatment in Behçet's syndrome with intractable abdominal pain--a case report. Chang, Y; Chen, JY; Lee, CL; Swei, SC; Tseng, HC; Wen, YR; Wu, GJ, 2002)	0.31
"Morphine antinociceptive activity was tested twice, before and after chronic morphine administration, in the tail-flick test using a cumulative dose-response protocol."	( Inhibitory effects of MPEP, an mGluR5 antagonist, and memantine, an N-methyl-D-aspartate receptor antagonist, on morphine antinociceptive tolerance in mice. Kozela, E; Pilc, A; Popik, P, 2003)	1.97
" The colon hyperalgesia persisted for 14 days and was associated with a significant shift of the morphine dose-response function to the left."	( Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice. Gebhart, GF; Jones, RC; Kamp, EH; Tillman, SR, 2003)	0.54
" Ten to fifty micrograms of BmK venom was deemed to be a sufficient dosage to evoke c-Fos expression."	( c-Fos expression in rat spinal cord induced by scorpion BmK venom via plantar subcutaneous injection. Bai, ZT; Chen, B; Fan, GL; Ji, YH; Zhang, XY, 2002)	0.31
" A pre-defined dosing algorithm permitted initial titration of the opioids to predetermine the optimal level of sedation and pain score."	( Remifentanil vs morphine for patients in intensive care unit who need short-term mechanical ventilation. Chinachoti, T; Kessler, P; Kirkham, A; Werawatganon, T, 2002)	0.66
" Using a mouse hot-plate test, dose-response relationships were first determined for all compounds individually and then for opioids co-administered with fixed doses of clonidine, ketamine or dextromethorphan."	( Interactions of NMDA antagonists and an alpha 2 agonist with mu, delta and kappa opioids in an acute nociception assay. Baker, AK; Hoffmann, VL; Meert, TF, 2002)	0.31
"From the population pharmacokinetic model presented, CSF concentration profiles can be derived for M, M3G and M6G on the basis of dosing information and creatinine clearance without collecting CSF samples."	( Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine. Brockmöller, J; Freudenthaler, S; Gleiter, CH; Hofmann, U; Meineke, I; Mikus, G; Prange, HW; Schaeffeler, E; Schwab, M, 2002)	0.61
" In these studies, we first constructed antinociceptive dose-response curves for Dex and morphine (MSO4)."	( Dexmedetomidine fails to cause hyperalgesia after cessation of chronic administration. Clark, JD; Davies, MF; Haimor, F; Lighthall, G, 2003)	0.54
" Self-regulated dosing of morphine is also associated with rapid escalation of daily consumption and no significant alterations in consumption rates."	( Subject-regulated dosing alters morphine self-administration behavior and morphine-stimulated [35S]GTPgammaS binding. Chen, AC; Kreek, MJ; Kruzich, PJ; Unterwald, EM, 2003)	0.9
" Both dose-response analyses and the determination of the strength of the reinforcing properties of opiates using a "breakpoint" analysis were examined."	( Gender differences in the intravenous self-administration of mu opiate agonists. Aylward, SC; Cicero, TJ; Meyer, ER, 2003)	0.32
" The dosage of the two comparatine groups is given according to Documentation, the method of abserving the treatment protocols and detoxification standard is according to current regulation."	( [Clinial study of "qingjunyin" detoxification for the treatment of heroin addicts]. Lan, S; Lu, H; Wang, G; Yuan, D; Zhan, C, 1997)	0.3
"Morphine dosage [median (25th-75th percentiles)] was less in the first 24 h in the patients who were given intrathecal morphine + clonidine [7 (0-37) mg] than in other patients [40."	( Intrathecal morphine and clonidine for coronary artery bypass grafting. Arnulf, JJ; Balarac, N; Bonnet, F; Lena, P; Teboul, J, 2003)	2.14
"We sought to investigate the dose-response relationship for the effect of intrathecal morphine on the transient spastic paraparesis after short-lasting spinal ischemia in rats."	( Intrathecal administration of morphine, but not small dose, induced spastic paraparesis after a noninjurious interval of aortic occlusion in rats. Cousins, MJ; Fuchigami, T; Kakinohana, M; Kawabata, T; Nakamura, S; Sasara, T; Sugahara, K, 2003)	0.83
" All mu and delta(2) agonists tested had similar maximal effects on phagocytosis, and all dose-response curves suggest positive cooperativity."	( Mu and delta receptors mediate morphine effects on phagocytosis by murine peritoneal macrophages. Loh, HH; Renaud, FL; Roy, S; Tomassini, N, 2003)	0.6
"The influence of morphine dosing time on analgesic effect after acute or chronic treatment, recovery of analgesic effect after once developed tolerance, and their pharmacological mechanisms were investigated in ICR male mice under a 12-h light/dark cycle (light on from 7:00 AM to 7:00 PM)."	( Chronopharmacology of analgesic effect and its tolerance induced by morphine in mice. Higuchi, S; Matsuo, A; Ohdo, S; Takane, H; Tomiyoshi, Y; Yoshida, M; Yukawa, E, 2003)	0.89
" The dose-response curve of morphine (1."	( A persistent opioid-addiction state of memory. Bruins Slot, LA; Colpaert, FC, 2003)	0.61
" Morphine exhibited a bell-shaped dose-response curve in Lewis rats, these animals being more sensitive than F344 at 1 and 5 mg/kg but less sensitive at 10 mg/kg."	( The contribution of alpha2-adrenoceptor and opioid receptor mechanisms to antinociception differs in Lewis and Fischer 344 rats. Alguacil, LF; Herradón, G; Morales, L; Pérez-García, C, 2003)	1.23
" As a positive control, morphine was infused at a dosage that definitely produced CNS effects."	( Peripheral opioid analgesia in experimental human pain models. Burian, M; Geisslinger, G; Lötsch, J; Meier, S; Schmidt, H; Tegeder, I, 2003)	0.63
"A dosage of rectal paracetamol 1000 mg four times daily is too low, as all displayed a suboptimal serum paracetamol concentration."	( Randomized, double-blind, placebo-controlled study of the effect of rectal paracetamol on morphine consumption after abdominal hysterectomy. Borchgrevink, PC; Dale, O; Hagen, L; Kvalsvik, O, 2003)	0.54
" A relatively flat dose-response relationship was observed, which did not increase monotonically with morphine dose."	( A new progressive ratio schedule for support of morphine self-administration in opiate dependent rats. Delich, J; Glowa, J; Grasing, K; He, S; Li, N; Parrish, C, 2003)	0.79
" Dose-response studies indicated that c-Fos protein expression was induced at doses (0."	( The novel analgesic and high-efficacy 5-HT1A receptor agonist, F 13640 induces c-Fos protein expression in spinal cord dorsal horn neurons. Besson, JM; Buritova, J; Colpaert, F; Tarayre, JP, 2003)	0.32
" Measuring rectal body temperatures, dose-response relationships were established for all compounds."	( Morphine and d-amphetamine nullify each others' hypothermic effects in mice. Baker, A; Meert, T, 2003)	1.76
" Using three human cancer cell lines: MIA PaCa-2 pancreatic adenocarcinoma, HT-29 colon adenocarcinoma, and CAL-27 squamous cell carcinoma of the head and neck, and OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6)M) selected because it is known to repress or increase, respectively, cell replication, the effects on apoptosis (TUNEL, Annexin V) and necrosis (trypan blue) were investigated on days 2, 5, and 7 of exposure."	( Opioids and the apoptotic pathway in human cancer cells. McLaughlin, PJ; Zagon, IS, 2003)	0.32
" However, patients might have a better outcome with a reduction of morphine dosage and administration of a muscle relaxant of shorter duration of action than pancuronium."	( A randomized trial of caudal block with bupivacaine 4 mg x kg-1 (1.8 ml x kg-1) plus morphine (150 microg x kg-1) vs general anaesthesia with fentanyl for cardiac surgery. Castillo-Zamora, C; Nava-Ocampo, AA; Rojas-Pérez, E, 2003)	0.78
"), which produced a significant shift to the right of the morphine dose-response curve."	( Role of Na(+), K(+)-ATPase in morphine-induced antinociception. Agil, A; Baeyens, JM; Del Pozo, E; Horvath, G; Masocha, W; Ocana, M; Szikszay, M, 2003)	0.85
" It is currently debated if the steep ascending part of the biphasic dose-response curve typically obtained in multiple-dosing lever-press-based operant conditioning procedures represents a satiety-driven, all-or-none response or if the response is gradual and tightly adjusted to the various doses of the reinforcer."	( Opioids, cocaine, and food change runtime distribution in a rat runway procedure. Saria, A; Sturm, K; Wakonigg, G; Zernig, G, 2003)	0.32
" Rats were then anesthetized, and the electromyographic response in the rectus abdominis muscle to UCD was recorded in the absence and presence of cumulative dosing with intrathecal morphine."	( Intrathecal morphine reduces the visceromotor response to acute uterine cervical distension in an estrogen-independent manner. Eisenach, JC; Shin, SW, 2003)	0.89
" Rescue dosing was less than recommended, in relation to prescribed transdermal fentanyl strength in 21 patients (60 percent) and greater than recommended in one patient (3 percent)."	( Breakthrough strong opioid analgesia prescription in patients using transdermal fentanyl admitted to a hospice. Lawrie, I; Lloyd-Williams, M; Waterhouse, E, )	0.13
" Nowadays the chronic use of oral morphine preparations has been supported by medical authorities who at the same time warn against incorrect dosage and combination with other drugs."	( [Morphine--myths and facts]. Andres, J; Macheta, A; Weber, T; Zawiła, K, 2001)	1.5
" The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days."	( Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. Alston, RP; Duke, PC; Feneck, RO; Hsu, PH; Hubbard, RC; Mangano, DT; Nussmeier, NA; Ott, E; Saidman, LJ; Snabes, MC, 2003)	0.32
" The present study was designed to determine the extent to which D2/3 receptor activation and blockade can modulate morphine-induced locomotion using a novel cumulative dosing procedure in Swiss-Webster mice."	( The modulatory actions of dopamine D2/3 agonists and antagonists on the locomotor-activating effects of morphine and caffeine in mice. Beardsley, PM; Cook, CD, 2003)	0.74
" Additionally, a 1 ml bolus dosage was administered at a 60-minute lockout interval employing a pump which contained 36 mg of morphine hydrochloride, 30 mg of metoclopramide hydrochloride in 62 ml of physiologic saline."	( Utilization of PCIA (patient-controlled intravenous analgesia) for postoperative analgesia of spine fusion. Hasegawa, J; Hirasawa, M; Nishiyama, J; Suzuki, T, 2003)	0.53
") pretreatment with PI3K inhibitors at the dosage that suppressed the morphine-induced supraspinal antinociception."	( [Direct involvement of the supraspinal phosphoinositide 3-kinase/phospholipase C gamma 1 pathway in the mu-opioid receptor agonist-induced supraspinal antinociception in the mouse]. Narita, M, 2003)	0.55
" The prescription should also then be individualised as to the route of administration, dosage, dosage form, frequency, and duration of the medication being prescribed."	( Individualising therapy. The right dose, dosage form, frequency and duration. George, A; Shakib, S, 2003)	0.32
"Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting."	( Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. Abernethy, AP; Bui, C; Currow, DC; Fazekas, BS; Frith, P; McHugh, A, 2003)	0.85
" After responding stabilized, dose-response curves were determined for other drugs."	( Retention of sequential drug discriminations under fixed-interval schedules for long time periods without training. Li, M; McMillan, DE, 2003)	0.32
" Demerol in small dosage is safe and effective."	( An evaluation of obstetrical analgesia. FIST, HS, 1954)	0.23
"The respiration of KCl-stimulated cortical slices of brain from control rats is markedly depressed by morphine, whereas the respiration of those from rats chronically dosed with morphine is unaffected."	( Cellular adaptation to morphine in rats. TAKEMORI, AE, 1961)	0.77
" In the first block (n=10) a dose-response relationship for topical morphine was found."	( Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study. Bonomi, MR; Cerchietti, LC; Cohen, AM; Körte, MW; Navigante, AH; Quiroga, PN; Roth, BM; Villaamil, EC, 2003)	0.8
" The incidence of intraoperative supplemental analgesic and hypotension and the dosage of ephedrine used to treat hypotension were greater in the patients anesthetized with tetracaine 10 mg than in those anesthetized with bupivacaine 10 mg, which is equipotent to tetracaine 10 mg."	( [Spinal anesthesia using hyperbaric bupivacaine HCl for cesarean section]. Fukumitsu, K; Haruna, J; Hirao, O; Kawaraguchi, Y; Kinouchi, K; Kitamura, S; Matsuda, Y; Miyamoto, Y; Nakao, F; Taniguchi, A, 2003)	0.32
"2% in oxygen and nitrous oxide and the opioid dosing was titrated to autonomic responses."	( Remifentanil infusion for cleft palate surgery in young infants. Dagher, C; Desjeux, L; Gall, O; Murat, I; Roulleau, P, 2003)	0.32
"Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6."	( Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence. Bochner, F; Mitchell, TB; Somogyi, AA; White, JM, 2003)	0.74
"In this article we described a 15-year-old female who was admitted to the Clinic of Toxicology because of suicidal, oral intoxication with morphine sulphate in the total dosage of 360 mg."	( [Non-invasive positive pressure respiration in acute respiratory failure caused by suicidal oral intoxication with morphine sulphate]. Anand, JS; Chodorowski, Z; Wujtewicz, M, 2003)	0.73
" This may hinder adequate dosing in cancer pain."	( Oral morphine and respiratory function amongst hospice inpatients with advanced cancer. Kaiko, R; Rivera, NI; Walsh, TD, 2003)	0.83
" Oral morphine given repeatedly in individualized dosage is a safe and efficacious analgesic in the majority of those with advanced cancer."	( Oral morphine and respiratory function amongst hospice inpatients with advanced cancer. Kaiko, R; Rivera, NI; Walsh, TD, 2003)	1.31
" Sustained release versions of morphine were effective for 12 or 24 hour dosing depending on the formulation."	( Oral morphine for cancer pain. Barden, J; Edwards, JE; McQuay, HJ; Wiffen, PJ, 2003)	1.12
" Dose-response curves for buprenorphine-induced antinociception display ceiling effects or are bell shaped, which have been attributed to the partial agonist activity of buprenorphine at opioid receptors."	( Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. Bryant, CD; Carroll, FI; Eitan, S; Evans, CJ; Kieffer, BL; Lutfy, K; Maidment, NT; Saliminejad, N; Takeshima, H; Walwyn, W; Yang, YC, 2003)	0.32
" The search showed sparse empirical work warranting endorsement of this dosing regimen."	( Time-contingent schedules for postoperative analgesia: a review of the literature. Craig, KD; Pillai Riddell, RR, 2003)	0.32
"The dosage of intrathecal morphine that provides the best balance between analgesic efficacy and side effect profile in the older patient undergoing hip arthroplasty is not known."	( Optimizing the dose of intrathecal morphine in older patients undergoing hip arthroplasty. Kinirons, B; Laffey, JG; Murphy, PM; Stack, D, 2003)	0.9
" 5-HT-evoked scratching was significantly reduced by systemic administration of the opiate antagonist naltrexone but was not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia."	( Opioid modulation of scratching and spinal c-fos expression evoked by intradermal serotonin. Carstens, E; Carstens, MI; Cuellar, JM; Moore, JA; Nojima, H; Simons, CT, 2003)	0.52
" With appropriate opioid adjustment--in this case reduction of intrathecal morphine dosage by a factor of 100--the condition rapidly resolved and the patient became pain-free and remained so until his death six weeks later."	( Morphine hyperalgesia: a case report. Reisfield, GM; Wilson, GR, )	1.8
" In the second protocol, plasma morphine and glucuronide metabolite concentrations and pupil diameters were evaluated after oral morphine administration (30 mg), dosed 1 hour after oral quinidine (600 mg) or placebo."	( Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Hoffer, C; Kharasch, ED; Sheffels, P; Whittington, D, 2003)	0.83
"Consumed amount of narcotics per day and the course of dosage of injectable heroin in different treatment regimes."	( Dosage regimes in the prescription of heroin and other narcotics to chronic opioid addicts in Switzerland--Swiss national cohort study. Blättler, R; Bürki, C; Christen, S; Gschwend, P; Gutzwiller, F; Rehm, J; Seidenberg, A; Steffen, T, 2004)	0.32
" The mean daily dosage was 474 mg for intravenous application and 993 mg for the smokeable form."	( Dosage regimes in the prescription of heroin and other narcotics to chronic opioid addicts in Switzerland--Swiss national cohort study. Blättler, R; Bürki, C; Christen, S; Gschwend, P; Gutzwiller, F; Rehm, J; Seidenberg, A; Steffen, T, 2004)	0.32
" dosing of mice with 1 for 1 week developed tolerance in a similar manner to that of morphine in TF and HP tests, implicating that 1 also acts through a similar mechanism analogous to morphine at mu-opioid receptors."	( Novel 2',6'-dimethyl-L-tyrosine-containing pyrazinone opioid mimetic mu-agonists with potent antinociceptive activity in mice. Ambo, A; Bryant, SD; Jinsmaa, Y; Lazarus, LH; Okada, Y; Sasaki, Y; Shiotani, K; Tsuda, Y, 2004)	0.55
", the dose-response curves for morphine analgesia in Hargreaves thermal test were shifted rightward in partial sciatic nerve-injured mice compared with control sham-operated mice."	( Loss of peripheral morphine analgesia contributes to the reduced effectiveness of systemic morphine in neuropathic pain. Inoue, M; Rashid, MH; Toda, K; Ueda, H, 2004)	0.94
"Opioid dosing strategies for acute pain differ from strategies for chronic pain management."	( Acute pain in advanced cancer: an opioid dosing strategy and illustration. Davis, MP, )	0.13
" Naloxone, which had no effect on the dextromethorphan dose-response relation, abolished the synergism."	( Morphine potentiates dextromethorphan-induced vasodilation in rat superior mesenteric artery. Inan, S; Tallarida, RJ, 2004)	1.77
" Naloxone 2 mg by gastric tube every 8 hours for 8 days was started; the dosage then was increased to 4 mg every 8 hours."	( Enteral administration of naloxone for treatment of opioid-associated intragastric feeding intolerance. Bloom, K; Liebl, MG; Mixides, G, 2004)	0.32
"Several studies indicate greater sensitivity to morphine (MOR) analgesia in male compared to female rats under the acute dosing condition."	( Morphine tolerance in male and female rats. Holtman, JR; Sloan, JW; Wala, EP, 2004)	2.02
" This dosage form presents the clinical advantage of less frequent dosing, with increased quality of life for patients."	( Comparative study of morphine diffusion from sustained release polymeric suspensions. Calpena, AC; Doménech, J; Gallardo Lara, V; Morales, ME; Ruiz, MA, 2004)	0.64
"-M at a dose equivalent to 20% of the basal oral dosage is safe and effective in the majority of patients experiencing pain exacerbation."	( Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose. Bianchi, M; Casuccio, A; Ferrera, P; Mercadante, S; Villari, P, 2004)	0.59
" The recommended initial dosage was 30 mg every 12 hours, and then the dosage was regulated according to the effects until the ideal anesthesia was achieved."	( [Effects of sustained release morphine hydrochloride tablets in management of cancer pain: a survey of 567 patients]. Chen, J; Chen, LZ; Ma, ZS; Ma, ZY; Qiu, H; Wang, DL; Yu, SY; Zhang, Y, 2004)	0.61
"1% of the patients received a dosage	( [Effects of sustained release morphine hydrochloride tablets in management of cancer pain: a survey of 567 patients]. Chen, J; Chen, LZ; Ma, ZS; Ma, ZY; Qiu, H; Wang, DL; Yu, SY; Zhang, Y, 2004)	0.61
" Sustained release morphine hydrochloride is worth recommending as a first-line drug for the treatment of patients with moderate to severe cancer pain, and the usually dosage is 120 mg or less per day."	( [Effects of sustained release morphine hydrochloride tablets in management of cancer pain: a survey of 567 patients]. Chen, J; Chen, LZ; Ma, ZS; Ma, ZY; Qiu, H; Wang, DL; Yu, SY; Zhang, Y, 2004)	0.94
" Repetitive dosing with ethosuximide (i."	( Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Bennett, GJ; Flatters, SJ, 2004)	0.32
" Separate groups of animals at each interval between morphine and naloxone received cumulative naloxone dosing after all morphine pretreatments (NAL ALL DAYS) or after just the first and last morphine pretreatment (NAL FIRST/LAST)."	( Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence. Liu, J; Morse, AC; Schulteis, G, 2004)	0.57
" Naltrexone produced significant and surmountable dose-dependent rightward shifts in the morphine dose-response curves for both groups, but did not differ in potency across diets."	( Naltrexone antagonism of morphine antinociception in sucrose- and chow-fed rats. D'Anci, KE; Kanarek, RB, 2004)	0.85
" Fixed interval dosing schedules conducted over several days are associated with a high risk of serious morbidity and mortality."	( Methadone for cancer pain. Nicholson, AB, 2004)	0.32
" As the fentanyl dosage was excessive even in some patients who followed the recommended morphine/fentanyl conversion of 150:1, it is dangerous to use the conversion ratio of 78:1 at first."	( A study of transdermal fentanyl in cancer pain at Aichi-Cancer Center. Hasegawa, M; Hosoda, R; Kamiya, Y; Kato, K; Mizaki, T; Nitta, M; Yamazaki, S, 2004)	0.55
" Fourteen patients receiving strong opioids who had increased their dosage more than 100% in the last week unsuccessfully were randomly chosen to add a second opioid to the first using an initial equivalent dosage of 20% of the previous therapy."	( Addition of a second opioid may improve opioid response in cancer pain: preliminary data. Casuccio, A; Ferrera, P; Mercadante, S; Villari, P, 2004)	0.32
" No relationship between morphine dosing and cortisol response was demonstrated in these infants."	( Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months. Grunau, RE; Weinberg, J; Whitfield, MF, 2004)	0.63
" Here we examined whether enhanced inflammation and END expression within the synovial tissue of patients undergoing arthroscopic knee surgery might shift the analgesic dose-response curve of intra-articular (i."	( Increased numbers of opioid expressing inflammatory cells do not affect intra-articular morphine analgesia. Koppert, W; Likar, R; Mousa, SA; Philippitsch, G; Schäfer, M; Stein, C; Steinkellner, H, 2004)	0.55
" These dose-response relationships were not different between patients with low versus high numbers of inflammatory and END-containing synovial cells (P>0."	( Increased numbers of opioid expressing inflammatory cells do not affect intra-articular morphine analgesia. Koppert, W; Likar, R; Mousa, SA; Philippitsch, G; Schäfer, M; Stein, C; Steinkellner, H, 2004)	0.55
"The objective of this study was to determine if judicious dosing of morphine sulfate can provide pain relief without changing important physical examination findings in patients with acute appendicitis."	( Does morphine change the physical examination in patients with acute appendicitis? Fiallo, V; Garb, JL; Montano, G; Phipen, S; Smithline, HA; Wolfe, JM, 2004)	1.07
" It also caused a shift in the morphine antinociceptive dose-response curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response)."	( Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats. Chen, YJ; Lee, TH; Liu, JK; Lu, CY; Tsai, YJ; Wang, CH; Yang, LC, 2004)	0.86
" Timing of administration, inadequate dosing and possible altered pharmacokinetics in pregnancy may explain the lack of efficacy."	( The effect of celecoxib on intrathecal morphine-induced pruritus in patients undergoing Caesarean section. Irwin, MG; Lee, LH; Lim, J; Wong, CK, 2004)	0.59
" ACTH levels in response to the last morphine injection of the repeated dosage regimen were found to be lower compared to those in acutely morphine-treated mice."	( Behavioral sensitization to intermittent morphine in mice is accompanied by reduced adrenocorticotropine but not corticosterone responses. Jezova, D; Makara, GB; Mlynarik, M; Zelena, D, 2004)	0.86
" Furthermore, the differences between intermittent and continuous dosing protocols were evaluated."	( Opioid agonist and antagonist treatment differentially regulates immunoreactive mu-opioid receptors and dynamin-2 in vivo. Patel, K; Purohit, V; Yoburn, BC; Zhang, Q, 2004)	0.32
" Morphine dosage was found to be inversely correlated (r) with age (r = -0."	( Patterns of high-dose morphine use in a home-care hospice service: should we be afraid of it? Adunsky, A; Bercovitch, M, 2004)	1.55
" On Day 8, an antinociceptive dose-response curve was constructed and the 50% effective dose (ED(50)) values for morphine (given alone) were calculated for each study group."	( The effects of intrathecal gabapentin on spinal morphine tolerance in the rat tail-flick and paw pressure tests. Gilron, I; Hansen, C; Hong, M, 2004)	0.79
"We examined the dose-response relationship of intrathecal clonidine at small doses (	( Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery: a dose-response study. Aeschbach, A; Gurzeler, JA; Kindler, CH; Schneider, MC; Strebel, S, 2004)	0.32
" In the present study, (B6 x 129)F2 hybrid mice were given daily morphine injections for four days using an escalating dosing schedule, and naloxone-precipitated withdrawal on day 5 was measured."	( Mapping of a quantitative trait locus for morphine withdrawal severity. Chesler, EJ; Juni, A; Kest, B; Mogil, JS; Palmese, CA, 2004)	0.83
" Research efforts to find the most appropriate route and dosage of morphine for dyspnea, based on the patient's situation, remain worthwhile."	( Morphine for dyspnea control in terminal cancer patients: is it appropriate in Taiwan? Chen, CY; Cheng, SY; Chiu, TY; Hu, WY, 2004)	2
" Withdrawal scores at the time of dosing were higher in the TOP patients (9."	( Comparison of tincture of opium and methadone to control opioid withdrawal in a Thai treatment centre. Ali, R; Bochner, F; Foster, DJ; Jittiwutikarn, J; Somogyi, AA; White, JM, 2004)	0.32
" Patients were then crossed over for 7 days of treatment at an estimated equianalgesic dosage of oxymorphone ER."	( Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: a pilot study. Ahdieh, H; Slatkin, N; Sloan, P, 2005)	0.33
") dose of morphine significantly prolonged the time mice spent in drug-paired compartment compared with saline, but there was no dose-response relation."	( [Establishment of computer-based video-tracking conditioned place preference experiment system in mice]. Chen, HH; Long, ZH; Zhou, LF; Zhu, YP, 2004)	0.73
" First-line treatment was sustained-release morphine sulfate in a mean starting dosage of 55."	( Tolerability of opioids in patients with acute pain due to nonmalignant musculoskeletal disease. A hospital-based observational study. Cherasse, A; Maillefert, JF; Muller, G; Ornetti, P; Piroth, C; Tavernier, C, 2004)	0.58
" Long-acting oral opioids supply satisfactory analgesia at more convenient dosing intervals."	( Advances in opioid therapy and formulations. Walsh, D, 2005)	0.33
" Fluoxetine applied in 5 mg/kg dosage causes increased pain reaction 60 and 90 minutes (p=0."	( Testing of analgesic effect of fluoxetine. Becić, F; Begović, A; Zulić, I, 2004)	0.32
" CCK in the RVM also acutely displaced the spinal morphine antinociceptive dose-response curve to the right."	( Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. Gardell, LR; Herman, DS; Lai, J; Ossipov, MH; Porreca, F; Stiller, CO; Vanderah, TW; Xie, JY, 2005)	0.58
" Most patients (68%) chose once-daily dosing for continuing pain management (P=0."	( Efficacy, safety, and steady-state pharmacokinetics of once-a-day controlled-release morphine (MS Contin XL) in cancer pain. Darke, A; Eisenhoffer, J; Hagen, NA; Harsanyi, Z; Quigley, P; Thirlwell, M, 2005)	0.55
" Morphine and R-PIA were administered to obtain the dose-response curve and the 50% effective dose (ED(50))."	( Morphine can enhance the antiallodynic effect of intrathecal R-PIA in rats with nerve ligation injury. Cho, SK; Han, SM; Hwang, GS; Hwang, JH, 2005)	2.68
" In the second part, a 40:3 tramadol:morphine dosing ratio was used."	( The median effective dose of tramadol and morphine for postoperative patients: a study of interactions. Benhamou, D; Marcou, TA; Marque, S; Mazoit, JX, 2005)	0.87
" Initial morphine dosing may be guided by age and weight, but clearance and distribution volume changes (and their variability) during prolonged ECMO suggests that morphine therapy should be subsequently guided by clinical monitoring."	( Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Anderson, BJ; Peters, JW; Simons, SH; Tibboel, D; Uges, DR, 2005)	2.19
" ICR mice were used to generate full antagonist dose-response curves for naloxone, naltrexone, nalbuphine, and 6beta-naltrexol in blocking acute antinociceptive effects of morphine and precipitating opioid withdrawal in models of physical dependence."	( In vivo characterization of 6beta-naltrexol, an opioid ligand with less inverse agonist activity compared with naltrexone and naloxone in opioid-dependent mice. Bhamidipati, CM; Bilsky, EJ; Blair, JR; Lowery, JJ; Paolino, RM; Raehal, KM; Sadée, W; Wang, D, 2005)	0.52
" Tolerance developed to hyperalgesia following repeated (chronic) dosing with low dose morphine."	( Characterization of morphine-induced hyperalgesia in male and female rats. Holtman, JR; Wala, EP, 2005)	0.87
" dosing contributes to the hastened development of analgesic tolerance seen in these animals."	( Transcriptional and translational regulation of glial activation by morphine in a rodent model of neuropathic pain. DeLeo, JA; LaCroix-Fralish, ML; Nutile-McMenemy, N; Tawfik, VL, 2005)	0.56
" Week 2 dosage was increased, decreased, or maintained depending on response and side effects."	( Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder. Aboujaoude, E; Bullock, KD; Elliott, M; Franz, B; Gamel, N; Koran, LM, 2005)	0.61
" The 35- to 37-kDa isoforms of deltaFosB, also referred to as the chronic Fras, were measured in the nucleus accumbens, caudate putamen, and frontal cortex of male Sprague-Dawley rats after either an acute injection of morphine or an escalating dosing schedule of morphine for 10 days."	( D1 dopamine receptors modulate deltaFosB induction in rat striatum after intermittent morphine administration. Muller, DL; Unterwald, EM, 2005)	0.74
" This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery."	( A comparison of Depodur, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. Gambling, D; Horton, W; Hughes, T; Manvelian, G; Martin, G, 2005)	0.56
" Visual analog scale pain scores at rest and with activity at 24 to 48 h after dosing were significantly better in the 10- and 15-mg single-dose EREM groups versus the standard morphine group."	( Single-dose, sustained-release epidural morphine in the management of postoperative pain after elective cesarean delivery: results of a multicenter randomized controlled study. Carvalho, B; Cohen, SE; Gambling, D; Huffnagle, HJ; Lihou, C; Manvelian, G; Muir, H; Palmer, C; Polley, L; Riley, E; Segal, S, 2005)	0.79
" In conclusion, from the above results one may suggest that, in determination of the dose-response of at least some drugs, the study of the effects of doses much lower than two orders of magnitude of the minimum effective dose are warranted."	( Effects of ultra-low doses of morphine, naloxone and ethanol on morphine state-dependent memory of passive avoidance in mice. Djahanguiri, B; Tayebi Meybodi, K; Vakili Zarch, A; Zarrindast, MR, 2005)	0.62
" Duration and intensity of uterine contractions also showed a positive dose-response relationship."	( Dose minimization study of oxytocin in early labor in sows: uterine activity and fetal outcome. Alonso-Spilsbury, YM; Martínez-Burnes, J; Mota-Rojas, D; Nava-Ocampo, AA; Ramírez-Necoechea, R; Trujillo, ME; Velázquez-Armenta, Y, )	0.13
" Analgesia was assessed using a standard hot plate protocol and dose-response cumulative curves for morphine analgesia were obtained on days 1 and 11."	( Environmental and intraperitoneal ethanol influences morphine antinociceptive effect in mice. de la Parte, JF; Hernández, PZ; Peiró, AM; Peris, LC, 2005)	0.79
" In addition, the dose-response effect of the morphine-induced rewarding effect was dramatically attenuated in cdk5 heterozygous (+/-) knockout mice."	( Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine. Nagumo, Y; Narita, M; Shibasaki, M; Suzuki, T; Yajima, Y, 2005)	0.79
" The effective dose that produced 50% antinociception (ED(50)) was calculated from the log dose-response curve of intrathecally administered fixed ratio combinations of morphine with each NSAID."	( Spinal synergy between nonselective cyclooxygenase inhibitors and morphine antinociception in mice. Miranda, HF; Pinardi, G; Prieto, JC, 2005)	0.76
"7 mg/kg) rats, the morphine dose-response curve was shifted to the right in burn-injured rats (4."	( A rat model of unilateral hindpaw burn injury: slowly developing rightwards shift of the morphine dose-response curve. Jeevendra Martyn, JA; Lim, G; Mao, J; Sung, B; Wang, S; Yang, L; Zeng, Q, 2005)	0.88
" The present studies examined whether systemic administration could be effective in attenuating morphine tolerance in non-injured rodents using a similar dosing paradigm."	( Systemic administration of propentofylline does not attenuate morphine tolerance in non-injured rodents. Forsayeth, JR; Johnson, KW; Samuels, I; Shumilla, JA, 2005)	0.79
"Baseline (vehicle dosed animals) gastrointestinal transit was significantly greater in fasted versus fed rats."	( Effects of fasting on evaluation of gastrointestinal transit with charcoal meal. Hemenway, CL; Mittelstadt, SW; Spruell, RD, )	0.13
" Dosing frequency was in accordance with prescribing information for 97."	( Retrospective analysis of Kadian (morphine sulfate sustained-release capsules) in patients with chronic, nonmalignant pain. Chao, J, )	0.41
"Comparisons of spontaneous mutant C57BL/6-Mc1r(e/e) mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants."	( Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. Bijl, H; Dahan, A; Fillingim, RB; Kaplan, L; Mogil, JS; Ritchie, J; Romberg, RR; Sarton, EY; Smith, SB; Strasburg, K; Wallace, MR, 2005)	0.53
"When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression."	( Preoperative "fentanyl challenge" as a tool to estimate postoperative opioid dosing in chronic opioid-consuming patients. Davis, JJ; Dillon, JD; Egan, TD; Hall, RH; Johnson, KB; Niu, SY; Pace, NL; Swenson, JD, 2005)	0.33
"6-fold shift in morphine's dose-response curve."	( Attenuation of morphine tolerance by intrathecal gabapentin is associated with suppression of morphine-evoked excitatory amino acid release in the rat spinal cord. Lee, MS; Lin, JA; Lin, SL; Wen, ZH; Wong, CS; Wu, CT; Yeh, CC, 2005)	1.03
" In vivo MCL-145 produced a full dose-response curve in the 55 degrees C warm water tail-flick test and was equipotent to morphine."	( Characterization of a novel bivalent morphinan possessing kappa agonist and micro agonist/antagonist properties. Bidlack, JM; Mathews, JL; Negus, SS; Neumeyer, JL; Peng, X; Xiong, W; Zhang, A, 2005)	0.54
" Antinociception dose-response curves were analyzed to obtain the ED50's of each drug."	( Analgesic synergism between intrathecal morphine and cyclooxygenase-2 inhibitors in mice. Miranda, HF; Pinardi, G; Prieto, JC, 2005)	0.6
" As a consequence, there was no significant dosing time-dependent difference in the analgesic effect of morphine in CRH-deficient mice."	( Glucocorticoid hormone regulates the circadian coordination of micro-opioid receptor expression in mouse brainstem. Fujioka, T; Higuchi, S; Koyanagi, S; Matsuo, A; Ohdo, S; To, H; Yoshida, M, 2005)	0.54
" Subjects were given intravenous morphine (4-6mg dosed by ideal body weight) and placebo in random order on separate visits, and completed serial pain ratings over three hours at each session."	( The association between negative affect and opioid analgesia in patients with discogenic low back pain. Davar, G; Jamison, R; Wasan, AD, 2005)	0.61
" In subsequent testing, dose-response curves were determined for the individual drugs, for a wide range of dose combinations of the training drugs, and for two drugs to which the pigeons had not been exposed previously (pseudoephedrine and nicotine)."	( Effects of amphetamine-CNS depressant combinations and of other CNS stimulants in four-choice drug discriminations. Li, M; McMillan, DE; Wessinger, WD, 2005)	0.33
" However, the frequency of postoperative opioid dosing can be minimized and may be a factor when contemplating supplementary use of epidural or intra-articular injections as part of a balanced analgesic approach."	( Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy. Harvey, RC; Hoelzler, MG; Lidbetter, DA; Millis, DL, )	0.13
" Further studies are required to determine whether a higher dosage of tenoxicam is beneficial to reduce uterine cramping pain in multiparous women."	( Differential analgesic effect of tenoxicam on post-cesarean uterine cramping pain between primiparous and multiparous women. Chen, SY; Lin, CJ; Sun, WZ; Yeh, HM; Yeh, YC, 2005)	0.33
" Moreover, mice receiving morphine for 8 days demonstrated a significant rightward shift of the morphine antinociceptive dose-response curve, indicative of antinociceptive tolerance, whereas those that also received amlodipine along with morphine did not demonstrate tolerance."	( Spinal L-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance. Bilsky, EJ; Dogrul, A; Lai, J; Ossipov, MH; Porreca, F, 2005)	0.63
" Increasing magnesium dosage did not offer any advantages, but induced haemodynamic consequences."	( Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Akpir, K; Kayacan, S; Pembeci, K; Seyhan, TO; Sungur, MO; Telci, L; Tugrul, M, 2006)	0.33
" Total narcotic dosage and pain scale scores were not statistically different."	( Heating and humidifying of carbon dioxide during pneumoperitoneum is not indicated: a prospective randomized trial. Barrett, MS; Davis, SS; Dundon, J; Fries, R; Goldblatt, MI; Larson, T; Melvin, WS; Mikami, DJ; Needleman, BJ; Newlin, M, 2006)	0.33
" Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia."	( Morphine reward in dopamine-deficient mice. Hnasko, TS; Palmiter, RD; Sotak, BN, 2005)	2
" Intrathecal drug delivery systems can be highly effective in a variety of patient settings, including cases of refractory pain, diminished performance status, poor tolerability of oral medications, polyanalgesia for complex pain, and inadequate dosing due to addiction concerns."	( Intrathecal drug delivery for the management of cancer pain: a multidisciplinary consensus of best clinical practices. Boortz-Marx, R; Du Pen, S; Friehs, G; Gordon, M; Halyard, M; Herbst, L; Kiser, J; Stearns, L, )	0.13
"5-5 mg/kg) produced a rightward shift of a heroin dose-response curve, while vigabatrin (75-300 mg/kg), baclofen (0."	( Role of opioidergic mechanisms and GABA uptake inhibition in the heroin-induced discriminative stimulus effects in rats. Filip, M; Krówka, T; Przewłocki, R; Solecki, W, )	0.13
" Our findings suggest that a single preoperative dose of ketamine provided less analgesia compared with other dosing regimens that included intraoperative infusions or postoperative administration."	( The influence of timing of systemic ketamine administration on postoperative morphine consumption. Alev, T; Bilgin, H; Bilgin, T; Kerimoğlu, B; Osma, S; Ozcan, B; Toker, A; Uçkunkaya, N, 2005)	0.56
" Drugs that may be useful in relieving suffering are described with dosing proposals."	( [The dying patient]. Paulsen, Ø; Rosland, JH; von Hofacker, S, 2006)	0.33
" It is important that akathisia is recognized and treated appropriately as an adverse reaction to drugs and a further increase in antipsychotic medication dosage may further exacerbate the condition."	( [Three cases of drug-induced akathisia due to antiemetics during cancer palliative care]. Horikoshi, Y; Kitade, H; Kitanaka, N; Matsu-ura, T; Mikayama, H; Miyama, S; Mori, T; Ogura, T; Ohta, Y; Okuno, M; Sawaragi, S; Takada, H; Teramura, S; Tsuji, Y; Uemura, Y; Yamada, M; Yoneda, A, 2006)	0.33
" In contrast, in the applied single dosage chronic morphine treatment did not influence either the APP and BACE protein levels or the APP mRNA production."	( 3,4-Methylenedioxymethamphetamine (MDMA), but not morphine, alters APP processing in the rat brain. Bjelik, A; Fürst, Z; Gyarmati, Z; Horváth, Z; Hugyecz, M; Janka, Z; Kálmán, J; Pákáski, M; Rakonczay, Z; Tímár, J; Zana, M, 2007)	0.84
" Mice were then given morphine in a 4-day escalating morphine administration paradigm followed by reassessment of the morphine dose-response relationship."	( Chronic pain and genetic background interact and influence opioid analgesia, tolerance, and physical dependence. Clark, DJ; Guo, T; Kingery, WS; Liang, DY; Liao, G; Peltz, G, 2006)	0.65
" In chronic studies, the morphine dosing regimen was adjusted in each strain/sex to produce comparable levels of tolerance."	( Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. Barrett, AC; Lomas, LM; Negus, SS; Picker, MJ; Terner, JM, 2006)	0.9
" In Group MNG, the dose-response curve shifted back to the right and the ED50 for inducing paraparesis was 11."	( Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat. Fuchigami, T; Kakinohana, M; Murata, K; Nakamura, S; Sugahara, K, 2006)	0.6
" Dose-response curves were generated for each test drug."	( Development of tolerance and sensitization to different opioid agonists in rats. Bartzsch, K; Becker, A; Grecksch, G; Höllt, V; Koch, T; Widera, A, 2006)	0.33
" These results indicate that the endogenous OFQ/N system is differentially involved in morphine tolerance development and establishment of opiate dependence, depending on the specific morphine dosage regimen."	( Endogenous orphanin FQ/nociceptin is involved in the development of morphine tolerance. Chung, S; Civelli, O; Pohl, S; Reinscheid, RK; Zeng, J, 2006)	0.79
" This paper summarizes the current evidence for opioid dosing in newborns, reviews their side-effects and explains the use of population kinetics and non-linear mixed-effects modeling to analyze the data from clinical trials."	( Pain control: opioid dosing, population kinetics and side-effects. Anand, KJ; Simons, SH, 2006)	0.33
" l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower."	( Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat. Kalso, E; Kontinen, VK; Kylänlahti, I; Lemberg, K; Viljakka, K; Yli-Kauhaluoma, J, 2006)	1.98
" Patient-controlled analgesia was used for the first 3 postoperative days in all patients, and the cumulative dosage used was recorded."	( Analgesic effect of electroacupuncture in postthoracotomy pain: a prospective randomized trial. Chan, SK; Lee, TW; Liang, YM; Ng, CS; Sihoe, AD; Wan, IY; Wong, RH; Wong, WW; Yim, AP, 2006)	0.33
" Acute administration of lithium, in a dose of 3 mmol/kg, 30 min prior to morphine dosing did not influence morphine-induced analgesia compared to all the clock-time test-matched morphine groups, except the 9 HALO (Hours After Lights On) one."	( Temporal variation in drug interaction between lithium and morphine-induced analgesia. Bora, N; Demirel, O; Karakucuk, EH; Yamanoglu, T; Zengil, H, 2006)	0.81
" For pain patients who have reduced renal function such as those in palliative care, most opioids used for chronic pain treatment should be administered at reduced dosages, with increased dosage intervals, or not at all because of the risk of accumulation of the parent compound or its metabolites."	( Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Böger, RH, 2006)	0.33
" Moreover, dose-response curves of the agonists showed that mu and CB1 receptors mediating inhibition of [3H]glutamate release display a non-additive interaction, whereas these receptors synergistically interact regarding their inhibitory control of [3H]GABA release."	( Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. De Vries, TJ; Hogenboom, F; Schoffelmeer, AN; Wardeh, G, 2006)	0.33
" Two dose-response functions (0."	( Effects of morphine on circadian rhythms of motor activity and body temperature in pig-tailed macaques. Hienz, RD; Weed, MR, 2006)	0.72
"Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24-week treatment period."	( Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Nicholson, B; Ross, E; Sasaki, J; Weil, A, 2006)	0.58
" After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID)."	( Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Nicholson, B; Ross, E; Sasaki, J; Weil, A, 2006)	0.58
"P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID)."	( Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Nicholson, B; Ross, E; Sasaki, J; Weil, A, 2006)	0.58
" In the future, identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control."	( Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Chou, WY; Jawan, B; Liu, CC; Liu, PH; Tseng, CC; Wang, CH, 2006)	0.55
" The median daily dose to achieve this was 15 mg (range: 5-30 mg) and the median time to first bowel movement after dosing was 11."	( Sodium picosulfate in opioid-induced constipation: results of an open-label, prospective, dose-ranging study. Jordan, C; Kamm, MA; McNamara, P; Schuijt, C; Twycross, RG, 2006)	0.33
"Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain in cancer patients."	( Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. Aielli, F; Casuccio, A; Ferrera, P; Mercadante, S; Porzio, G; Verna, L; Villari, P, 2006)	0.6
" The present study was undertaken to determine: 1) whether different parenteral opioids are dosed equivalently; 2) which patient factors affect equianalgesic dose; and 3) which patient factors affect opioid choice."	( Underdosing of morphine in comparison with other parenteral opioids in an acute hospital: a quality of care challenge. Lang, VJ; O'Connor, AB; Quill, TE, )	0.48
" Inadequate bolus dosing of morphine may be a barrier to appropriate patient analgesia."	( Underdosing of morphine in comparison with other parenteral opioids in an acute hospital: a quality of care challenge. Lang, VJ; O'Connor, AB; Quill, TE, )	0.78
" The data were analysed for three dosage groups (<0."	( Morphine-related apnoea in CPAP-treated preterm neonates. Enders, J; Gebauer, C; Knüpfer, M; Pulzer, F; Robel-Tillig, E, 2006)	1.78
" Morphine in a low dosage (	( Morphine-related apnoea in CPAP-treated preterm neonates. Enders, J; Gebauer, C; Knüpfer, M; Pulzer, F; Robel-Tillig, E, 2006)	2.69
" Strategies to change physician attitudes and beliefs regarding morphine in CPM should focus on tolerance concepts, dosing schemes, safety, efficacy, lack of addictive risk, use of drug combinations, and the fact that cancer pain can be relieved."	( Physician attitudes and beliefs about use of morphine for cancer pain. Elliott, BA; Elliott, TE, 1992)	0.78
" The objective of this manuscript is to develop a cumulative dose microinjection procedure so the hypothesized role of the PAG in morphine antinociceptive tolerance can be assessed using dose-response analysis."	( Antinociceptive tolerance revealed by cumulative intracranial microinjections of morphine into the periaqueductal gray in the rat. Fossum, EN; Ingram, SL; Levine, CS; Morgan, MM, 2006)	0.76
" Therefore, opiate dosing in children with OSA must take into account a history of recurrent hypoxemia."	( Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Brown, KA; Laferrière, A; Lakheeram, I; Moss, IR, 2006)	0.33
" Total codeine dosage was also similar, except at 4 h postoperatively when it was higher in the block group."	( A comparison between scalp nerve block and morphine for transitional analgesia after remifentanil-based anesthesia in neurosurgery. Ayoub, C; Boudreault, D; Chouinard, P; Girard, F; Moumdjian, R; Ruel, M, 2006)	0.6
"Little information is available about the incidence, prevalence, or severity of morphine side effects during repeated individualized dosing for chronic cancer pain, although it has been widely used in this way for more than 30 years."	( The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain. Glare, P; Sheehan, D; Walsh, D, )	0.67
" In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen."	( Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol. Dursteler, C; Miranda, HF; Pinardi, G; Prieto, JC; Puig, MM, 2007)	0.56
" In the presence of fixed doses of 1 or 10 microg CTAP, increasing doses of naltrexone produced dose-dependent shifts to the right in the morphine dose-response curve."	( In vivo pharmacological resultant analysis reveals noncompetitive interactions between opioid antagonists in the rat tail-withdrawal assay. Walker, EA, 2006)	0.54
" METH1 evoked a transient threefold increase in DA overflow in only one-third of dosed rats."	( Methamphetamine, morphine, and their combination: acute changes in striatal dopaminergic transmission evaluated by microdialysis in awake rats. Ali, SF; Lourenço, E; Macedo, TR; Milhazes, N; Morgadinho, T; Pereira, FC; Ribeiro, CF, 2006)	0.67
" Early efficacy data suggest that DepoCyt is fairly well tolerated, and its use allows reduced dosing frequency from twice a week to once every other week and may improve the outcome compared with frequent intrathecal injections of unencapsulated cytarabine."	( Pharmacology of drugs formulated with DepoFoam: a sustained release drug delivery system for parenteral administration using multivesicular liposome technology. Angst, MS; Drover, DR, 2006)	0.33
" Ablation of NK-1 receptor expressing cells prevented (a) morphine-induced thermal and mechanical hypersensitivity, (b) increased touch-evoked spinal FOS expression, (c) upregulation of spinal dynorphin content and (d) the rightward displacement of the spinal morphine antinociceptive dose-response curve (i."	( Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. King, T; Lai, J; Ossipov, MH; Porreca, F; Vanderah, TW; Vera-Portocarrero, LP; Zhang, ET, 2007)	0.58
" As previously reported, when a within-subjects design and cumulative dosing was employed, no tolerance was observed in the 129P3/J strain."	( Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice. Bryant, CD; Byun, JS; Evans, CJ; Fanselow, MS; Roberts, KW, 2006)	1.78
" The MQS score accounted for variations in the types of analgesic medications, routes of administration, dosing schedules, and opioid dosing requirements."	( Quantification of analgesic use in children with sickle cell disease. Beyer, JE; Jacob, E; Miaskowski, C; Savedra, M; Styles, L; Treadwell, M, 2007)	0.34
" Presently, the dose-response characteristics between maternal cocaine use and fetal exposure and adverse effects are unknown."	( Cocaine detection in maternal and neonatal hair: implications to fetal toxicology. Garcia-Bournissen, F; Karaskov, T; Koren, G; Rokach, B, 2007)	0.34
" Thus, dextro-morphine pretreatment induces a U-shaped dose-response curve for attenuating the morphine-produced conditioned place preference."	( dextro-Morphine attenuates the morphine-produced conditioned place preference via the sigma(1) receptor activation in the rat. Schwasinger, ET; Terashvili, M; Tseng, LF; Wu, HE, 2007)	1.16
"3-fold leftward shift of morphine's dose-response curve in morphine-tolerant rats, and this was associated with GLAST and GLT-1 trafficking onto the cell surface."	( Amitriptyline preserves morphine's antinociceptive effect by regulating the glutamate transporter GLAST and GLT-1 trafficking and excitatory amino acids concentration in morphine-tolerant rats. Liu, TM; Tai, YH; Tao, PL; Tsai, RY; Wang, JJ; Wang, YC; Wang, YH; Wong, CS, 2007)	0.95
" The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine."	( Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of mu-opioid receptors and dynamin-2. Kumar, P; Pawar, M; Sirohi, S; Sunkaraneni, S; Walker, EA; Yoburn, BC, 2007)	0.58
" We hold that current evidence supports the administration of opioids to children with acute abdominal pain, and future trials will help determine safe and effective timing and dosing related to opioid administration."	( Opioid administration for acute abdominal pain in the pediatric emergency department. Goldman, RD; Klein-Kremer, A, )	0.13
" In addition to standard solution analysis, this approach was successfully applied for quantitative determination of morphine in a typical pharmaceutical dosage form."	( Kinetic determination of morphine by means of Bray-Liebhafsky oscillatory reaction system using analyte pulse perturbation technique. Anić, SR; Blagojević, SM; Cirić, JS; Kolar-Anić, LZ; Marković, SD; Marković, ZS; Mijatović, MD; Pejić, ND; Vukojević, VB, 2007)	0.85
" For caffeine and scopolamine, even the lowest dosage tested (5 mg/horse/day and 2 mg/horse/day respectively) induced detectable concentrations of the molecule in urine."	( Urinary excretion of dietary contaminants in horses. Bonnaire, Y; Julliand, V; Lallemand, A; Respondek, F, 2006)	0.33
" Information on the pharmacokinetics of ketorolac in infants is sparse, making dosing difficult."	( Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anderson, GD; Bradford, H; Chen, J; Ellenbogen, RG; Kantor, ED; Lynn, AM; Salinger, DH; Seng, KY; Vicini, P, 2007)	0.56
" Dosing simulations, using population pharmacokinetic parameters, showed no accumulation of S(-) ketorolac but steady increases in R(+) ketorolac."	( Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anderson, GD; Bradford, H; Chen, J; Ellenbogen, RG; Kantor, ED; Lynn, AM; Salinger, DH; Seng, KY; Vicini, P, 2007)	0.56
" During this period, the side effects, the dosage of rescue analgesia required, and the range of knee flexion were recorded for each group."	( Intra-synovial ropivacaine and morphine for pain relief after total knee arthroplasty: a prospective, randomized, double blind study. Han, CD; Lee, DH; Yang, IH, 2007)	0.63
" Morphine dose-response relationships were established both prior to and after chronic morphine treatment."	( The beta2 adrenergic receptor regulates morphine tolerance and physical dependence. Clark, JD; Li, J; Li, X; Liang, DY; Shi, X, 2007)	1.52
" Both morphine and lidocaine retained topical activity following chronic sciatic nerve injury, but their analgesic dose-response curves were shifted to the right when compared to sham-operated mice."	( Reorganization of dorsal root ganglion neurons following chronic sciatic nerve constriction injury: correlation with morphine and lidocaine analgesia. El-Maarouf Abderrahman, A; El-Maarouf, A; Kolesnikov, Y; Pasternak, G; Rutinhauser, U; Rutishauser, U, 2007)	1.03
"Among 68 men and 30 women, dosage of epidural morphine was not significantly different by gender."	( [Sexual differences in effects and side effects of epidural morphine for VATS (video-associated thoracic surgery)]. Kawagoe, I; Sumida, T, 2007)	0.84
" A leftward shift in the dose-response curve was observed following WIN55,212-2 relative to morphine treatment."	( Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. Hohmann, AG; Makriyannis, A; Rahn, EJ, 2007)	0.56
" Linear regression analysis showed that morphine dosage and duration were significantly associated with the duration of mechanical ventilation."	( Safety profile of morphine following surgery in neonates. De Silva, N; El Sayed, MF; Fallah, S; Moore, AM; Taddio, A, 2007)	0.94
"Thirty-six randomized, double-blind controlled clinical trials with 49 comparisons, including multiple dosage regimens and routes of administration were included."	( A qualitative systematic review of morphine treatment in children with postoperative pain. Duedahl, TH; Hansen, EH, 2007)	0.62
" No relation between morphine dosage and analgesic efficacy was detected."	( A qualitative systematic review of morphine treatment in children with postoperative pain. Duedahl, TH; Hansen, EH, 2007)	0.94
" Mean VAS was 16 mm for morning dosing and 14 mm for evening dosing (P=0."	( A randomized, double-blind, multi-site, crossover, placebo-controlled equivalence study of morning versus evening once-daily sustained-release morphine sulfate in people with pain from advanced cancer. Cooney, NJ; Currow, DC; Glare, PA; Gorman, D; Plummer, JL, 2007)	0.54
" Furthermore, adequate dosing remains a problem since no objective measurement of pain severity exists and analgesia should be titrated upon the patient's reported pain."	( Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. Biemond, BJ; Friederich, PW; Nieuwkerk, PT; van Beers, EJ; van Tuijn, CF; Vranken, JH, 2007)	0.58
" The average wholesale price per dosing unit of each drug during each period studied was obtained from internal databases."	( Prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital. Arbuckle, R; Bruera, E; Curry, EA; Hung, F; Palla, S, 2007)	0.34
" SPILA granules were orally administered to beagle dogs to compare the pharmacokinetics with commercially available twice-a-day dosage form, MS Contin."	( Pharmacokinetic and pharmacodynamic evaluations of novel oral morphine sustained release granules. Akiyama, Y; Fuse, T; Nakamura, K; Nara, E, 2007)	0.58
"Lacking enough knowledge of pediatric cancer pain and pediatric dosage form of analgesics, current treatment of pediatric cancer pain in China is unsatisfactory."	( [Feasibility to treat pediatric cancer pain with analgesics for adults and their efficacy]. Lin, H; Ling, JY; Luo, WB; Sun, XF; Xia, Y; Zhen, ZJ; Zheng, L, 2007)	0.34
"Basing on the components and the endurable dosage of each component for children, we formulated the appropriate dosage and usage of a few analgesics (including sustained release tablets of morphine, oxycodone and transdermal fantanyl) available in China, most of which were used in adults."	( [Feasibility to treat pediatric cancer pain with analgesics for adults and their efficacy]. Lin, H; Ling, JY; Luo, WB; Sun, XF; Xia, Y; Zhen, ZJ; Zheng, L, 2007)	0.53
"2-20 mg/kg/day), and spinal micro-opioid receptor density was examined, or morphine analgesia dose-response studies were conducted."	( Mu-opioid receptor up-regulation and functional supersensitivity are independent of antagonist efficacy. Kumar, P; Sirohi, S; Yoburn, BC, 2007)	0.57
" The dose-response curves of butorphanol were studied using selective MOR and KOR antagonists."	( Effects of butorphanol on morphine-induced itch and analgesia in primates. Ko, MC; Lee, H; Naughton, NN; Woods, JH, 2007)	0.64
" Out-of-hospital pain management using morphine depends on careful attention to dosage and the time interval between re-injections."	( Compliance with a morphine protocol and effect on pain relief in out-of-hospital patients. Adnet, F; Belpomme, V; Borron, S; Chollet, C; Devaud, ML; Mantz, J; Marty, J; Ricard-Hibon, A, 2008)	0.95
" Modified release versions of morphine were effective for 12 or 24-hour dosing depending on the formulation."	( Oral morphine for cancer pain. McQuay, HJ; Wiffen, PJ, 2007)	1.14
" Pain intensity, relative dosing ratios, discontinuation rates, and adverse events were assessed."	( The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies. Damaraju, CV; Hewitt, DJ; Kershaw, P; Siccardi, M; Viscusi, ER, 2007)	0.56
" The aim of this study was to target patients who had painful mucositis at grade III-IV and treat their radiation-induced mucositis with gastrostomy administered morphine in an extended-release dosing form."	( Administration of morphine sulfate extended-release capsules via gastrostomy: dissolution study and case reports. Anderson, K; Ghalie, R; Homel, P; Loewen, G; Mori, M; Portenoy, R; Shaiova, L, 2007)	0.87
" Opioid dosing intervals and supplemental opioid doses were most often adequate."	( Pain management of opioid-treated cancer patients in hospital settings in Denmark. Lundorff, L; Peuckmann, V; Sjøgren, P, 2008)	0.35
" However, fentanyl concentration decreases quite rapidly and patients may need repeated dosing until analgesia is attained."	( [Postoperative analgesia after remifentanil]. Kiyama, S, 2007)	0.34
" The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting."	( Mechanisms of morphine enhancement of spontaneous seizure activity. Brull, R; Carlen, PL; Derchansky, M; El Beheiry, H; Ismaili, M; Jahromi, SS; Saboory, E, 2007)	0.96
" Dose-response and time course curves were done."	( Role of nociceptin/orphanin FQ and the pseudopeptide [Phe1Psi(CH2NH)Gly2]-nociceptin(1-13)-NH2 and their interaction with classic opioids in the modulation of thermonociception in the land snail Helix aspersa. Cruz, SL; León-Olea, M; Miller-Pérez, C; Pellicer, F; Rodríguez-Manzo, G; Sánchez-Islas, E, 2008)	0.35
" Demerol requires a higher dosage than methadone, but produces less respiratory depression."	( A comparison of certain actions of demerol and methadone. BUCHANAN, OH; TAINTER, ML, 1949)	0.23
"The aim of this study was to explore the potential association between a dose-response effect of morphine exposure and the development of ACS in children with SCD who presented with VOC."	( Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study. Blanchette, V; Finkelstein, Y; Garcia-Bournissen, F; Juurlink, DN; Kirby, M; Koren, G; Nurmohamed, L; Schechter, T, 2007)	1.18
"Among these children with SCD who presented with VOC, the administration of morphine was not found to be associated with a dose-response effect on the risk for ACS."	( Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study. Blanchette, V; Finkelstein, Y; Garcia-Bournissen, F; Juurlink, DN; Kirby, M; Koren, G; Nurmohamed, L; Schechter, T, 2007)	1.19
" Analysis of variance ratios of least-squares means for ln-transformed AUC(infinity) and C(max) satisfied the criteria (90% confidence intervals within 80%-125%) to declare no drug formulation interaction among the KADIAN regimens dosed with alcohol compared with KADIAN taken with water."	( Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules. Johnson, F; Stauffer, J; Sun, S; Wagner, G, 2008)	0.57
" For the acute morphine studies, antinociceptive responses were assessed using cumulative morphine dosing (0."	( Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats. Holtzman, SG; Michaels, CC; White, DA, 2008)	0.92
" However, few studies are so far available on how increases in daily opioid dosage affect driving ability."	( [Influence of changes to daily dose of opioids on aspects of cognitive and psychomotor performance involved in driving]. Berghaus, G; Dagtekin, O; Elsner, F; Gaertner, J; Gerbershagen, HJ; Kolibay, F; Radbruch, L; Sabatowski, R; Theisohn, M, 2008)	0.35
"74 times higher dosage than non-cancer pain patients (6110."	( [Trend in opioids use for chronic pain treatment at Clalit Health Services (2000-2004)]. Brill, S; Freud, T; Sherf, M; Shvartzman, P; Singer, Y; Vardy, D, 2007)	0.34
" The primary outcome was a dose-response assessment for total pain relief based upon visual analog scales."	( Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Carr, DB; Ernst, C; Gawarecki, D; Hamilton, D; McNicol, E; Mermelstein, F; Reber, KR; Stoker, DG; Waltzman, LS; Wright, C, )	0.41
"5 mg and 15 mg dosage groups, respectively, and 130 minutes for IV morphine."	( Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Carr, DB; Ernst, C; Gawarecki, D; Hamilton, D; McNicol, E; Mermelstein, F; Reber, KR; Stoker, DG; Waltzman, LS; Wright, C, )	0.65
" The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49."	( Neonatal morphine enhances nociception and decreases analgesia in young rats. Sweitzer, SM; Zhang, GH, 2008)	1.11
"Morphine and buprenorphine had parallel dose-response curves in blocking FPS, with buprenorphine 40 times more potent than morphine."	( Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone. Davis, M; Glover, EM, 2008)	2.09
" In cases of minimal or absent spontaneous breathing the disconnection was realized in deep sedation, which required a moderate total dose of morphine sulfate (120 mg) but a high dosage rate (up to 300 mg/h)."	( [Elective termination of respiratory therapy in amyotrophic lateral sclerosis]. Borisow, N; Dullinger, JS; Hempel, E; Keil, JP; Linke, P; Meyer, T; Münch, C; Rosseau, S, 2008)	0.55
" A similar rightward shift in the morphine dose-response curve was caused by morphine tolerance."	( Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal gray modulates morphine antinociception. Fossum, EN; Ingram, SL; Lisowski, MJ; Macey, TA; Morgan, MM, 2008)	0.84
"Intrathecal morphine dosing remained constant during the titration phase."	( Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. Fisher, R; Kosek, PS; Leong, M; Schultz, DM; Staats, P; Wallace, MS, 2008)	0.96
"Multicenter, open-label study with a 4-week morphine titration phase during which ziconotide was held constant and an extension phase during which dosing of either drug could vary."	( Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain. Charapata, S; Fakata, KL; Fisher, R; MineHart, M; Webster, LR, 2008)	0.86
"Ziconotide dosing remained constant during the titration phase; intrathecal morphine titration was based on each patient's daily systemic opioid dose at the study's start."	( Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain. Charapata, S; Fakata, KL; Fisher, R; MineHart, M; Webster, LR, 2008)	0.82
"5-fold right-shift in the morphine dose-response curve compared with a 65-fold right-shift in its absence) and this effect was inhibited by Ro106-9920 administration (48-fold right-shift)."	( Amitriptyline induces nuclear transcription factor-kappaB-dependent glutamate transporter upregulation in chronic morphine-infused rats. Cherng, CH; Liu, TM; Tai, YH; Tao, PL; Tsai, RY; Wang, YH; Wong, CS, 2008)	0.86
" When dosed correctly, a life-shortening effect can be definitely excluded today."	( [Does morphine have a life-shortening effect?]. Baust, G, 2008)	0.83
" Thus, like given systemically, (+)-morphine given into the posterior nucleus accumbens shell also induces a U-shaped dose-response curve for attenuating the (-)-morphine-produced conditioned place preference."	( (+)-Morphine attenuates the (-)-morphine-produced conditioned place preference and the mu-opioid receptor-mediated dopamine increase in the posterior nucleus accumbens of the rat. Hong, JS; Hung, KC; Schwasinger, ET; Terashvili, M; Tseng, LF; Wu, HE, 2008)	1.18
" The survey showed a wide variation in morphine and paracetamol dosing and the absence of a paracetamol loading dose in a fourth of the units."	( Pain management in Swedish neonatal units--a national survey. Eriksson, M; Gradin, M, 2008)	0.62
"Morphine in dosage less than half of recommended dosage has a high analgetic and sedative potential."	( Analgosedation with low-dose morphine for preterm infants with CPAP: risks and benefits. Enders, J; Gebauer, C; Knüpfer, M; Pulzer, F; Robel-Tillig, E, 2008)	2.08
"Ketamine decreases postoperative morphine consumption, but its optimal dosing and duration of administration remain unclear."	( Postoperative ketamine administration decreases morphine consumption in major abdominal surgery: a prospective, randomized, double-blind, controlled study. Beloucif, S; Dupont, H; Lorne, E; Montravers, P; Moubarak, M; Samarcq, D; Zakine, J, 2008)	0.88
" The increased responding observed in the MW group compared with the control and MD groups resulted in an upward shift in the remifentanil dose-response curve, an effect that was expressed only after repeated exposure to the contingency, demonstrating that morphine withdrawal ultimately enhances the reinforcing effects of remifentanil."	( Morphine deprivation increases self-administration of the fast- and short-acting mu-opioid receptor agonist remifentanil in the rat. Cooper, ZD; Shi, YG; Truong, YN; Woods, JH, 2008)	1.97
" Morphine sulfate extended-release capsules, the only opioid formulation indicated in the US for both once- and twice-daily (every 12 and every 24 h) dosing, is approved in eight dosage strengths and is effective against pain from diverse sources in a variety of patient types."	( Morphine sulfate extended-release capsules for the treatment of chronic, moderate-to-severe pain. Nicholson, B, 2008)	2.7
" Nearly all patients taking morphine sulfate extended-release capsules for pain relief adhere to the recommended dosing frequency."	( Morphine sulfate extended-release capsules for the treatment of chronic, moderate-to-severe pain. Nicholson, B, 2008)	2.08
" Immediately after surgery, there was less pain, higher satisfaction, and lower morphine use among patients on continuous FNB regardless of ropivacaine dosage used."	( Continuous femoral nerve block in total knee arthroplasty: immediate and two-year outcomes. Chong, HC; Lo, NN; Shum, CF; Yang, KY; Yeo, SJ; Yeo, SN, 2009)	0.58
"6 mg/kg) and 24 h later fentanyl cumulative dose-response studies were conducted."	( The analgesic efficacy of fentanyl: relationship to tolerance and mu-opioid receptor regulation. Dighe, SV; Sirohi, S; Walker, EA; Yoburn, BC, 2008)	0.35
" Interestingly, neonatally injured animals that did not receive morphine displayed a significant rightward shift in the morphine dose-response curve in the absence of peripheral inflammation."	( Preemptive morphine analgesia attenuates the long-term consequences of neonatal inflammation in male and female rats. Johns, ME; Laprairie, JL; Murphy, AZ, 2008)	0.97
" Repeated injections of morphine caused a rightward shift in the morphine dose-response curve on Day 3 (i."	( Repeated cannabinoid injections into the rat periaqueductal gray enhance subsequent morphine antinociception. Maher, L; Morgan, MM; Wilson, AR, 2008)	0.88
"Identify the dosing regimen of intrathecal morphine that safely and effectively provides postoperative analgesia with minimal complications in patients with idiopathic scoliosis undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI)."	( Intrathecal morphine for postoperative analgesia in patients with idiopathic scoliosis undergoing posterior spinal fusion. Poe-Kochert, C; Potzman, J; Son-Hing, JP; Thompson, GH; Tripi, PA, 2008)	0.99
"A physical morphine dependent model of rats was established by subcutaneous injection of morphine in gradually increasing dosage within 7 days."	( [Effect of cedemex on cAMP and cGMP levels of different brain areas in morphine withdrawal rats]. Chen, TP; Fan, JM; Guo, SC; Huang, JC; Huang, RB; Jiang, WZ; Lai, S; Liang, YG; Nguyen, PK; Xie, HY, 2008)	0.97
" Many exhibit methodologic problems with dosing regimes or study design."	( Therapeutic effect of intrathecal morphine after posterior lumbar interbody fusion surgery: a prospective, double-blind, randomized study. Bauer, C; Fritsch, E; Mencke, T; Müller, BI; Silomon, M; Soltesz, S; Ziegeler, S, 2008)	0.63
" Dose-response relationships were determined for nonsedating doses of both drugs given alone and together in combination in causing antinociception in two nociception paradigms: carrageenan paw inflammation and streptozotocin-induced diabetic neuropathy."	( Combination therapy with flupirtine and opioid: studies in rat pain models. Cooke, I; Goodchild, CS; Kolosov, A; Tucker, AP, 2008)	0.35
" While its efficacy has been well documented in randomized controlled trials, the safety and clinically appropriate dosing are less well defined."	( Extended-release epidural morphine (DepoDur): review and safety analysis. Hartrick, CT; Hartrick, KA, 2008)	0.65
" In mice without inflammation, subplantar opioids did not induce antinociception, while during CFA-inflammation, all drugs generated dose-response curves with an order of potency of: U-50488H < DPDPE < morphine < buprenorphine < fentanyl << CRF."	( Tolerance to the antinociceptive effects of peripherally administered opioids. Expression of beta-arrestins. Almela, P; García-Nogales, P; Hernández, L; Laorden, ML; Puig, MM; Romero, A, 2009)	0.54
"Forty-five opium-dependent Thai subjects were allocated to three dosing groups (6."	( Flexible dosing of tincture of opium in the management of opioid withdrawal: pharmacokinetics and pharmacodynamics. Abadi, RM; Ali, R; Jittiwutikarn, J; Larsen, M; Somogyi, AA; White, JM, 2008)	0.35
"The management of opioid withdrawal can be achieved, with minimal adverse effects, by using flexible dosing of TOP."	( Flexible dosing of tincture of opium in the management of opioid withdrawal: pharmacokinetics and pharmacodynamics. Abadi, RM; Ali, R; Jittiwutikarn, J; Larsen, M; Somogyi, AA; White, JM, 2008)	0.35
" Opiate dosage consumed was also recorded as a primary outcome during the first 24 h following surgery."	( Post-operative pain relief following intrathecal injection of acetylcholine esterase inhibitor during lumbar disc surgery: a prospective double blind randomized study. Hamidi, S; Khan, ZH; Majedi, H; Miri, M; Nourijelyani, K, 2008)	0.35
" Quantification of benefit and harm and assessment of dose-response are needed."	( Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials. Elia, N; Lysakowski, C; Meylan, N; Tramèr, MR, 2009)	0.64
" The systems studied in this work are kollidon SR microparticles, a biodegradable polymer classically used as excipient in the design of solid dosage forms, as vehicles for morphine."	( Kollidon SR colloidal particles as vehicles for oral morphine delivery in pain treatment. Arias, JL; Delgado, AV; Gómez-Gallo, A; Ruiz, MA, 2009)	0.8
" Dosing regimens varied widely."	( Management of neonatal abstinence syndrome: a national survey and review of practice. Hopewell, J; O'Grady, MJ; White, MJ, 2009)	0.35
" Following treatment, morphine cumulative dose-response studies were conducted (tail flick)."	( Continuous morphine produces more tolerance than intermittent or acute treatment. Dighe, SV; Madia, PA; Sirohi, S; Yoburn, BC, 2009)	1.06
" In this series of experiments, we have evaluated the prokinetic activity of novel, small-molecule ghrelin receptor (GhrR) agonists after parenteral and peroral dosing in mice and rats."	( Enhanced gastrointestinal motility with orally active ghrelin receptor agonists. Charoenthongtrakul, S; DiStefano, PS; Flynn, N; Gagne, S; Geddes, BJ; Giuliana, D; Gordon, DA; Govek, EK; Hernández, AS; Hixon, J; Li, J; Longo, KA; Morgan, K; Murphy, BJ; Nolan, A; Tino, JA, 2009)	0.35
" The use of such mechanistic approaches improves understanding of paediatric pharmacokinetics; improving dosing predictions and allowing projection in exploratory drug development."	( Mechanistic basis of using body size and maturation to predict clearance in humans. Anderson, BJ; Holford, NH, 2009)	0.35
" The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate-release oral morphine studies."	( Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs. Aragon, CL; Barnhart, MD; Gaynor, JS; Papich, MG; Read, MR; Wilson, D, 2009)	0.92
" To clarify contradictory findings, we simultaneously determined dose-response functions of the standard 5-HT(1A)-R-agonist 8-OH-DPAT and two different opioids for spontaneous ventilation and nociception."	( The counteraction of opioid-induced ventilatory depression by the serotonin 1A-agonist 8-OH-DPAT does not antagonize antinociception in rats in situ and in vivo. Dutschmann, M; Guenther, U; Hoeft, A; Manzke, T; Putensen, C; Wrigge, H; Zinserling, J, 2009)	0.35
"(A) A dose-response relationship of 8-OH-DPAT, spontaneous phrenic nerve activity and a nociceptive C-fiber reflex (CFR) were established simultaneously in an in situ perfused, nonanesthetized, rat brainstem-spinal cord preparation."	( The counteraction of opioid-induced ventilatory depression by the serotonin 1A-agonist 8-OH-DPAT does not antagonize antinociception in rats in situ and in vivo. Dutschmann, M; Guenther, U; Hoeft, A; Manzke, T; Putensen, C; Wrigge, H; Zinserling, J, 2009)	0.35
" Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM."	( Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules. Nicholson, B; Sasaki, J; Weil, AJ, )	0.4
"8-fold right-shift of the morphine dose-response curve compared to a 77."	( Amitriptyline suppresses neuroinflammation-dependent interleukin-10-p38 mitogen-activated protein kinase-heme oxygenase-1 signaling pathway in chronic morphine-infused rats. Lin, SL; Tai, YH; Tao, PL; Tsai, RY; Wang, JJ; Wong, CS; Yeh, CC, 2009)	0.85
"Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen."	( Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study. Cubero, DI; del Giglio, A, 2010)	1
") enhanced the ascending (3 mgxkg(-1)) and descending (30 mgxkg(-1)) portions of buprenorphine's dose-response curve, but only spinal, not supraspinal, nociceptin (10 nmolxL(-1)) enhanced buprenorphine anti-nociception."	( Identification of an additional supraspinal component to the analgesic mechanism of action of buprenorphine. Ding, Z; Raffa, RB, 2009)	0.35
" However, ovariectomized mice showed decreased CPP compared to gonadally intact mice with a right shift in their morphine dose-response curve."	( Estrogen pretreatment modulates morphine-induced conditioned place preference in ovariectomized mice. Dehpour, AR; Mirbaha, H; Shaterian-Mohammadi, H; Tabaeizadeh, M; Tahsili-Fahadan, P, 2009)	0.85
" In the second experiment, using the same dosing regimen, sampling continued 3 h after morphine or saline in AV411- or vehicle-treated rats."	( The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release. Bland, ST; Hutchinson, MR; Johnson, KW; Maier, SF; Watkins, LR, 2009)	0.84
" Accordingly, there is growing interest in new approaches that would maintain opiate efficacy during repetitive dosing without engendering tolerance or unacceptable side-effects."	( Targeting peroxynitrite driven nitroxidative stress with synzymes: A novel therapeutic approach in chronic pain management. Neumann, W; Salvemini, D, 2010)	0.36
"IN ketorolac was well tolerated and effective in treating moderate-to-severe postoperative pain in inpatients; the convenience of IN dosing suggests that its usefulness in the ambulatory care setting should be evaluated."	( Intranasal ketorolac for postoperative pain: a phase 3, double-blind, randomized study. Bisley, E; Brown, C; Bynum, L; Moodie, J, 2009)	0.35
" In order to derive rational dosing schemes, the influence of aging on glucuronidation capacity in newborns, including preterms, infants and children under the age of 3 years was studied using morphine and its major metabolites as a model drug."	( Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Danhof, M; DeJongh, J; Jacqz-Aigrain, EM; Knibbe, CA; Krekels, EH; Santen, GW; Simons, SH; Tibboel, D; van den Anker, JN; van Dijk, M; van Lingen, RA, 2009)	1.99
" Future pharmacodynamic investigations are needed to reveal target concentrations in this population, after which final dosing recommendations can be made."	( Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Danhof, M; DeJongh, J; Jacqz-Aigrain, EM; Knibbe, CA; Krekels, EH; Santen, GW; Simons, SH; Tibboel, D; van den Anker, JN; van Dijk, M; van Lingen, RA, 2009)	1.8
" However, co-administration of these antagonists with morphine into the vPAG enhanced the acute antinociceptive effects of morphine as measured by a leftward shift in the morphine dose-response curves."	( Glutamate modulation of antinociception, but not tolerance, produced by morphine microinjection into the periaqueductal gray of the rat. Bobeck, EN; Ingram, SL; Morgan, MM, 2009)	0.83
" Diagnosis is based on a steady increase in intrathecal morphine dosage after a relatively prolonged period of stability, on the gradual development of neurologic signs and symptoms suggesting radicular or spinal cord compression, and on magnetic resonance images."	( [Spinal granuloma in a patient receiving a spinal infusion of morphine and clonidine]. Abejón, D; del Pozo, C; del Saz, JM; Ley, L; Sánchez, MR, )	0.62
"In an open-label study, patients with advanced cancer pain were randomized to receive SR1 or SR2 every 12 hours around-the-clock (ATC) for 5 days, with immediate release (IR) liquid morphine for rescue dosing (RD)."	( A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer. Bast, J; Homsi, J; Lasheen, W; LeGrand, SB; Nelson, KA; Rybicki, LA; Walsh, D, 2010)	0.82
"05), RD dosage (P = ."	( A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer. Bast, J; Homsi, J; Lasheen, W; LeGrand, SB; Nelson, KA; Rybicki, LA; Walsh, D, 2010)	0.62
" Mean maximum plasma morphine concentration (C(max)) after SC dosing was 29% greater with rHuPH20 than without rHuPH20 (P=0."	( The INFUSE-Morphine IIB study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneous morphine in healthy volunteers. Flament, J; Haller, MF; Thomas, JR; Yocum, RC, 2009)	1.06
" Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated."	( Poppy seed foods and opiate drug testing--where are we today? Lachenmeier, DW; Musshoff, F; Sproll, C, 2010)	0.58
" The observations from this case series lend support to the practice of maintaining stable buprenorphine dosing for patients who require major surgery."	( Effectiveness of full agonist opioids in patients stabilized on buprenorphine undergoing major surgery: a case series. Kornfeld, H; Manfredi, L, )	0.13
" Blood samples were withdrawn up to 12 h after dosing and plasma morphine concentrations were determined by HPLC with electrochemical detection."	( In vivo evaluation of a new sustained-release formulation of morphine. Araico, A; Peris, JE; Saadeddin, A; Torres-Molina, F, 2009)	0.83
" The morphine-dependent model mice were established by injection on dosage increasing by degrees."	( [Study on the detoxification of alcohol extracts from orientvine and its effective component on withdrawal syndromes of morphine]. Mo, ZX; Wang, CY; Zhang, GM, 2009)	1.08
" Intrathecal opioid dosing is limited, however, by opioid-related side effects, most importantly respiratory depression."	( Postoperative analgesia after radical prostatectomy with high-dose intrathecal morphine and intravenous naloxone: a retrospective review. Andrykowski, M; Rebel, A; Sloan, P, )	0.36
" The naive-participant study evaluated the effects of sleep deprivation alone, morphine alone and the combination; the tolerant-participant study compared day-to-day effects of alternate-daily-dosed buprenorphine and the combination of buprenorphine on the dosing day with sleep deprivation."	( Utility of saccadic eye movement analysis as an objective biomarker to detect the sedative interaction between opioids and sleep deprivation in opioid-naive and opioid-tolerant populations. Gentgall, M; Grace, PM; Rolan, PE; Stanford, T, 2010)	0.59
"ICR mice were used to generate antagonist dose-response curves with intraperitoneal (i."	( In vivo characterization of the opioid antagonist nalmefene in mice. Bilsky, EJ; Giuvelis, D; Lowery, JJ; Osborn, MD; Skorput, AG, 2010)	0.36
" Morphine at a dosage of 10 mg showed the best and most long-lasting analgesic efficiency."	( Analgesic effects of intra-articular morphine in patients with temporomandibular joint disorders: a prospective, double-blind, placebo-controlled clinical trial. Mühling, J; Wiechnik, J; Ziegler, CM, 2010)	1.54
" To determine the dosing frequency of sustained-release opioids (morphine, oxycodone, and transdermal fentanyl) and the prevalence of end-of-dose failure in clinical practice, a patient-reported survey was performed."	( The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: a Korean multicenter study. Ahn, JS; Kim, DY; Kim, SY; Ryoo, BY; Shin, DB; Song, HS; Yim, CY, 2010)	0.6
"8% of these patients took medication earlier than the prescribed dosing schedule."	( The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: a Korean multicenter study. Ahn, JS; Kim, DY; Kim, SY; Ryoo, BY; Shin, DB; Song, HS; Yim, CY, 2010)	0.36
" End-of-dose failure is suggested to explain increased dosing frequency, and patients reported that adequate pain relief lasted for less time than was stated in the manufacturers' prescription recommendation."	( The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: a Korean multicenter study. Ahn, JS; Kim, DY; Kim, SY; Ryoo, BY; Shin, DB; Song, HS; Yim, CY, 2010)	0.36
"Patient Controlled Analgesia is a useful technic to deliver morphine analgesia via a programmable pump: the patient himself choose to self-administer a bolus dose (usually morphine); the dosage is calculated and prescribed according to the level of pain, limits of dose and period of interdiction are planned."	( [Patient controlled analgesia in children]. Fournier-Charrière, E; Tourniaire, B, 2010)	0.6
" SO-3 co-administered with morphine left-shift the dose-response curve of morphine in mice acetic acid writhing test and significantly potentiated morphine analgesia in rat formalin test."	( Spinal antinociception of synthetic omega-conotoxin SO-3, a selective N-type neuronal voltage-sensitive calcium channel blocker, and its effects on morphine analgesia in chemical stimulus tests in rodent. Dong, HJ; Gong, ZH; Huang, PT; Liu, YL; Su, RB; Yan, LD; Zhang, L; Zhou, PL, 2010)	0.86
") Moreover, the percentage of patients needing to increase the morphine dosage (40."	( Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: a safe and effective approach to cancer pain. Cruto, M; Debernardi, F; Massucco, P; Moselli, NM; Savojardo, M, 2010)	0.83
"Recently, a new oral prolonged-release formulation of morphine sulfate for once-daily dosing has been developed based on an injection-molded matrix (abuse-deterrent, prolonged-release erodible matrix [ADPREM])."	( Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory cr Andersen, C; Burneckis, A; Jespersen, L; Ridgway, D; Sopata, M, 2010)	0.83
" Steady-state trough concentrations of morphine and its metabolites in plasma before morning dosing were similar after either treatment period."	( Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory cr Andersen, C; Burneckis, A; Jespersen, L; Ridgway, D; Sopata, M, 2010)	0.85
"In this study, dosing with ADPREM at intervals of 24 hours was therapeutically equivalent to CRM dosed at intervals of 12 hours."	( Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory cr Andersen, C; Burneckis, A; Jespersen, L; Ridgway, D; Sopata, M, 2010)	0.58
" Acute injection of scopolamine shifted the morphine dose-response curved leftward and downward and acute injection of morphine shifted the scopolamine and nicotine dose-response curves leftward and downward."	( Interactions between morphine, scopolamine and nicotine: schedule-controlled responding in rats. France, CP; Li, JX; Li, X, 2010)	0.94
" For this purpose, morphine hydrochloride injection is thought to be the best dosage form because it has advantages of: (1) quickness in varying the amount, (2) immediate rescue efficacy, and (3) usefulness in case of ingestion."	( [Opioid rotation in the home medical care service]. Sugimoto, Y, 2009)	0.68
" However, dose-response curves for morphine self-administration have not yet been examined and nor strain differences might be evident."	( Strain differences in the dose-response relationship for morphine self-administration and impulsive choice between Lewis and Fischer 344 rats. Ambrosio, E; Crespo, JA; García-Lecumberri, C; Higuera-Matas, A; Martín, S; Miguéns, M; Nicanor, C; Torres, I, 2011)	0.89
" Over the following 6 months, the dosage was gradually titrated up to 4 mg/day with satisfactory pain control without significant side effects."	( Respiratory failure following delayed intrathecal morphine pump refill: a valuable, but costly lesson. Chiravuri, S; Couch, JP; Liu, H; Ruan, X; Shah, RV; Wang, F, )	0.38
" Moreover, whereas plasma concentration of morphine markedly decreased up to 4h (C(4h)) after subchronic administration of the opioid, multiple dosing of the morphine+metamizol combination produced an accumulation of the drug in plasma (P<0."	( Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats. Cortés-Arroyo, AR; Domínguez-Ramírez, AM; López, JR; López-Muñoz, FJ; Y de la Peña, MH, 2010)	0.93
" Initiation of opioid therapy must consider gradual dose titration of the drug until the minimum effective and maximum tolerated dosage for each patient is found."	( Effects of opioid rotation in chronic pain patients: ORTIBARN study. Canneti, A; Gatti, A; Luzi, M; Mammucari, M; Mediati, RD; Reale, C; Sabato, AF; Vellucci, R, 2010)	0.36
" Following start therapy with oral NR morphine at a dosage of 5 mg or 10 mg every 4 hours, rotation to an SR opioid of a different type from that previously administered was carried out."	( Effects of opioid rotation in chronic pain patients: ORTIBARN study. Canneti, A; Gatti, A; Luzi, M; Mammucari, M; Mediati, RD; Reale, C; Sabato, AF; Vellucci, R, 2010)	0.63
" Patients with either cancer-related or non-cancer pain who experienced >2 intensive episodic pain breakouts per day were prescribed immediate-release (IR) morphine sulphate (10 mg to 20 mg as needed) every 4 hours (around-the-clock) and allowed one rescue dose of IR morphine (equal to one additional administration of the dosage taken at fixed times) for any episodic pain breakouts."	( Time to pain relief after immediate-release morphine in episodic pain: the TIME study. Lo Presti, C; Mammucari, M; Muriess, D; Roscetti, A, 2010)	0.82
" Dependence was established using a noncontingent morphine dosing procedure that has been previously verified to maintain dependence while allowing for daily behavioral observation during a withdrawn state."	( Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats. Cooper, ZD; Shi, YG; Woods, JH, 2010)	0.61
"Morphine withdrawal enhanced remifentanil self-administration, resulting in an upward and rightward shift of the descending limb of the dose-response curve, and increased operant responding for both food reinforcers."	( Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats. Cooper, ZD; Shi, YG; Woods, JH, 2010)	1.8
" No differences were observed in the morphine dose-response curve in suppression of acute nociception (i."	( Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity. King, T; Lian, B; Ossipov, MH; Porreca, F; Vera-Portocarrero, L, 2010)	0.63
" A 7-day intrathecal treatment with morphine (15 μg/day) produced tolerance to its analgesic effects as well as a rightward shift in the dose-response curve to its antinociceptive effects."	( Morphological evidence for the involvement of microglial p38 activation in CGRP-associated development of morphine antinociceptive tolerance. Chabot, JG; Ma, W; Quirion, R; Wang, Z, 2010)	0.85
" This study sought to (1) describe the variability in intravenous opioid dosing and (2) compare the outcomes that result from the most commonly prescribed opioid doses."	( Intravenous opioid dosing and outcomes in emergency patients: a prospective cohort analysis. Feng, C; Hays, DP; O'Connor, AB; Zwemer, FL, 2010)	0.36
"We found marked opioid dosing variability and infrequent opioid dose titration."	( Intravenous opioid dosing and outcomes in emergency patients: a prospective cohort analysis. Feng, C; Hays, DP; O'Connor, AB; Zwemer, FL, 2010)	0.36
" This can prevent the development of intractable PHN and attenuate morphine antinociceptive tolerance and further improve the efficacy of morphine and therefore reducing its dosage and side effects."	( The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia. Chen, S; Hui, H; Xue, Y; Zhang, D, 2010)	0.93
" In both (placebo and morphine pellets), dose-response curves for M, FEN and TRM, individually and combined were obtained, and the doses that produced 50% inhibition (ED(50)) were determined."	( Antinociceptive effects of morphine, fentanyl, tramadol and their combination, in morphine-tolerant mice. Miranda, HF; Puig, MM; Romero, A, 2010)	0.97
" When subjects who vomited during the 12-hour dosing interval were excluded, the confidence interval for AUC0-t and AUCinf fell within the 80%-125% range, but the lower limit for Cmax was 76."	( The relative bioavailability of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®) and an extended release morphine sulfate capsule formulation (KADIAN®) in healthy adults under fasting conditions. Boudriau, S; Ciric, S; Johnson, FK; Kisicki, JC; Stauffer, J, 2011)	0.65
"5-fold leftward shift of the morphine dose-response curve in morphine-tolerant rats, and this was associated with reversal of the up-regulated NR1 and NR2B subunits in the synaptosome fraction."	( Purinergic P2X receptor regulates N-methyl-D-aspartate receptor expression and synaptic excitatory amino acid concentration in morphine-tolerant rats. Chen, YF; Cheng, PY; Tai, YH; Tsai, RY; Wong, CS, 2010)	0.86
" Plasma samples were collected just before dosing through 72 hours postdose for pharmacokinetic analyses of morphine, and through 168 hours postdose for naltrexone and its major metabolite 6-β-naltrexol."	( Food effects on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules. Boudriau, S; Ciric, S; Johnson, F; Stauffer, J; Swearingen, D, 2010)	0.84
"This prospective randomized double-blind dose-response study aimed to determine the ED₅₀ and ED₉₅ of intrathecal levobupivacaine combined with morphine and sufentanil for elective Caesarean delivery."	( ED₅₀ and ED₉₅ of intrathecal levobupivacaine with opioids for Caesarean delivery. Allaouchiche, B; Boselli, E; Bouvet, L; Chassard, D; Da-Col, X; Daléry, F; Dantony, E; Ruynat, L, 2011)	0.57
"randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing."	( A double-blind, placebo-controlled study of dual-opioid treatment with the combination of morphine plus oxycodone in patients with acute postoperative pain. Kelen, R; Richards, P; Stern, W; Webster, L, )	0.35
" Despite this growing trend, there is very little information available to guide practitioners with regard to patient selection as well as intrathecal drug dosing paradigms."	( Patient selection and trialing techniques utilizing low-dose intrathecal morphine for chronic nonmalignant pain: a report of two cases. Grider, JS; Harned, ME; Sloan, PA, )	0.36
" More studies are needed to characterize the combined effects of multiple genes and demographic as well as clinical variables in predicting the correct morphine dosage and corresponding opioid-related side effects."	( Combined catechol-O-methyltransferase and mu-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Gabovits, B; Kolesnikov, Y; Levin, A; Veske, A; Voiko, E, 2011)	0.79
"This casuistic reports on a 59-year-old pain patient taking normal dosage Tramadol as analgetic drug, who suffered from chronic dizziness leading to immobilisation for more than 9 months."	( [Chronic dizziness in a pain patient--pharmacogenomic identification of tramadol as cause]. Barth, J; Eichhorn, A, 2010)	0.36
"Model validation procedures are crucial when models are to be used to develop new dosing algorithms."	( Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Choonara, I; Danhof, M; DeJongh, J; Knibbe, CA; Krekels, EH; Lynn, AM; Tibboel, D; van der Marel, CD; van Lingen, RA, 2011)	0.59
" It is herewith justified to undertake a proof-of-principle approach in the development of rational dosing recommendations - namely, performing a prospective clinical trial in which the model-based dosing algorithm is clinically evaluated."	( Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Choonara, I; Danhof, M; DeJongh, J; Knibbe, CA; Krekels, EH; Lynn, AM; Tibboel, D; van der Marel, CD; van Lingen, RA, 2011)	0.59
"Blood conservation; the area of greatest clinical variability was seen in dosing regimes for Tranexamic acid."	( Blood conservation and pain control in scoliosis corrective surgery: an online survey of UK practice. Bird, S; McGill, N, 2011)	0.37
" Lethal dose to cause 50 % death (LD50) was calculated from a dose-response curve (100-5000 mg/kg body wt."	( Chemical composition, acute toxicity, and antinociceptive activity of the essential oil of a plant breeding cultivar of basil (Ocimum basilicum L.). Alves, PB; Antoniolli, AR; Blank, AF; de Araujo, BS; Estevam, Cdos S; Lira, AF; Marchioro, M; Onofre, AS; Venâncio, AM, 2011)	0.37
" Using an unbiased, three-chamber conditioned place preference (CPP) paradigm the dose-response function for nicotine CPP was tested in GAL-/- and GAL+/+ mice."	( Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference. Hales, CA; Henehan, RM; Neugebauer, NM; Picciotto, MR, 2011)	0.37
"The overall impact of chronic pain on the response to opioids is ambiguous in the literature, and comparisons between human and animal studies are complicated by vast differences between the manner and dosage of opioids given to humans treated for pain in comparison to rodents as well as a lack of healthy participant studies examining the impact of chronic opioids."	( Chronic inflammatory pain does not attenuate the development of tolerance to chronic morphine in adult male rats. Boyette-Davis, JA; Fuchs, PN; Uhelski, ML, 2011)	0.59
" The IC(50) value of SB-612111 estimated from dose-response curves is 87."	( Quantitative study of the antagonistic effect of (-)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111) on nociceptin/orphanin FQ-mediated potassium channel activation in rat periaqueducta Chiou, LC; Jiang, F; Liao, YY, 2011)	0.37
"To observe the effect of parecoxib on morphine dosage in patient-controlled analgesia (PCA) following thoracoscope-assisted thoracotomy."	( [Effects of parecoxib on morphine dosage in postoperative patient-controlled analgesia following thoracoscope-assisted thoracotomy]. Gu, MN; Hou, XM; Liu, GW; Liu, XJ; Xiao, JF, 2011)	0.94
"The application of parecoxib may reduce the dosage of morphine in PCA following thoracoscope-assisted thoracotomy and results in good analgesic effect without affecting the patients respiratory function and sputum elimination."	( [Effects of parecoxib on morphine dosage in postoperative patient-controlled analgesia following thoracoscope-assisted thoracotomy]. Gu, MN; Hou, XM; Liu, GW; Liu, XJ; Xiao, JF, 2011)	0.92
"The effectiveness of intrathecal opioids (ITOs) for postoperative analgesia has been limited by reduced opioid dosing because of opioid-related side effects, most importantly respiratory depression."	( Retrospective analysis of high-dose intrathecal morphine for analgesia after pelvic surgery. Andrykowski, M; Rebel, A; Sloan, P, )	0.39
" In the switching study DDD indicated a reduction in analgesic dosing and OMEQ an increase when switching from WHO step II to III."	( Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses. Borchgrevink, P; Dale, O; Fredheim, O; Hamunen, K; Mellbye, A; Svendsen, K, 2011)	0.61
"OMEQ reflects clinical dosing better than DDD, and can give additional insight into opioid consumption when combined with DDD."	( Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses. Borchgrevink, P; Dale, O; Fredheim, O; Hamunen, K; Mellbye, A; Svendsen, K, 2011)	0.61
" According to a third of the respondents, the level of sedation was not related to the required level of symptom relief nor were changes in dosage based on the severity of symptoms."	( Palliative sedation at home in the Netherlands: a nationwide survey among nurses. Brinkkemper, T; Deliens, L; Eliel, M; Klinkenberg, M; Perez, RS; Rietjens, JA; Zuurmond, WW, 2011)	0.37
" One patient with high morphine dosage (20 mg/d), interestingly, did not show any withdrawal symptoms."	( Ziconotide: A rapid detoxification protocol for the conversion from intrathecal morphine--the Raffaeli Detoxification Model. Balestri, M; Caminiti, A; Ferioli, I; Monterubbianesi, MC; Raffaeli, W; Righetti, D; Sarti, D, )	0.67
" While, some anesthetics and synthetic narcotics used to reduce pain are reported to suppress immune activities depending on the kind of medication and the dosing strategy."	( [A single administration of morphine suppresses the reduction of the systemic immune activity caused by acute inflammatory pain in rats]. Arai, K; Guo, SY; Hisamitsu, T; Nakamura, A; Okada, M; Saito, Y; Sakaue, S; Sunagawa, M; Tanigawa, H, 2011)	0.66
" Additionally, systematic reviews of these placebo-controlled trials have failed to determine clinically meaningful dose-response effect."	( Analgesic effectiveness of dipyrone (metamizol) for postoperative pain after herniorrhaphy: a randomized, double-blind, dose-response study. Alvarez, HD; Chaparro, LE; Joaqui, W; Lezcano, W, 2012)	0.38
"This trial shows a dose-response effect of 40 mg/kg over 15 mg/kg of intravenous dipyrone based on better movement-induced pain control, lower morphine consumption and fewer opioid-related side effects."	( Analgesic effectiveness of dipyrone (metamizol) for postoperative pain after herniorrhaphy: a randomized, double-blind, dose-response study. Alvarez, HD; Chaparro, LE; Joaqui, W; Lezcano, W, 2012)	0.58
" Dosing strategies based on patient weight may not be necessary in this patient population."	( Patient weight as a predictor of pain response to morphine in the emergency department. Biggs, AD; Erstad, BL; Patanwala, AE, 2011)	0.62
" Equal volumes of three plasma samples corresponding to each time point of three discretely dosed rats with different compounds were pooled (cassette analysis)."	( High-throughput analysis of standardized pharmacokinetic studies in the rat using sample pooling and UPLC-MS/MS. Betnér, I; Briem, S; Bueters, T; Dahlström, J; Kvalvågnaes, K, 2011)	0.37
" Additionally, the use of the protocol described in this article suggests that the dose-response relationship following opioid cessation is in the 50-400 μg/d range for intrathecal morphine and that tolerance may be reversed during the 6 week opioid-free period."	( Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Etscheidt, MA; Grider, JS; Harned, ME, )	0.32
" Dose-response curves were generally quantal under the FR and graded under the FI schedules, but highly variable among subjects under the FI."	( Drug discrimination in pigeons trained to discriminate among morphine, U50488, a combination of these drugs, and saline. Li, M; McMillan, DE; Wessinger, WD, 2011)	0.61
") increased locomotion along an inverted U-shaped dose-response curve in adolescent, late adolescent, and adult male C57BL/6J mice."	( Morphine-induced motor stimulation, motor incoordination, and hypothermia in adolescent and adult mice. France, CP; Javors, MA; Koek, W, 2012)	1.82
"The purpose of this study was to examine the effects of a clinically relevant opioid on the production of augmented breaths (ABs) in unanesthetized animals breathing normal room air, using a dosage which does not depress breathing."	( The "other" respiratory effect of opioids: suppression of spontaneous augmented ("sigh") breaths. Azubike, E; Bell, HJ; Haouzi, P, 2011)	0.37
" Dose-response studies show that neuraxial morphine appears to have an analgesic efficacy 'ceiling'."	( Neuraxial morphine and respiratory depression: finding the right balance. Carvalho, B; Gutierrez, MC; Sultan, P, 2011)	1.03
"Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known."	( Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes. Bell, MC; Dampier, CD; Hsu, L; Keefer, J; Kim, HY; Krishnamurti, L; Mack, AK; McClish, D; McKinlay, SM; Miller, ST; Minniti, CP; Osunkwo, I; Seaman, P; Smith, WR; Telen, MJ; Wager, CG; Weiner, DL, 2011)	0.37
" There were no significant differences between the extrapleural and epidural block groups with regard to VAS at rest and during movement assessed at 4, 12, 24, 36, and 48 hours after surgery, dosage of intravenous morphine (extrapleural: 12."	( Comparison of the analgesic effects of continuous extrapleural block and continuous epidural block after video-assisted thoracoscopic surgery. Endo, S; Endo, T; Hotta, K; Inoue, S; Sata, N; Seo, N; Taira, K; Takeuchi, M, 2011)	0.56
" Using a Delphi study method, physicians were asked to rank preferences of drug and dosing schedule for first-line opioid, antiemetic, and laxative for the treatment of adults with chronic pain due to cancer and other life-threatening conditions."	( Strategic pain management: the identification and development of the IAHPC opioid essential prescription package. Bennett, MI; Bruera, E; De Lima, L; Nekolaichuk, C; Ripamonti, CI; Vignaroli, E; Wenk, R, 2012)	0.38
" Tolerance to ULD-OIH develops with repeated dosing in rats."	( Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats. Holtman, JR; Sloan, PA; Wala, EP, )	0.39
" Finally, analysis of ambulatory activity and body weight (BW) changes reveal that motivational and cognitive effects are totally independent of caloric and/or motor effects of opiate dosing and withdrawal."	( Increased motivation to eat in opiate-withdrawn mice. Contarino, A; Rouibi, K, 2012)	0.38
" But in the absence of dose-response data for morphine, this suggestion seems imprudent."	( The dose-response relation for the antinociceptive effect of morphine in a fish, rainbow trout. Jones, SG; Kamunde, C; Lemke, K; Stevens, ED, 2012)	0.88
"In order to reduce postoperative opioid requirement, extrapleural local anaesthetic infusion dosing recommendations and guidelines for extrapleural catheter insertion were developed in our institution for 'extubatable' neonates requiring short-gap neonatal tracheo-oesophageal fistula/oesophageal atresia repair (via thoracotomy) and audited prospectively."	( Audit of extrapleural local anaesthetic infusion in neonates following repair of tracheo-oesophageal fistulae and oesophageal atresia via thoracotomy. Chalkiadis, GA; Clarnette, TD; Dowden, SJ; McNally, CM; Palmer, GM; Penrose, S; Smith, KR; Thalayasingam, P; Tingay, DG, 2012)	0.38
" These results suggest this dosing regimen of gabapentin is not efficacious in improving outcomes in patients undergoing shoulder arthroscopy under general anesthesia with an interscalene block."	( Perioperative administration of gabapentin for shoulder arthroscopy: a prospective, randomized, double-blind, placebo-controlled study. Bowen, K; Goff, J; Maye, J; Mohan, E; Osborne, L; Spence, D, 2011)	0.37
"Although opioids are widely accepted as standard therapy for treating acute postoperative pain, the frequent occurrence of adverse events (AEs) and the substantial burden on the patient and the costs of care are a barrier to optimal dosing and adherence to prescribed treatment."	( Efficacy and safety of dual-opioid therapy in acute pain. Webster, L, 2012)	0.38
" After bilaterally implantation of cannulae into the CA1 and/or VTA in adult male Wistar rats weighing 210-310 g, dose-response effects of different doses of intra-VTA morphine (0."	( Role of D1/D2 dopamine receptors in the CA1 region of the rat hippocampus in the rewarding effects of morphine administered into the ventral tegmental area. Esmaeili, MH; Haghparast, A; Kermani, M; Parvishan, A, 2012)	0.79
" This may be because of wide variations in age, weight, dosing ranges, and off-label practices, but few studies exclusively devoted to examining pediatric 10-fold error have identified the circumstances and mechanisms that lead to such errors."	( Tenfold medication errors: 5 years' experience at a university-affiliated pediatric hospital. Doherty, C; Mc Donnell, C, 2012)	0.38
" Morphine dosing based on patient weight alone is not necessary in adults in the ED."	( Should morphine dosing be weight based for analgesia in the emergency department? Amini, R; Desai, A; Edwards, CJ; Patanwala, AE; Stolz, L; Stolz, U, )	1.5
" VAS and whole dosage of morphine were compared between two groups every 6 hours."	( Analgesic effects of ketamine infusion on postoperative pain after fusion and instrumentation of the lumbar spine: a prospective randomized clinical trial. Abrishamkar, S; Eshraghi, N; Feizi, A; Rafiei, A; Rahmani, P; Talakoub, R, 2012)	0.68
"The objective was to assess the efficacy of patient-controlled analgesia (PCA) in the emergency department (ED) and to compare two PCA dosing regimens."	( Efficacy of patient-controlled analgesia for patients with acute abdominal pain in the emergency department: a randomized trial. Bijur, P; Birnbaum, A; Gallagher, EJ; Schechter, C; Touger, R; Tufaro, V, 2012)	0.38
" When rats were co-infused with MOR and NAL, MOR-induced effects were not reversed by either dosage of NAL, and some measures of MOR-induced movement suppression were enhanced by NAL at the 1x dosage."	( The role of mu-opioid receptor signaling in the dorsolateral periaqueductal gray on conditional and unconditional responding to threatening and aversive stimuli. Blair, HT; Halladay, LR, 2012)	0.38
"Our findings suggest a role for our rooming-in program in mitigating the relationship between maternal methadone dosage and the need to treat opiate withdrawal in the newborn."	( A rooming-in program to mitigate the need to treat for opiate withdrawal in the newborn. Abrahams, RR; Hodgson, ZG, 2012)	0.38
" More importantly, subcutaneous co-administrations or even single dose of CBIO completely prevented or reversed morphine tolerance to analgesia (exhibited by a single dose or a dose-response curve of morphine) in both formalin-induced acute phase nociception and tonic phase pain."	( Interactions of the potent D-amino acid oxidase inhibitor CBIO with morphine in pain and tolerance to analgesia. Gong, N; Hashimoto, K; Ma, AN; Wang, HL; Wang, YC; Wang, YX, 2012)	0.83
"The aims of this study were to investigate the dose-response relationship (n=7) and the potential absorption of topical morphine (n=5) across oral mucosa in children with oral mucositis."	( Topical morphine for oral mucositis in children: dose finding and absorption. Aagaard, G; Hansen, SH; Henneberg, SW; Nielsen, BN; Rømsing, J; Schmiegelow, K, 2012)	1.02
"A decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study."	( Topical morphine for oral mucositis in children: dose finding and absorption. Aagaard, G; Hansen, SH; Henneberg, SW; Nielsen, BN; Rømsing, J; Schmiegelow, K, 2012)	0.81
"We investigated the safety and efficacy of the bilateral periarticular multimodal drug injection (PMDI) at a reduced dosage in patients undergoing simultaneous bilateral total knee arthroplasty (SBTKA)."	( Use of reduced-dose periarticular injection for pain management in simultaneous bilateral total knee arthroplasty. Chang, CB; Jeon, YT; Kang, YG; Kim, TK; Koh, IJ; Song, J, 2012)	0.38
"The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model."	( Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects. Hoeben, E; Mangold, B; Reitmeir, P; Rusch, S; Schaffler, K; Smit, JW; Upmalis, D, 2012)	0.82
" MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception."	( Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat. Bobeck, EN; Haseman, RA; Hong, D; Ingram, SL; Morgan, MM, 2012)	0.81
" An increase in dosing variability was observed with increasing age."	( The relationship between age and morphine infusion rate in children. Anderson, BJ; Liley, A; Taylor, J, 2013)	0.67
" In part 1 of the study, patients were dosed every 5 minutes for the first 65 minutes (up to 13 doses) with study drug, provided that vital signs criteria were met."	( Analgesic efficacy and tolerability of intravenous morphine versus combined intravenous morphine and oxycodone in a 2-center, randomized, double-blind, pilot trial of patients with moderate to severe pain after total hip replacement. Bäthis, H; Böhmer, A; Joppich, R; Kelen, R; Lefering, R; Neugebauer, E; Otto, C; Petzke, F; Richards, P; Stern, W; Treptau, T; Zarghooni, K, 2012)	0.63
" Two chronic pain patients with loss of pain control following dosage increase in levothyroxine supplementation are presented."	( Loss of antinociceptive effectiveness of morphine and oxycodone following titration of levothyroxine: case reports and a brief review of published literature. Herndon, CM; Kearney, TC; Lindsay, TJ; Matoushek, TA, )	0.4
"Pain patients with implanted catheters and pumps (range: 127 to 2165 days), receiving a stable dosing (>1 week) of IT morphine by infusion, were entered into the study."	( Characteristics of distribution of morphine and metabolites in cerebrospinal fluid and plasma with chronic intrathecal morphine infusion in humans. Wallace, M; Yaksh, TL, 2012)	0.86
" While morphine dosage increased before HBOT (median morphine dose 23 mg per day and 35."	( Hyperbaric oxygen therapy for vaso-occlusive crises in nine patients with sickle-cell disease. Aras, N; Borne, M; Brinquin, L; Fain, O; Letellier, E; Stirnemann, J, 2012)	0.83
" Finally, in order to identify whether morphine sensitized pro-inflammatory cytokine release, spinal cord was isolated two days after morphine dosing for five days , and slices stimulated ex vivo with lipopolysaccharide."	( Prior exposure to repeated morphine potentiates mechanical allodynia induced by peripheral inflammation and neuropathy. Berkelhammer, D; Bowlin, M; Ellis, A; Grace, PM; Loram, LC; Maier, SF; Skarda, B; Strand, KA; Taylor, FR; Watkins, LR, 2012)	0.95
"Intra-operative dosing of sufentanil significantly influenced post-operative morphine consumption, pain and hyperalgesia."	( The impact of intra-operative sufentanil dosing on post-operative pain, hyperalgesia and morphine consumption after cardiac surgery. Fechner, J; Ihmsen, H; Jeleazcov, C; Schüttler, J, 2013)	0.84
" In March 2011, all dosage forms of Embeda® were recalled because the product failed to meet routine stability standards, and its return date to the market is currently unknown."	( Will abuse-deterrent formulations of opioid analgesics be successful in achieving their purpose? Bannwarth, B, 2012)	0.38
" In the present study, a digoxin dose-response curve was conducted to observe the effects on naloxone-precipitated withdrawal and locomotor activity in mice."	( A comparison of the effects of digoxin, ouabain and milrinone on naloxone-precipitated withdrawal syndrome in mice. Bai, YL; Chen, YY; Chu, QJ; Li, J; Li, WJ; Zhang, Q, 2012)	0.38
"The Tekscan(®) WB measurement system was used in MIA rats to examine the acute and chronic dosing effects of drugs that targeted different mechanisms."	( Pharmacological validation of early and late phase of rat mono-iodoacetate model using the Tekscan system. Elmes, SJ; McIntosh, F; Perkins, MN; Rashid, MH; Theberge, Y, 2013)	0.39
" We tested SB 334867 in three doses (10, 20 and 30 mg/kg), TCS-OX2-29 in two doses (5 and 10 mg/kg) and morphine with highest effective dose based on our dose-response experiment (5 mg/kg)."	( The differential effects of OX1R and OX2R selective antagonists on morphine conditioned place preference in naïve versus morphine-dependent mice. Dehpour, AR; Esmaeili, B; Ghaffarpour, M; Javadi-Paydar, M; Mirbaha, H; Motiei-Langroudi, R; Tabaeizadeh, M; Tahsili-Fahadan, P, 2013)	0.84
" Animals were analyzed for morphine dose-response using Hot Plate test."	( Periaqueductal gray neuroplasticity following chronic morphine varies with age: role of oxidative stress. Bajic, D; Berde, CB; Commons, KG, 2012)	0.92
" However, the optimal dosing regimen remains unclear."	( Closed-loop double-vasopressor automated system to treat hypotension during spinal anaesthesia for caesarean section: a preliminary study. Sia, AT; Sng, BL; Tan, HS, 2012)	0.38
" In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose-response relationship of this side effect."	( Augmented breaths ('sighs') are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats. Bell, HJ; Pankuch, G, 2013)	0.65
" Dose-response curves for morphine (0."	( Flupirtine enhances the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis. Cooke, I; Goodchild, CS; Kolosov, A; Williams, ED, 2012)	0.93
" The effective doses, for 20%, 50%, and 80% response (ED(20), ED(50), and ED(80), respectively), of each drug were calculated using least squares linear regression analysis, and then dose-response curves were compared."	( Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Keyhanfar, F; Shamsi Meymandi, M, 2013)	0.65
" No difference was observed between slopes of dose-response curves."	( Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Keyhanfar, F; Shamsi Meymandi, M, 2013)	0.65
"In this animal model of visceral pain, all three drugs exhibited parallel dose-response curves."	( Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Keyhanfar, F; Shamsi Meymandi, M, 2013)	0.65
" We also evaluated the postoperative effects of intraoperative analgesic dosage in patients after this surgery."	( [Postoperative pain management by intravenous patient-controlled analgesia in patients undergoing upper abdominal gastrointestinal surgery]. Kajiyama, S; Kawamoto, M; Niihata, T; Sugimoto, Y, 2012)	0.38
" Our results can be used to help guide intrathecal morphine dosing in cesarean delivery based on patient preference for analgesia versus side effects."	( Intrathecal morphine 100 and 200 μg for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects. Carvalho, B; Riley, ET; Wong, JY, 2013)	1.02
"Bimodal dose-response relationships have been demonstrated in animals and humans following morphine administration."	( Dual effect of morphine in long-term social memory in rat. Bianchi, E; Ghelardini, C; Menicacci, C, 2013)	0.96
"Acupuncture may be a safe and feasible treatment to assist mothers to reduce their dosage of methadone."	( Auricular acupuncture for chemically dependent pregnant women: a randomized controlled trial of the NADA protocol. Abrahams, R; Demorest, LC; Janssen, PA; Kelly, A; Thiessen, P, 2012)	0.38
"Opioid choice was tightly linked with equianalgesic dose, with the median hydromorphone dosage more than 50 percent higher than the dosage of morphine."	( Why do emergency providers choose one opioid over another? A prospective cohort analysis. O'Connor, AB; Rao, A, )	0.33
" Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood."	( Maternally administered sustained-release naltrexone in rats affects offspring neurochemistry and behaviour in adulthood. Dunlop, SA; Farid, WO; Hulse, GK; Krstew, EV; Lawrence, AJ; Tait, RJ, 2012)	0.38
"The correct dosage of lactulose for the prevention of oral morphine-induced constipation is 60 ml/d."	( [Clinical observation of prophylactic lactulose for prevention of oral morphine-induced constipation]. Gu, XQ; Jiao, XD; Lan, HF; Lou, C; Qian, JX; Wang, MM; Wang, Z; Xiao, M; Yuan, LY, 2012)	0.86
" placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs."	( Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials. Bennett, MI; Fullarton, JR; Jandhyala, R, 2013)	0.63
"Compounds were dosed in conscious rats and mice."	( Pharmacological comparison of peristaltic effects in rats and mice. Larson, KJ; Martin, RL; Polakowski, JS; Shaughnessy, TK, )	0.13
" Pretreatment with gallein produced a dose-dependent potentiation of morphine-mediated antinociception, producing up to a 10-fold leftward shift in the morphine dose-response curve and extending the duration of antinociception induced by a single dose of morphine."	( Inhibition of Gβγ-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward. Bidlack, JM; Carey, AN; Hoot, MR; McLaughlin, JP; Reilley, KJ; Sypek, EI, 2013)	0.88
" Increasing the dosage of spinal morphine does not decrease postoperative meperidine consumption, but may lead to respiratory depression in rare cases."	( Low-dose spinal morphine for post-thoracotomy pain: a prospective randomized study. Lertpaitoonpan, W; Phanchaipetch, T; Pongpayuha, P; Sanansilp, V; Suksompong, S; von Bormann, B, 2013)	1.02
" Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations."	( Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg. Hajj, A; Khabbaz, L; Laplanche, JL; Peoc'h, K, 2013)	0.39
" Dosing was higher in the compounded group."	( Intrathecal administration of Infumorph® vs compounded morphine for treatment of intractable pain using the Prometra® programmable pump. Barsa, J; Bromberg, TA; Creamer, M; Deer, T; Dunbar, E; Dwarakanath, G; Jaffe, T; Navalgund, Y; Padda, G; Rosen, SM; Yearwood, TL, 2013)	0.64
"92 % was obtained when the dosage ratio of morphine to PLLA-PEG-PLLA reached 1:5, and the encapsulation efficiency can be as high as 87."	( Preparation, characterization and in vitro release properties of morphine-loaded PLLA-PEG-PLLA microparticles via solution enhanced dispersion by supercritical fluids. Chen, F; Chen, X; Gao, H; Gu, J; Huang, Z; Liao, X; Yang, Y; Yao, Y; Yin, G, 2013)	0.89
" Data extracted were age, gender, type of operations, dosage of spinal morphine, and frequency, and severity of adverse effects (nausea, vomiting, and pruritus)."	( Nausea, vomiting and pruritus induced by intrathecal morphine. Chinachoti, T; Nilrat, P; Samarnpiboonphol, P, 2013)	0.87
" Intravenous (IV) morphine was prescribed and dosed at the discretion of the treating physician; physicians were advised to target a 50% reduction in pain or per-patient request."	( A comparison of ultrasound-guided three-in-one femoral nerve block versus parenteral opioids alone for analgesia in emergency department patients with hip fractures: a randomized controlled trial. Beaudoin, FL; Haran, JP; Liebmann, O, 2013)	0.72
" The risk increased significantly as the morphine dosage increased to 170 mg/year of treatment."	( Association of intensive morphine treatment and increased stroke incidence in prostate cancer patients: a population-based nested case–control study. Kao, CH; Lee, CW; Liang, JA; Muo, CH; Sung, FC, 2013)	0.96
" The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans."	( Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice. Ko, MC; Sukhtankar, DD, 2013)	0.58
" Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation."	( Oral morphine for cancer pain. Moore, RA; Wee, B; Wiffen, PJ, 2013)	1.19
" A dose-response curve was established for pregabalin at a fixed morphine dose and revealed that, at low doses, pregabalin dose-dependently enhanced the antinociceptive effects, while the opposite was true at high doses (17 and 25 mg/kg)."	( Assessment of the antinociceptive effects of pregabalin alone or in combination with morphine during acetic acid-induced writhing in mice. Keyhanfar, F; Shamsi Meymandi, M, 2013)	0.85
" Dosage of analgesic medication consumption was retrieved from patients' charts."	( Combined spinal and general anesthesia vs general anesthesia for robotic sacrocervicopexy: a randomized controlled trial. Awad, N; Lowenstein, L; Mustafa, S; Nasir, H; Segal, D, 2014)	0.4
"7, respectively) following dosing compared with MS (Emax 87."	( Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users. Goli, V; Levy-Cooperman, N; Mills, C; Setnik, B; Shram, M; Smith, I, )	0.35
") administration of the specific MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22, 3 nmol) increased morphine-induced analgesia and shifted the morphine dose-response curve to the left in rats."	( Activation of Mas oncogene-related gene (Mrg) C receptors enhances morphine-induced analgesia through modulation of coupling of μ-opioid receptor to Gi-protein in rat spinal dorsal horn. Chen, T; Couture, R; Hong, Y; Wang, D; Zhou, X, 2013)	0.84
") injections with the cannabinoid agonist WIN-55,212 (WIN) or its vehicle (VEH) for three consecutive days using a twice-daily, increasing dosage regimen (1 mg/kg day 1; 2 mg/kg day 2; 4 mg/kg day 3)."	( Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposure. Byrnes, EM; Johnson, NL; Vassoler, FM, 2013)	0.62
" Eighty per cent of patients were not asked about their ability to swallow solid, oral dosage forms by their physician."	( Challenges of treating patients with chronic pain with dysphagia (CPD): physician and patient perspectives. Carlson, DR; Kopecky, EA; Nalamachu, S; Pergolizzi, JV; Raffa, RB; Taylor, R; Varanasi, RK, 2014)	0.4
"A proportion of patients with chronic pain have dysphagia and cannot swallow solid, oral dosage forms, which creates a serious treatment challenge for pain specialists and other healthcare providers."	( Challenges of treating patients with chronic pain with dysphagia (CPD): physician and patient perspectives. Carlson, DR; Kopecky, EA; Nalamachu, S; Pergolizzi, JV; Raffa, RB; Taylor, R; Varanasi, RK, 2014)	0.4
" The PRC recommended revisions to the Maryland protocol that reflected recommendations in the EBG: weight-based dosing and repeat dosing of morphine."	( The implementation and evaluation of an evidence-based statewide prehospital pain management protocol developed using the national prehospital evidence-based guideline model process for emergency medical services. Alcorta, R; Brown, KM; Hirshon, JM; Ho, S; Lawner, B; Weik, TS; Wright, JL, 2014)	0.6
"We demonstrated that the implementation of a revised statewide prehospital pain management protocol based on an EBG developed using the National Prehospital Evidence-based Guideline Model Process was associated with an increase in dosing of narcotic pain medication consistent with that recommended by the EBG."	( The implementation and evaluation of an evidence-based statewide prehospital pain management protocol developed using the national prehospital evidence-based guideline model process for emergency medical services. Alcorta, R; Brown, KM; Hirshon, JM; Ho, S; Lawner, B; Weik, TS; Wright, JL, 2014)	0.4
" In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance."	( Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat. Aicher, SA; Ingram, SL; Mehalick, ML; Morgan, MM, 2013)	0.93
" This approach is intended to reduce the opioid subjective rewarding effects such as euphoria which are prominent following swallowing the dosage form without tampering."	( Sequestered naltrexone in sustained release morphine or oxycodone - a way to inhibit illicit use? Pergolizzi, JV; Raffa, RB; Taylor, R, 2014)	0.66
" dosing significantly inhibited opioid withdrawal induced depression in mice."	( Inhibitory effect of bacopasides on spontaneous morphine withdrawal induced depression in mice. Abbas, G; Abbas, M; Ali, G; Ali, SM; Ashfaq, M; Rauf, K; Subhan, F, 2014)	0.66
" We hypothesized that when used for pain, dronabinol has psychoactive effects in a dose-response relationship, whose peak effects are comparable with smoking marijuana."	( The subjective psychoactive effects of oral dronabinol studied in a randomized, controlled crossover clinical trial for pain. Edwards, RR; Issa, MA; Jamison, RN; Michna, E; Narang, S; Penetar, DM; Wasan, AD, 2014)	0.4
" Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment."	( Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone. Backmund, M; Beck, T; Haasen, C; Reimer, J; Ruckes, C; Schuler, C; Verthein, U; Walcher, S, 2014)	0.64
" This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use."	( Rates of fetal polydrug exposures in methadone-maintained pregnancies from a high-risk population. Delano, K; Gareri, J; Koren, G, 2013)	0.39
" This article presents an outline on performing a population PK/PD study and translating these results into rational dosing regimens, with the development and prospective evaluation of PK/PD derived evidence-based dosing regimen being discussed."	( Towards evidence-based dosing regimens in children on the basis of population pharmacokinetic pharmacodynamic modelling. Admiraal, R; Boelens, JJ; Bredius, RG; Knibbe, CA; Tibboel, D; van Kesteren, C, 2014)	0.4
" Compared with traditional dosing, this model-derived dosing regimen yields significantly reduced doses in neonates aged <10 days."	( Evidence-based morphine dosing for postoperative neonates and infants. Ceelie, I; Dahan, A; Danhof, M; de Wildt, SN; Knibbe, CA; Krekels, EH; Tibboel, D; van Dijk, M, 2014)	0.76
" The efficacy of this dosing algorithm was evaluated using morphine rescue medication and actual average infusion rates."	( Evidence-based morphine dosing for postoperative neonates and infants. Ceelie, I; Dahan, A; Danhof, M; de Wildt, SN; Knibbe, CA; Krekels, EH; Tibboel, D; van Dijk, M, 2014)	1
"Morphine paediatric dosing algorithms corrected for pharmacokinetic differences alone yield effective doses that prevent over-dosing for neonates with a PNA <10 days."	( Evidence-based morphine dosing for postoperative neonates and infants. Ceelie, I; Dahan, A; Danhof, M; de Wildt, SN; Knibbe, CA; Krekels, EH; Tibboel, D; van Dijk, M, 2014)	2.2
" Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen."	( Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats. Franklin, KB; Harvey-Lewis, C; Perdrizet, J, 2014)	0.7
"0625% bupivacaine + 2 μg/ml fentanyl + 2 mg morphine in 15 mL saline were given to Group bupivacaine-fentanyl-morphine (Group BFM) with no test dosing from the needle."	( Maternal and neonatal effects of adding morphine to low-dose bupivacaine for epidural labor analgesia. Ahiskalioglu, A; Aksoy, M; Alici, HA; Celik, M; Dostbil, A; Erdem, AF, )	0.66
" The risk of PE development increased with an increase in cumulative dosage and in the average dosage of morphine."	( Pulmonary embolism is associated with current morphine treatment in patients with deep vein thrombosis. Kao, CH; Lee, CW; Liang, JA; Muo, CH; Sung, FC; Yeh, JJ, 2015)	0.89
" The risk of ACS increased significantly with increasing morphine dosage (to ≥65 mg/y)."	( Modest increase in risk of acute coronary syndrome associated with morphine use in cancer patients: a population-based nested case-control study. Kao, CH; Lee, CW; Liang, JA; Muo, CH; Sung, FC, 2014)	0.88
" For constipation, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, morphine produced a bell-shaped dose-response curve, whereas DPDPE and U69,593 were inactive."	( In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile. Kuo, A; Meutermans, W; Smith, MT; Wyse, BD, 2015)	0.63
" For both experiments, cumulative morphine anti-nociceptive dose-response (ED50) was tested and hyperactive behaviors such as jumping and scratching were recorded."	( Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury. Chen, L; Mao, J; Martyn, JA; Song, L; Wang, S; Zuo, Y, 2014)	1
" The specific dosage of 100 nM produced additional marked reduction in activity for planaria exposed to either morphine or naloxone while only 1 pM of morphine produced this effect."	( Comparisons of responses by planarian to micromolar to attomolar dosages of morphine or naloxone and/or weak pulsed magnetic fields: revealing receptor subtype affinities and non-specific effects. Murugan, NJ; Persinger, MA, 2014)	0.84
" The objective of this study was to observe whether the dosing time of 6 narcotic analgesics in mice affected their efficacy, pain tolerance and recovery of tolerance."	( Chronopharmacology of analgesic effect and tolerance induced by six narcotic analgesics in mice. Chang, MJ; Jin, JJ; Li, XP; Liu, D; Luo, L; Xu, YJ; Yu, ZQ; Zhang, CL, 2015)	0.42
" In 82%, the dosage was not or only gradually increased during the last 3 days of life."	( [Frequency and characteristics of use of morphine at the end of life: a cross-sectional study]. Geijteman, E; Onwuteaka-Philipsen, BD; van Delden, JJ; van der Heide, A; van der Maas, PM; van Zuylen, L, 2014)	0.67
"We used the cheek model of itch and pain in rats to determine the dose-response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior."	( Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats. Giesler, GJ; Moser, HR, 2014)	0.63
" Administration of pioglitazone also prevented morphine-induced 50 % effective dose (ED50) shift to the right in the dose-response curve and increased the global analgesic effect of morphine."	( Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats. Azarfardian, A; Charkhpour, M; Ghasami, S; Ghavimi, H; Hassanzadeh, K; Maleki-Dizaji, N; Zolali, E, 2014)	0.97
" During the dosing period, the individual plasma ETP concentrations decreased at every dose."	( Pharmacokinetics and toxicity of repeated oral etoposide is altered by morphine coadministration in rats. Iwanaga, K; Kakemi, M; Kawase, T; Kitamura, T; Miyazaki, M; Nishimura, C, 2015)	0.65
" Our objective was to evaluate the impact of CPOE implementation on analgesic prescribing and dosing practices for renal colic presentations."	( Computerized physician order entry and decision support improves ED analgesic ordering for renal colic. Lang, E; Lonergan, K; McRae, A; Netherton, SJ; Wang, D, 2014)	0.4
" Morphine was required by only two patients per group (no difference in dosage or frequency)."	( Is single incision pediatric endoscopic surgery more painful than standard laparoscopy in children? Personal experience and review of the literature. Ade-Ajayi, N; Cancelliere, LA; Desai, AP; Kemal, KI; Patel, S; Zani, A, 2015)	1.33
" Increased dosing might result in a ceiling effect, and thus less analgesia than expected."	( Nalbuphine for postoperative pain treatment in children. Pogatzki-Zahn, E; Reichl, SU; Schnabel, A; Zahn, PK, 2014)	0.4
" The objective of this study was to identify predictors of increased opioid dosage in the last week of a terminal cancer patient's life."	( Dyspnea, relative youth and low daily doses of opioids predict increased opioid dosage in the last week of a terminal cancer patient's life. Abe, K; Hasuo, H; Kinoshita, H; Matsumoto, Y; Miura, T; Motonaga, S, 2014)	0.4
" We assigned the patients to increased group or decreased group according to changes in oral morphine equivalent dosage in their last 7 days."	( Dyspnea, relative youth and low daily doses of opioids predict increased opioid dosage in the last week of a terminal cancer patient's life. Abe, K; Hasuo, H; Kinoshita, H; Matsumoto, Y; Miura, T; Motonaga, S, 2014)	0.62
" Independent predictors of increased oral morphine equivalent dosage included dyspnea (odds ratio: 11."	( Dyspnea, relative youth and low daily doses of opioids predict increased opioid dosage in the last week of a terminal cancer patient's life. Abe, K; Hasuo, H; Kinoshita, H; Matsumoto, Y; Miura, T; Motonaga, S, 2014)	0.67
"Dyspnea, relative youth and oral morphine equivalent dosage <50 mg on Day 7 before death were predictive of increased oral morphine equivalent dosage in the last 7 days."	( Dyspnea, relative youth and low daily doses of opioids predict increased opioid dosage in the last week of a terminal cancer patient's life. Abe, K; Hasuo, H; Kinoshita, H; Matsumoto, Y; Miura, T; Motonaga, S, 2014)	0.68
" This prospective observational study examined the predictability of the patients' survival by variations of daily opioid dosage during the last few days of life."	( Prediction of patient survival by change in daily opioid dosage in advanced cancer patients: a prospective hospital-based epidemiologic study. Chiang, JK; Kao, YH, 2014)	0.4
" However, repeated or continuous use of morphine and other opioids are associated with a potential risk of analgesic tolerance, which requires an increase in dosage to maintain the same efficacy."	( [Easing human pain: challenges to a novel therapeutic drug in neuropathic pain]. Takano, Y, 2014)	0.67
" Repeated morphine injections alone led to a significant rightward shift in the morphine dose-response curve compared with that with A-317491."	( Blockade and reversal of spinal morphine tolerance by P2X3 receptor antagonist. Jiang, W; Ma, X; Xu, H; Xu, T, 2015)	1.1
" However, clinicians have long appreciated the ability to manage cancer pain in patients for months on stable opioid doses, implying that extended dosing may eventually result in a steady state in which the degree of tolerance remains constant despite the continued administration of a fixed morphine dose."	( Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs. Faskowitz, AJ; Lu, Z; Pan, YX; Pasternak, GW; Rossi, GC; Xu, J; Xu, M, 2015)	0.93
"The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate."	( Pharmacokinetic correlates of the effects of a heroin vaccine on heroin self-administration in rats. LeSage, MG; Pentel, PR; Raleigh, MD, 2014)	0.65
" Our study suggests that pharmacogenetics for personalized dosing might be most effectively advanced by studying the interplay between pharmacogenetics, population pharmacokinetics, and clinical pharmacokinetics."	( CYP2D6 phenotype-specific codeine population pharmacokinetics. Boston, RC; Daly Linares, AL; Fudin, J; Linares, OA; Schiesser, WE, 2015)	0.42
" During the same period, narcotic analgesic dosage requirement was cut down by 20% in the study group (average of 29."	( Scheduled intravenous acetaminophen reduces postoperative narcotic analgesic demand and requirement after laparoscopic Roux-en-Y gastric bypass. Jose, P; Nau, P; Pedersen, M; Samuel, I; Saurabh, S; Smith, JK, )	0.13
"To evaluate the association between opioid dosage and ongoing therapy with physical function and disability in patients with neuropathic pain (NeP)."	( Physical Functioning and Opioid use in Patients with Neuropathic Pain. Bostick, GP; Carr, EC; Clark, AJ; Gordon, A; Lynch, M; Morley-Forster, P; Moulin, DE; Nathan, H; Smyth, C; Stitt, LW; Toth, C; Ware, MA, 2015)	0.42
"03), but was not significant until 120 min after dosing and did not correlate to the increase in tolerated muscle pressure (r = -0."	( Objective markers of the analgesic response to morphine in experimental pain research. Brokjær, A; Christrup, LL; Dahan, A; Drewes, AM; Gram, M; Graversen, C; Kreilgaard, M; Olesen, AE, )	0.39
" Various dosage of Curcumin attenuated these effects by significantly lowering lipid peroxidation, GSSG level, Bax concentration, caspase-3 and caspase-9 activities, while increasing superoxide dismutase and glutathione peroxidase activity, GSH level and Bcl-2 concentration."	( Protective effects of various dosage of Curcumin against morphine induced apoptosis and oxidative stress in rat isolated hippocampus. Fatima, S; Karimian, M; Motaghinejad, M; Motaghinejad, O; Shabab, B; Yazdani, I, 2015)	0.66
"Chromatographic purity profiling (CPP) is the common name of a group of analytical and chemometric applications for detection, identification and quantitative determination of related substances and other impurities in active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs)."	( Fingerprinting of morphine using chromatographic purity profiling and multivariate data analysis. Acevska, J; Cho, J; Cvetkovikj, I; Dimitrovska, A; Kulevanova, S; Petkovska, R; Stefkov, G, 2015)	0.75
" Brain exposure at microdosing agreed with pharmacological dosing conditions for the investigated drugs."	( Large Variation in Brain Exposure of Reference CNS Drugs: a PET Study in Nonhuman Primates. Amini, N; Farde, L; Finnema, SJ; Halldin, C; Lundquist, S; Nakao, R; Schou, M; Takano, A; Varnäs, K, 2015)	0.42
" As long as morphine did not cause reduced participation due to sedation, subcutaneous morphine dosing reduced the effects of capsaicin (p<0."	( A novel operant-based behavioral assay of mechanical allodynia in the orofacial region of rats. Allen, KD; Caudle, RM; Jacobs, BY; Kloefkorn, HE; Lakes, EH; Neubert, JK; Rohrs, EL, 2015)	0.8
" Thus, varying the dosage regimen of morphine can reduce the severity of morphine-induced dependency and neurodegeneration."	( The effect of various morphine weaning regimens on the sequelae of opioid tolerance involving physical dependency, anxiety and hippocampus cell neurodegeneration in rats. Asadighaleni, M; Fatima, S; Karimian, SM; Motaghinejad, M; Motaghinejad, O; Shabab, B, 2015)	1
"Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians."	( A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain. Christrup, LL; Drewes, AM; Kreilgaard, M; Lund, TM; Olesen, AE; Sverrisdóttir, E, 2015)	2.24
", administration route, average dosage and number of consumers) contribute to depict a realistic representation of the phenomenon in the investigated area."	( Data triangulation in the context of opioids monitoring via wastewater analyses. Been, F; Benaglia, L; Delémont, O; Esseiva, P; Gervasoni, JP; Lucia, S, 2015)	0.42
" To constitute morphine tolerance, we used a 3 day cumulative dosing regimen."	( Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. Altun, A; Bagcivan, I; Durmus, N; Gursoy, S; Ozdemir, E; Yildirim, K, 2015)	1.12
" Mean daily morphine equivalent dosing decreased from 805."	( Prospective Observational Study of Patient-Controlled Intrathecal Analgesia: Impact on Cancer-Associated Symptoms, Breakthrough Pain Control, and Patient Satisfaction. Brogan, SE; Okifuji, A; Winter, NB, )	0.51
" These findings support other clinical research failing to show dose-response relationships for growth and bone outcomes among intrauterine TFV-exposed infants."	( Meconium Tenofovir Concentrations and Growth and Bone Outcomes in Prenatally Tenofovir Exposed HIV-Uninfected Children. Hazra, R; Himes, SK; Huestis, MA; Jacobson, DL; Kacanek, D; Rich, KC; Siberry, GK; Tassiopoulos, K; Van Dyke, RB; Wu, JW, 2015)	0.42
" Although guidelines and protocols relating to the dosage and administration of morphine exist, little data are available describing its use by South African paramedics."	( Use of morphine sulphate by South African paramedics for prehospital pain management. de Kock, JM; Vincent-Lambert, C, )	0.81
" The administration of simvastatin also prevented the morphine-induced shift to the right of the 50% effective dose (ED50) in the dose-response curve."	( Simvastatin prevents morphine antinociceptive tolerance and withdrawal symptoms in rats. Ghasemi, F; Hassanzadeh, K; Izadpanah, E; Moloudi, MR; Moradi, A; Rahimmi, A, 2015)	0.98
" Caverage, calculated within the first hour of dosing of acetaminophen (average concentration at 0-1 hour, C0-1havg), can be used as a key surrogate to distinguish the effects of gastric emptying on the absorption of acetaminophen."	( Acetaminophen absorption kinetics in altered gastric emptying: establishing a relevant pharmacokinetic surrogate using published data. Srinivas, NR, 2015)	0.42
" dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone."	( Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat. Angus, JA; Tung, KH; Wright, CE, 2015)	0.66
" Patient demographics and opioid dosing information were extracted from an electronic medical record."	( Variable Patterns of Continuous Morphine Infusions at End of Life. Atayee, RS; Ching, A; Edmonds, KP; Lin, KJ; Ma, JD; Revta, C; Roeland, EJ, 2015)	0.7
" These findings will help clinicians to find the most adequate and safe analgesic dosing regimens for neonates and infants."	( Long-Term Effects of Neonatal Morphine Infusion on Pain Sensitivity: Follow-Up of a Randomized Controlled Trial. de Graaf, J; Groot Jebbink, LJ; Tibboel, D; Valkenburg, AJ; van den Bosch, GE; van Dijk, M; van Lingen, RA; van Rosmalen, J; Weisglas-Kuperus, N, 2015)	0.71
" Morphine dosage was calculated as the cumulative dose administered during the neonatal intensive care unit period."	( Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. Aikio, O; Hallman, M; Härmä, A; Saarela, T, 2016)	1.6
" Future pharmacodynamic investigations are needed to identify target concentrations in this population, after which final dosing recommendations can be made."	( Morphine Glucuronidation and Elimination in Intensive Care Patients: A Comparison with Healthy Volunteers. Ahlers, SJ; Dahan, A; Gulik, Lv; Knibbe, CA; Peeters, MY; Tibboel, D; Välitalo, PA; van Dongen, EP, 2015)	1.86
" To constitute morphine analgesic tolerance, a 3-day cumulative dosing regimen was used."	( The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Altun, A; Bagcivan, I; Durmus, N; Gursoy, S; Ozdemir, E; Yildirim, K, 2015)	0.77
" Further research is warranted to elucidate the optimal timing and dosing of IA ketamine and morphine for postoperative analgesic effects."	( Effect of preemptive intra-articular morphine and ketamine on pain after arthroscopic rotator cuff repair: a prospective, double-blind, randomized controlled study. Amar, E; Chechik, O; Dolkart, O; Khashan, M; Maman, E; Mozes, G; Sharfman, Z; Weinbroum, A, 2016)	0.93
" The dosage of morphine was counted as defined daily dose and its effect was assessed by multivariable Cox proportional hazard regression controlling age, Charlson comorbidity index, outpatient department visits, antipsychotics, and breast cancer drugs."	( Risk of type 2 diabetes mellitus in female breast cancer patients treated with morphine: A retrospective population-based time-dependent cohort study. Chang, YJ; Lai, SW; Lee, CW; Morisky, DE; Muo, CH; Wang, IK; Yang, SP, 2015)	1
" The results showed that a single injection of morphine could induce behavioral sensitization by a low challenge dosage of morphine after a 7-days drug free period."	( The α1 adrenoceptors in ventrolateral orbital cortex contribute to the expression of morphine-induced behavioral sensitization in rats. Gao, HY; Huo, FQ; Li, T; Liang, F; Wei, L; Yan, CX; Zhang, YX; Zhu, YM, 2016)	0.92
" Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship."	( Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials. Cheng, D; Johnston, B; Kaushal, A; Martin, J; Wang, L; Zhu, F, 2016)	0.77
" Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen."	( Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring. Byrnes, EM; Vassoler, FM; Wright, SJ, 2016)	0.9
"Morphine dosing can be challenging in terminally ill adult patients due to the heterogeneous nature of the population and the difficulty of accurately assessing pain during sedation."	( Pharmacokinetics of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Terminally Ill Adult Patients. Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Masman, AD; Mathot, RA; Tibboel, D; van Gelder, T, 2016)	2.2
" Nociceptive behaviours and cumulative dose-response of morphine analgesia were assessed."	( Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats. Couture, R; Hong, Y; Huang, J; Li, Q; Wang, D; Zeng, J, 2016)	0.88
"The protocols varied widely in terms of medication and dosing choices, as well as listed contraindications to treatments."	( Chest Pain of Suspected Cardiac Origin: Current Evidence-based Recommendations for Prehospital Care. Barger, JA; Brown, JF; Gilbert, GH; Koenig, KL; Rudnick, EM; Salvucci, AA; Savino, PB; Sporer, KA, 2015)	0.42
" Opioids were not dosed in an equipotent manner."	( The Changing Use of Intravenous Opioids in an Emergency Department. Albertson, TE; Chenoweth, JA; Clarke, SO; Gutierrez, R; Roche, BM; Sutter, ME; Wintemute, GJ, 2015)	0.42
" The JCAHO program likely was at least indirectly responsible for this change in relative dosing of the opioids."	( The Changing Use of Intravenous Opioids in an Emergency Department. Albertson, TE; Chenoweth, JA; Clarke, SO; Gutierrez, R; Roche, BM; Sutter, ME; Wintemute, GJ, 2015)	0.42
" Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h."	( Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics. Cape, G; Devane, J; Friedhoff, L; Glue, P; Gray, A; Harland, S; Howes, J; Hung, CT; Hung, N; Lam, F; Lockhart, M; Tunnicliff, D; Weis, H, 2016)	0.91
"This study developed a stability-indicating reversed-phase HPLC method for the simultaneous determination of morphine sulfate and naltrexone hydrochloride content in bulk, Solid dosage forms and in-vitro dissolution samples to support product development and quality control efforts."	( A stability-indicating HPLC method for simultaneous determination of morphine and naltrexone. Barzin, J; Jafari-Nodoushan, M; Mobedi, H, 2016)	0.88
"Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow some withdrawal during each dosing interval, which causes repeated stress."	( Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Allahverdiyev, O; Enginar, N; Nurten, A; Sehirli, I; Türkmen, AZ, 2015)	0.93
"Male and female rats and mice were administered with increasing doses of morphine twice daily at different dosing intervals."	( Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Allahverdiyev, O; Enginar, N; Nurten, A; Sehirli, I; Türkmen, AZ, 2015)	0.92
"Male rats and male and female rats displayed manifestations of morphine withdrawal at the end of 14-h and 24-h dosing intervals, respectively."	( Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Allahverdiyev, O; Enginar, N; Nurten, A; Sehirli, I; Türkmen, AZ, 2015)	0.93
" Median of morphine dosage was equal between two groups on postoperative 4 h, 1 d, 2 d, cumulative amount of morphine of cryoanalgesia group was higher than intravenous group, but the difference between the two groups was not statistically significant."	( [Analgesic effect and safety of intercostal nerve cryoanalgesia after the video-assisted thoracoscopic surgery]. He, Y; Li, F; Li, W; Li, Y; Lin, H; Wang, J; Xu, M; Ye, S, 2015)	0.81
"These findings may have important implications in patients with low-grade inflammation and imply the need to modify morphine dosing regimens to ensure optimal analgesia."	( Effects of Low-Dose Escherichia coli Lipopolysaccharide-Induced Endotoxemia on Morphine Pharmacokinetics in an Animal Model. Billert, H; Grabowski, T; Grześkowiak, E; Lisiecka, J; Michalak, M; Szkutnik-Fiedler, D; Urjasz, H, 2016)	0.87
"First, a dose-response curve for analgesic efficacy was generated for each opioid agonist."	( Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury. Aceves, M; Hook, MA; Mathai, BB, 2016)	0.43
" To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines."	( Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol. Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Mathôt, RA; Tibboel, D; van Esch, HJ; van Gelder, T; van Zuylen, L, 2016)	0.66
"We used the intestinal segregated flow model (SFM) versus the traditional model (TM), nested within physiologically based pharmacokinetic (PBPK) models, to describe the biliary and urinary excretion of morphine 3β-glucuronide (MG) after intravenous and intraduodenal dosing of morphine in rats in vivo."	( Metabolite Kinetics: The Segregated Flow Model for Intestinal and Whole Body Physiologically Based Pharmacokinetic Modeling to Describe Intestinal and Hepatic Glucuronidation of Morphine in Rats In Vivo. Chen, S; Fan, J; Liu, L; Pang, KS; Sun, H; Yang, QJ, 2016)	0.81
" Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation."	( Oral morphine for cancer pain. Moore, RA; Wee, B; Wiffen, PJ, 2016)	1.24
" Analysis was based on 748 Numerical Rating Scale (NRS) scores of pain intensity and 51 observed morphine and oxycodone dosing events."	( A Model-Based Approach for Joint Analysis of Pain Intensity and Opioid Consumption in Postoperative Pain. Christrup, LL; Drewes, AM; Juul, RV; Knøsgaard, KR; Kreilgaard, M; Lund, TM; Olesen, AE; Osther, PJ; Pedersen, KV, 2016)	0.65
"Preoperatively, 95% of the patients received morphine versus 100% postoperatively, with a median dosage of 10."	( Infants Operated on for Necrotizing Enterocolitis: Towards Evidence-Based Pain Guidelines. Keyzer-Dekker, CM; Knibbe, CA; Meesters, NJ; Simons, SH; Tibboel, D; van Dijk, M, 2016)	0.69
" However, pharmacokinetic data to support morphine dosing in this vulnerable population are lacking."	( Decreased Morphine Clearance in Neonates With Hypoxic Ischemic Encephalopathy Receiving Hypothermia. Bonifacio, SL; Drover, DR; Frymoyer, A; Su, F; Van Meurs, KP; Wustoff, CJ, 2017)	1.12
" The injection dosage of dexmedetomidine and morphine hydrochloride, analgesia satisfaction rate, sedation satisfaction rate, the incidences of adverse reactions during treatment such as bradycardia and low blood pressure, mechanical ventilation time, ICU time, and hospitalization expense were observed and recorded in the two groups."	( [Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery]. Cao, WZ; Xu, SA; Xu, XQ; Yu, HJ, 2016)	0.69
"The analgesia method of ACM could reduce the dosage of traditional analgesic drugs and the occurrence of partial adverse reactions."	( [Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery]. Cao, WZ; Xu, SA; Xu, XQ; Yu, HJ, 2016)	0.43
" There was no difference in morphine dosage for both groups."	( Effect of music intervention on burn patients' pain and anxiety during dressing changes. Chen, LF; Hsiep, PH; Hsu, KC, 2016)	0.73
"A low dosage of intrathecal morphine is safe and effective after minimally invasive lumbar fusion surgery."	( Intrathecal Versus Intravenous Morphine in Minimally Invasive Posterior Lumbar Fusion: A Blinded Randomized Comparative Prospective Study. Araimo Morselli, FSM; Caporlingua, A; Caporlingua, F; De Biase, L; Imperiale, C; Scarpa, I; Tordiglione, P; Zuccarini, F, 2017)	1.04
"180 male rats were randomly divided into nine groups, 20 rats for each group: saline group (N), model group (M), NS treatment group and three different dosage of Corydalis yanhusuo and L-THP groups (low dose group,middle dose group and high dose group)."	( [Effect of Corydalis yanhusuo and L-THP on Gastrointestinal Dopamine System in Morphine-Dependent Rats]. Bai, WF; Luo, SY; Qiu, CK; Tu, P; Xu, JY; Yu, SY, 2015)	0.64
" Moreover, thalidomide prevented the morphine-induced shift to the right of the ED50 in the dose-response curve."	( A new pharmacological role for thalidomide: Attenuation of morphine-induced tolerance in rats. Amini, H; Hassanzadeh, K; Izadpanah, E; Khodadadi, B; Moloudi, MR; Rahmani, MR, 2016)	0.95
" We have no evidence to adjust morphine dosing after cardiac surgery in children with Down syndrome."	( Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in Children With and Without Down Syndrome. Breatnach, CV; Calvier, EA; Casey, WF; Knibbe, CA; Krekels, EH; Mathôt, RA; O'Hare, BP; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2016)	0.99
" The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied."	( Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain. Barratt, DT; Coller, JK; Hutchinson, MR; Sia, AT; Somogyi, AA; Tan, EC, 2016)	0.87
" This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain."	( Dose and Duration of Opioid Use in Patients with Cancer and Noncancer Pain at an Outpatient Hospital Setting in Malaysia. Choy, LW; Ismail, CR; Rahman, NA; Zin, CS, 2017)	0.46
"The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50μg produces analgesia similar to that produced by either 100μg or 150μg."	( Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial. Alshaeri, T; Amdur, RL; Berger, JS; Gonzalez, A; Hopkins, A; Jeon, D; Smiley, R; Wang, S, 2016)	0.98
" WT mice received several dosing regimens of morphine."	( Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model. Arias, RS; Brown, RH; Dalesio, NM; Galinkin, J; Hendrix, CW; Lee, CK; Lynn, RR; McMichael, DH; Pho, H; Schwartz, AR; Thompson, CB; Yaster, M, 2016)	0.96
" These results suggest that the reward-related behavioral effects of morphine are overall not robustly altered by the presence of paclitaxel treatment under the current dosing regimen, with the exception of maintaining a small yet significant higher baseline than saline treatment during the development of allodynia in male mice."	( Effects of paclitaxel on mechanical sensitivity and morphine reward in male and female C57Bl6 mice. Neelakantan, H; Walker, EA; Ward, SJ, 2016)	0.92
"Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes."	( Deficits in autonomic indices of emotion regulation and reward processing associated with prescription opioid use and misuse. Bryan, CJ; Froeliger, B; Garland, EL; Howard, MO; Nakamura, Y, 2017)	0.46
" The median dosage of opioids was 13."	( A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids. Awa, H; Chihara, T; Futamura, A; Higashiguchi, T; Ito, A; Mori, N; Murai, M; Ohara, H; Uekuzu, Y, 2017)	0.46
" Moreover, differences in morphine dose-response in the two components of pain have not been examined in male and female rats."	( Dissociation of morphine analgesic effects in the sensory and affective components of formalin-induced spontaneous pain in male and female rats. Armendariz, A; Harton, LR; Nazarian, A; Richardson, JR, 2017)	1.1
"Burn victim patients are frequently prescribed opioids at doses that are significantly higher than standard analgesic dosing guidelines, and, even despite an escalation in opioid dosing, many continue to experience pain."	( Burn injury decreases the antinociceptive effects of opioids. Bates, MLS; Eitan, S; Emery, MA; Wellman, PJ, 2017)	0.46
" With the dosing used in our study, analgesia from morphine lasted longer than hydromorphone via intrathecal and epidural routes; however, neuraxial hydromorphone remains a reasonable option for long-acting analgesia post cesarean delivery."	( Neuraxial opioids for post-cesarean delivery analgesia: can hydromorphone replace morphine? A retrospective study. Balofsky, A; Edwards, K; Feng, C; Iqbal, A; Jackson, M; Kanel, J; Marroquin, B; Newton, M; Rothstein, D; Wissler, R; Wong, E, 2017)	0.93
"The addition of intradural morphine allows a reduction in the dosage of local anesthetic improves short-term postoperative analgesia and is associated with less motor blockade."	( Intraspinal administration of morphine hydrochloride combined with low doses of bupivacaine in hemorrhoidectomy: a clinical randomized trial. de Abajo Iglesias, FJ; Rodríguez-Miguel, A; Ruiz-Castro, M; San José Santos, M, 2017)	1.04
" In this review, we provide an overview on dosing regimens of morphine currently reported to treat NAS, with the aim to stimulate discussion on the need for a standardized dosing through better study design."	( Morphine treatment for neonatal abstinence syndrome: huge dosing variability underscores the need for a better clinical study design. Allegaert, K; Mian, P; Tibboel, D; van den Anker, JN; Wildschut, ED, 2019)	2.2
"A search strategy was performed in PubMed to identify studies that provide a dosing regimen used, or advised by a review or guideline for morphine to treat NAS."	( Morphine treatment for neonatal abstinence syndrome: huge dosing variability underscores the need for a better clinical study design. Allegaert, K; Mian, P; Tibboel, D; van den Anker, JN; Wildschut, ED, 2019)	2.16
" Extensive variability was observed for dosing advice, threshold in the initiating phase, dosing advice and maximum dose in the escalating phase."	( Morphine treatment for neonatal abstinence syndrome: huge dosing variability underscores the need for a better clinical study design. Allegaert, K; Mian, P; Tibboel, D; van den Anker, JN; Wildschut, ED, 2019)	1.96
"This review shows a large variability in dosing regimens of morphine used to treat NAS."	( Morphine treatment for neonatal abstinence syndrome: huge dosing variability underscores the need for a better clinical study design. Allegaert, K; Mian, P; Tibboel, D; van den Anker, JN; Wildschut, ED, 2019)	2.2
" Especially lacking are in-depth studies about its mechanisms of action, receptor pharmacology, dose-response relationships and clinical dosing regimens."	( [Piritramide : A critical review]. Bantel, C; Hinrichs, M; Weyland, A, 2017)	0.46
" Morphine dosage administered, and severity of pain monitoring was accessed and recorded with a visual analogue scale (VAS)."	( Magnesium Sulfate Mediates Morphine Administration Reduction in Varicocelectomy Surgery. Mahmoudvand, H; Moradkhani, MR; Nadri, S, 2018)	1.69
" This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects."	( Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl. Hall, C; Hotham, E; Lloyd, RA; Suppiah, V; Williams, M, 2017)	0.67
" This is especially important in the case of pediatric patients, and dose-response relationships require studies using pharmacokinetic-pharmacodynamic modeling."	( A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive. Aro, R; Herodes, K; Kipper, K; Lutsar, I; Metsvaht, T; Standing, JF; Veigure, R, 2017)	0.68
" Despite increased mechanistic understanding of morphine tolerance, little is known about the influence of dosing regimens in its development."	( Morphine dosing strategy plays a key role in the generation and duration of the produced antinociceptive tolerance. Dietis, N; Gueven, N; Paul, AK, 2017)	2.15
"Improved intrathecal (IT) pump technology is increasing the accuracy of IT opioid bolus dosing and promising advances in pain therapy."	( Reinstituting the Bolus - New Reasoning for an Existing Technique. Apostol, C; McRoberts, PW; Pope, JE, 2017)	0.46
" The aim of this study was to determine the effect of dosing time on the pharmacokinetics and brain distribution of morphine."	( Diurnal variation in the pharmacokinetics and brain distribution of morphine and its major metabolite. de Lange, ECM; Hartman, R; Kervezee, L; Meijer, JH; van den Berg, DJ, 2017)	0.9
" Data were reviewed and compared between the two protocol groups to determine the impact that the dosage change had on length of hospital stay and morphine treatment duration."	( Evaluation of the Effectiveness of Two Morphine Protocols to Treat Neonatal Abstinence Syndrome in a Level II Nursery in a Community Hospital. Burton, A; DeAtley, HN; Fraley, MD; Haltom, J, 2017)	0.92
" Furthermore, dose-response revealed that IRR rats were more sensitive at a lower dose."	( Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization. Bulin, SE; Eisch, AJ; Mendoza, ML; Richardson, DR; Solberg, TD; Song, KH; Yun, S, 2018)	0.72
" Pain was assessed with a visual analog scale (VAS), 48-h morphine consumption and 72-h local anesthetic dosage were recorded, motor blockade was assessed, maximum range of motion (ROM) was measured, and adverse effect profiles were recorded."	( Comparison of 2 Analgesia Modalities in Total Knee Replacement Surgery: Is There an Effect on Knee Function Rehabilitation? Gelmanas, A; Macas, A; Mockutė, L; Tamošiūnas, R; Vertelis, A; Zinkus, J, 2017)	0.7
" However, opioid dosage did not affect overall survival."	( Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes. Eom, W; Jeon, JH; Kim, JH; Kim, MS; Kim, SE; Lee, JM; Lim, H; Oh, TK, 2017)	0.46
" Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test."	( An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac. Abotsi, WKM; Agyare, C; Ameyaw, EO; Biney, RP; Boakye-Gyasi, E; Kasanga, EA; Woode, E, 2018)	0.92
"Pain was not better controlled with the addition of continuous infusions of morphine and midazolam when compared with intermittent dosing only."	( Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial. Brady, CM; Lefaiver, CA; Penk, JS; Steffensen, CM; Wittmayer, K, 2018)	0.71
" Confirmed by the cubic interpolation planes, the dose-response data revealed a cross-state-dependent learning between morphine and nicotine which may be mediated by the CeA endocannabinoid system via CB1 receptors."	( Interactive effects of morphine and nicotine on memory function depend on the central amygdala cannabinoid CB1 receptor function in rats. Alijanpour, S; Rezayof, A; Tirgar, F; Yazdanbakhsh, N, 2018)	1
" The approved dosage strengths of morphine-ADER-IMT are bioequivalent to corresponding dosage strengths of morphine ER (MS Contin®; Purdue Pharma LP, Stamford, CT)."	( Abuse-deterrent features of an extended-release morphine drug product developed using a novel injection-molding technology for oral drug delivery. Dayno, JM; Elhauge, T; Lindhardt, K; Skak, N, )	0.67
" Because these offspring are more sensitive to the analgesic effect of morphine, clinicians should consider this issue to manage the dosage of morphine for treating pain in children with an abstinent parent(s)."	( Is the Nociception Mechanism Altered in Offspring of Morphine-Abstinent Rats? Akbarabadi, A; Ashabi, G; Khalifeh, S; Kheiri, Z; Sadat-Shirazi, MS; Toolee, H; Vousooghi, N; Zarrindast, MR, 2018)	0.96
"Drug dosing in infants frequently depends on body weight as a crude indicator for maturation."	( Drug metabolism in early infancy: opioids as an illustration. Allegaert, K; Mian, P; Tibboel, D; Van Den Anker, J; Van Donge, T, 2018)	0.48
" However, the low number of studies and variation in dosing regimens limits the evidence for its use."	( Preoperative intravenous glucocorticoids can decrease acute pain and postoperative nausea and vomiting after total hip arthroplasty: A PRISMA-compliant meta-analysis. Li, A; Xin, W; Yang, Q; Zhang, Z, 2017)	0.46
" A 6-day continuous dosing of morphine from osmotic minipumps was used to establish morphine tolerance in female rats."	( Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels. Arkwright, NB; Davis, TP; Hunn, KC; Jacobs, LM; Jarvis, CK; Largent-Milnes, TM; Schaefer, CP; Tome, ME, 2018)	1.2
" This model will allow optimization of dosing strategies in future clinical trials."	( The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome. Adeniyi-Jones, SC; Ehrlich, ME; Fang, WB; Gastonguay, MR; Kraft, WK; Moody, DE; Moore, JN; Ng, CM, 2018)	0.48
" Morphine bolus dosing was used as needed, and total dose was tracked."	( Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery. Bourne, DWA; Christians, U; da Cruz, EM; Galinkin, J; Goot, BH; Hickey, F; Kaufman, J; Pan, Z; Twite, M; Zuk, J, 2018)	2.83
"In current clinical practice, morphine is dosed in older patients based on patient-weight, with different calculations for adjustment."	( Age-dependent antinociception and behavioral inhibition by morphine. Dietis, N; Gueven, N; Paul, AK, 2018)	1.01
" Gabapentin dosing was 600 mg (<65 years) or 300 mg (>65 years)."	( Does low-dose gapapentin reduce opioid use postoperatively?: A randomized controlled trial in women undergoing reconstructive pelvic surgery. Alarab, M; Dawood, A; Lemos, N; Li, ALK; Lovatsis, D; McDermott, CD; Siddiqui, NT; Wadsworth, K, 2019)	0.51
"The purpose of this systematic review is to describe the effect of preoperative intrathecal morphine (ITM) on postoperative intravenous (IV) morphine dosage during the first postoperative day."	( Effects of preoperative intrathecal morphine on postoperative intravenous morphine dosage: a systematic review protocol. Garbee, D; Pitre, L; Pitt, A; Schiavo, J; Tipton, J, 2018)	0.98
" There are advantages and disadvantages in using these 2 opioids which are discussed, and potential dosing strategies are outlined."	( What Parenteral Opioids to Use in Face of Shortages of Morphine, Hydromorphone, and Fentanyl. Behm, B; Davis, MP; Fernandez, C; McPherson, ML; Mehta, Z, 2018)	0.73
" The efficacy of miR-124 and miR-146a were comparable, and in both cases allodynia returned within hours to days of miRNA dosing conclusion."	( MicroRNA-124 and microRNA-146a both attenuate persistent neuropathic pain induced by morphine in male rats. Galer, EL; Grace, PM; Maier, SF; Strand, KA; Watkins, LR, 2018)	0.7
" In total, 36,000 simulated human subjects (100 per modelled group of different ages and gender) received repeated simulated morphine dosing with modified-release or immediate-release formulations."	( In silico (computed) modelling of doses and dosing regimens associated with morphine levels above international legal driving limits. Berry, DJ; Boland, JW; Ferreira, D; Johnson, M, 2018)	0.92
"Correlations between patient survival, initial opioid dose, final opioid dose, and the rate of increase of opioid dosage could provide useful information for clinicians treating unresectable pancreatic cancer patients."	( Association Between Opioid Use and Survival Time in Patients With Unresectable Pancreatic Cancer: 10 Years of Clinical Experience. Do, SH; Oh, TK; Song, IA; Yoon, YS, 2018)	0.48
"5 hours before dosing and 12 hours after dosing, all subjects received a 50-mg oral naltrexone tablet to minimize opioid-related side effects."	( Relative Oral Bioavailability of an Abuse-deterrent, Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period, Single-dose, Randomized Crossover Study in Healthy Subjects. Aigner, S; Kinzler, ER; Pantaleon, C, 2018)	0.7
" We hypothesized that there would be (1) direct relationship between dosing and side effects, and (2) an inverse relationship between ITM dosing and 24-hour postoperative opioid requirement."	( Safety and side-effect profile of intrathecal morphine in a diverse patient population undergoing total knee and hip arthroplasty. Golladay, GJ; Hess, SR; Jiranek, WA; Lahaye, LA; Sima, AP; Waligora, AC, 2019)	0.77
" For both morphine and ziconotide, the PACC guidelines recommend conservative initial dosing strategies."	( Intrathecal Therapy for Chronic Pain: A Review of Morphine and Ziconotide as Firstline Options. Deer, TR; Hanes, MC; McDowell, GC; Pope, JE, 2019)	1.17
" All dosing data were converted to oral morphine equivalents (OMEs)."	( Too much of a bad thing: Discharge opioid prescriptions in pediatric appendectomy patients. Anderson, KT; Austin, MT; Bartz-Kurycki, MA; Ferguson, DM; Kao, LS; Kawaguchi, AL; Lally, KP; Tsao, K, 2018)	0.75
" Dose-response curves for morphine, maraviroc (a CCR5 antagonist), and AMD3100 (a CXCR4 antagonist) alone were established."	( Coadministration of Chemokine Receptor Antagonists with Morphine Potentiates Morphine's Analgesic Effect on Incisional Pain in Rats. Adler, MW; Chen, X; Cowan, A; Doura, M; Eisenstein, TK; Geller, EB; Inan, S; Meissler, JJ; Rawls, SM; Tallarida, CS; Watson, MN, 2018)	1.03
" Discharge prescription in morphine milligram equivalents (MMEs, a standardized dosing unit that allows for comparison across opioid types) was calculated."	( Prescription Opioid Type and the Likelihood of Prolonged Opioid Use After Orthopaedic Surgery. Basilico, M; Bhashyam, AR; Harris, MB; Heng, M, 2019)	0.81
" TIRF use was mainly related to background opioid dosage and the patient's self-sufficiency in taking medication."	( Breakthrough cancer pain tailored treatment: which factors influence the medication choice? An observational, prospective and cross-sectional study in patients with terminal cancer. Calvieri, A; Casale, G; Dardeli, A; Eusepi, G; Giannarelli, D; Magnani, C; Mastroianni, C; Restuccia, MR, 2018)	0.48
"The present study involved segmental testing of hair in two clinical cases with known dosage histories."	( Segmental Hair Analysis-Interpretation of the Time of Drug Intake in Two Patients Undergoing Drug Treatment. Johansen, SS; Linnet, K; Nielsen, MKK; Wang, X, 2019)	0.51
" The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure."	( Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation. Chen, SH; Cheng, J; Li, Y; Li, YM; Pan, J; Shi, DL; Sun, J; Wang, Y; Zhang, HZ; Zhou, K, 2018)	0.48
" Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4."	( Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation. Chen, SH; Cheng, J; Li, Y; Li, YM; Pan, J; Shi, DL; Sun, J; Wang, Y; Zhang, HZ; Zhou, K, 2018)	0.71
"The administration of personalized dosage of morphine to HCC patients undergoing percutaneous MWA is an effective and safe procedure for pain control."	( Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation. Chen, SH; Cheng, J; Li, Y; Li, YM; Pan, J; Shi, DL; Sun, J; Wang, Y; Zhang, HZ; Zhou, K, 2018)	0.74
" The secondary outcomes included visual analog scale scores, time to first and total dosage of rescue analgesia, Timed Up and Go test, range of motion, muscle strength test, hospital stay, and patient satisfaction."	( Opioid-Sparing Analgesia and Enhanced Recovery After Total Knee Arthroplasty Using Combined Triple Nerve Blocks With Local Infiltration Analgesia. Amarase, C; Kampitak, W; Ngarmukos, S; Tanavalee, A, 2019)	0.51
" Because of its strong analgesic activity and dosage form, fentanyl has become one of the first choices for severe and moderate pain in clinical practice."	( Comparison of the use of different analgesics in the course of anesthesia care based on pharmacoeconomics. Jing, C; Ping, Y; Qing, J, 2018)	0.48
" Pharmacokinetics and optimal dosing of morphine in this population are largely unknown."	( Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia. Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Dudink, J; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019)	1.1
" There was a significant trend of increasing daily dosage with increased age; 36."	( Opioid Prescribing in the Pediatric Orthopaedic Trauma Population. Beuhler, M; Bosse, MJ; Gerkin, E; Gibbs, M; Griggs, C; Hsu, JR; Jarrett, S; Leas, D; LeFlore, MH; Runyon, M; Saha, A; Scannell, BP; Schiro, S; Seymour, RB; Simril, RT; Wally, MK; Watling, B; Wyatt, S, )	0.13
"Concentrations of morphine in PFS for N/PCA were identified that accommodated dosage variation across a 1-50 kg weight range."	( Standardised concentrations of morphine infusions for nurse/patient-controlled analgesia use in children. Davies, C; Forbes, B; Rashed, AN; Tomlin, S; Whittlesea, C, 2019)	1.13
" Wilcoxon non-paired signed rank test was used to examine the change in fentanyl dosage and IV:IT conversion ratio."	( Conversion of Intrathecal Opioids to Fentanyl in Chronic Pain Patients With Implantable Pain Pumps: A Retrospective Study. Kim, DD; Patel, A; Sibai, N, 2019)	0.51
" A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration."	( Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting. AbouNahia, F; Abushanab, D; Al-Badriyeh, D; Alsoukhni, O, 2019)	0.79
" It is a single-strength tablet housed in a single-dose applicator (which may minimize the likelihood of dosing errors) and is strictly for use in medically supervised/monitored settings."	( Sufentanil 30 µg Sublingual Tablet: A Review in Acute Pain. Deeks, ED, 2019)	0.51
" Secondarily, dosing of opioids and benzodiazepines was examined."	( The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study. Breatnach, CV; Cousins, G; Dawkins, I; Doherty, DR; Gallagher, PJ; Hayden, JC; Healy, M; Leacy, FP, 2019)	0.51
" A strong consensus was achieved regarding which pharmacological treatment (transmucosal fentanyl) and dosing method (start low and go slow) are the most suitable for the older population."	( Expert consensus on the management of breakthrough cancer pain in older patients. A Delphi study. Alarcón, MDL; Cabezón-Gutiérrez, L; Estévez, FV; Jiménez-López, AJ; Martín-Arroyo, JMT; Padrós, MC; Rebollo, MA; Sanz-Yagüe, A, 2019)	0.51
" The purpose of this study is to determine the efficacy of subanesthetic dosing of ketamine during TKA on postoperative pain and narcotic consumption."	( Intraoperative Ketamine in Total Knee Arthroplasty Does Not Decrease Pain and Narcotic Consumption: A Prospective Randomized Controlled Trial. Emper, WD; Freedman, KB; Good, RP; Levicoff, EA; Longenecker, AS; McComb, JJ; Rhee, JH; Shaner, JL; Tan, TL, 2019)	0.51
"15 mg/kg) in ≤6 hours after morphine dosing on postoperative day 1 and were evaluated for 24 hours."	( Analgesic Efficacy and Safety of Intravenous Meloxicam in Subjects With Moderate-to-Severe Pain After Open Abdominal Hysterectomy: A Phase 2 Randomized Clinical Trial. Du, W; Freyer, A; Mack, RJ; McCallum, SW; Rechberger, T, 2019)	0.81
" Once-daily administration of meloxicam IV produced analgesic effect within 6-8 minutes postdose that was maintained over a 24-hour dosing interval."	( Analgesic Efficacy and Safety of Intravenous Meloxicam in Subjects With Moderate-to-Severe Pain After Open Abdominal Hysterectomy: A Phase 2 Randomized Clinical Trial. Du, W; Freyer, A; Mack, RJ; McCallum, SW; Rechberger, T, 2019)	0.51
" This study measured differences in cognitive behavior performance on the object recognition test (ORT) and social recognition test (SRT) and serum levels of corticosterone (CORT) between C57BL/6J and BALB/cJ mice after 14-day chronic exposure to either cocaine (5 mg/kg) or morphine (3 mg/kg) at a dosage of 10 ml/kg/day."	( Differences in cocaine- and morphine-induced cognitive impairments and serum corticosterone between C57BL/6J and BALB/cJ mice. Chao, R; Chen, L; Gong, D; Liang, Y; Yang, S; Yu, P; Zhao, H, 2019)	0.99
" Multivariate binary regression analysis assessed these MME dosage categories."	( Total Inpatient Morphine Milligram Equivalents Can Predict Long-term Opioid Use After Transforaminal Lumbar Interbody Fusion. Buckland, AJ; Errico, TJ; Fischer, CR; Ge, DH; Hockley, A; Moawad, MA; Passias, PG; Protopsaltis, TS; Vasquez-Montes, D, 2019)	0.86
"48 mL/day of saline or MS dosing (12 mg/day at 25 mg/mL) as boluses: x1 (q24hour), x2 (q12hour), x4 (q6hour), or x8 (q3hour) given at the rate of 1000 μL/hour, or as a continuous infusion (25 mg/mL/20 μL/hour)."	( Characterization of Effect of Repeated Bolus or Continuous Intrathecal Infusion of Morphine on Spinal Mass Formation in the Dog. Arjomand, S; Billstrom, TM; Eddinger, KA; Hildebrand, KR; Page, LM; Steinauer, JJ; Yaksh, TL, 2019)	0.74
" A dose-response trend was observed for constipation but not for the other side effects."	( Side effects from opioids used for acute pain after emergency department discharge. Castonguay, V; Chauny, JM; Cournoyer, A; Daoust, R; Lessard, J; Morris, J; Paquet, J; Piette, É; Williamson, D, 2020)	0.56
" The current study examines the impact of non-contingent acute, repeated, and withdrawal-inducing morphine dosing regimens on glutamate transmission in D1- or D2-MSNs in the nucleus accumbens shell (NAcSh) and core (NAcC) sub-regions in hopes of identifying excitatory plasticity that may contribute to unique facets of opioid addiction-related behavior."	( Cell-type and region-specific nucleus accumbens AMPAR plasticity associated with morphine reward, reinstatement, and spontaneous withdrawal. Anderson, EM; Gomez, D; Hearing, MC; Ingebretson, AE; Madayag, AC; Thomas, MJ, 2019)	0.96
"The medical condition and baseline opioid requirements must all be carefully considered when dosing a fentanyl patch."	( Consensus Perioperative Management Best Practices for Patients on Transdermal Fentanyl Patches Undergoing Surgery. Cornett, EM; Ehrhardt, KP; Fox, CJ; Gennuso, SA; Kaye, AD; Menard, BL; Okereke, EC; Tirumala, SR, 2019)	0.51
" Results showed that all subjects who consumed low dosage of poppy seeds either in single meal or multiple meals experiment were found negative."	( Profiling of morphine and codeine in urine after the ingestion of curry containing poppy seed as an evidence for opiates defence in Malaysia. Gan, CY; Isahak, M; Mahad, NH; Mohd Akir, F; Mohd Fazil, NF; Muhamad Noh, H; Nasir, R; Rahmat, R; Samad, HA; Zainuddin, Z, 2019)	0.88
" Pupil constriction, confirming central nervous system μ-opioid receptor engagement, correlated with higher plasma TRV734 concentrations; the greatest reductions in pupil diameter occurring between 0 and 4 hours after dosing (-2."	( A First-in-Human Clinical Study With TRV734, an Orally Bioavailable G-Protein-Biased Ligand at the μ-Opioid Receptor. Fossler, MJ; James, IE; Ramos, KA; Ruff, D; Skobieranda, F; Soergel, DG, 2020)	0.56
" Furthermore, enduring exacerbation of nociceptive hypersensitivity is also observed when the same dosing regimen for either morphine, fentanyl, or oxycodone begins 1 month after nerve injury."	( Oxycodone, fentanyl, and morphine amplify established neuropathic pain in male rats. Ball, JB; Fabisiak, T; Grace, PM; Green-Fulgham, SM; Kwilasz, AJ; Maier, SF; Watkins, LR, 2019)	1.02
" This represents a potential 21% reduction in daily opioid dosage when compared with LA patients and 18."	( Postoperative Opioid Consumption After Total Hip Arthroplasty: A Comparison of Three Surgical Approaches. Quinn, M; Seah, S; Tirosh, O; Tran, P, 2019)	0.51
" Optimal standardized dosing and drug combination for preoperative multimodal analgesia remains to be elucidated."	( Preoperative multimodal analgesia decreases 24-hour postoperative narcotic consumption in elective spinal fusion patients. Haffner, M; Hwang, J; Klineberg, E; Migdal, C; Nathe, R; Roberto, R; Saiz, AM, 2019)	0.51
" Few data deal with the initial dosage of each drug."	( Optimizing Initial Intrathecal Drug Ratio for Refractory Cancer-Related Pain for Early Pain Relief. A Retrospective Monocentric Study. Bore, F; Carvajal, G; Delorme, T; Demelliez-Merceron, S; Dubois, PY; Dupoiron, D; Jubier-Hamon, S; Leblanc, D; Lebrec, N; Pechard, M; Robard, S; Seegers, V, 2019)	0.51
"We found that overall and spine-related health care costs, and the use and dosage of opioids increased significantly with chronic pain impact levels."	( Health Care Costs and Opioid Use Associated With High-impact Chronic Spinal Pain in the United States. Broten, N; Coulter, ID; Herman, PM; Lavelle, TA; Sorbero, ME, 2019)	0.51
"The benefits related to rescue dosing further inform the development of a standardized NAS treatment protocol."	( Treating infants with neonatal abstinence syndrome: an examination of three protocols. Hartgrove, MJ; King, TL; Meschke, LL; Saunders, C, 2019)	0.51
"5, 5, and 10 mg/kg, respectively); (2) increasing morphine dosage (2."	( Persistent Nociception Facilitates the Extinction of Morphine-Induced Conditioned Place Preference. Chen, L; Ding, W; Doheny, JT; Lim, G; Mao, J; Miao, J; Shen, S; Yang, J; Yang, L; You, Z, 2019)	1.02
" Morphine was used for pain management, provided by intravenous intermittent dosing (patient-controlled analgesia)."	( [Opioid-induced adrenal insufficiency: Case report and synthesis of the literature]. Arlet, JB; Flamarion, E; Khellaf, M; Michon, A; Passeron, A; Pouchot, J; Ranque, B; Saada, N, 2019)	1.42
"Oral morphine in a sufficient dosage given in combination with other medications was effective and well tolerated when used to control pain during upper-limb fracture reduction."	( Evaluation of an oral analgesia protocol for upper-limb fracture reduction in the paediatric emergency department: Prospective study of 101 patients. Chasle, V; de Giorgis, T; Desgranges, M; Farges, C; Guitteny, MA; Herve, T; Longuet, R; Metreau, Z; Ryckewaert, A; Violas, P, 2019)	1.03
" Opioid dosage and cancer pain score were recorded daily for 2 consecutive weeks before and 2 weeks after the ACT infusions."	( Adoptive immunotherapy with autologous T-cell infusions reduces opioid requirements in advanced cancer patients. Hobeika, A; Lyerly, HK; Morse, MA; Qiao, G; Ren, J; Wang, S; Wang, X; Yuan, Y; Zhou, X; Zhu, S, 2020)	0.56
" Inadequate pain control in neonates can cause long-term adverse consequences; however, providing appropriate individualized morphine dosing is particularly challenging due to the interplay of rapid natural physiological changes and multiple life-sustaining procedures in patients who cannot describe their symptoms."	( Electronic Health Record-Embedded Decision Support Platform for Morphine Precision Dosing in Neonates. Butler, D; Cortezzo, DE; Dietrich, T; Dufendach, KR; Duggan, TJ; Euteneuer, JC; Keefer, R; Kiger, S; Kirkendall, E; Menke, F; Mizuno, T; Punt, NC; Setchell, KDR; Spencer, P; Vinks, AA; Zhao, J, 2020)	1
" Primary care clinicians and surgeons should monitor the duration and dosage of perioperative opioid use."	( Opioid use prior to elective surgery is strongly associated with persistent use following surgery: an analysis of 14 354 Medicare patients. Barrington, MJ; Catchpool, M; Choong, PFM; Clarke, P; Dowsey, MM; Knight, J; Young, JT, 2019)	0.51
" The spinal cord was removed for the lipoperoxidation dosing of the membranes."	( Recombinant peptide derived from the venom the Phoneutria nigriventer spider relieves nociception by nerve deafferentation. Angelo, SG; Antunes, FTT; Dallegrave, E; de Souza, AH; Ferraz, AG; Gomez, MV; Marroni, NP; Picada, JN; Schemitt, E, 2020)	0.56
" Blockade of peripheral nociceptive inputs prevented chronic morphine-induced increases in spinal SP, NR1, and TRPV1 and a rightward shift of the morphine dose-response curve in the CCI model."	( Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model. Jiang, W; Kim, DK; Ma, X; Wang, A; Xing, Y; Xu, T; Zhong, W, 2020)	1.01
" Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols."	( Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy. Coetzee, JF; Hartnack, AK; Kleinhenz, MD; Lakritz, J; Niehaus, AJ, 2020)	0.8
" Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals."	( Analgesic efficacy of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy. Coetzee, JF; Hartnack, AK; Kleinhenz, MD; Lakritz, J; Niehaus, AJ, 2020)	0.8
" In this work, we present a sequential decision making framework for opioid dosing based on deep reinforcement learning."	( Deep Reinforcement Learning for Optimal Critical Care Pain Management with Morphine using Dueling Double-Deep Q Networks. Eschenfeldt, P; Hur, C; Ingram, M; Lopez-Martinez, D; Ostvar, S; Picard, R, 2019)	0.74
" As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience."	( Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration. Birras, J; Diez Bernal, S; Mirra, A; Spadavecchia, C, 2020)	2.23
" Repetitive dosing to induce anti-nociceptive tolerance increases blood-borne MPs by 8-fold, and by 10-fold in deep cervical lymph nodes draining brain glymphatics."	( Blood-borne and brain-derived microparticles in morphine-induced anti-nociceptive tolerance. Bhopale, VM; Greenblatt, A; Ruhela, D; Thom, SR; Weintraub, E; Yang, M; Yu, K, 2020)	0.81
" When a stable dose of opioids is established, people still experience episodic breakthrough pain for which dosing of an immediate release opioid is usually a proportion of the total daily dose."	( A randomized, double-blind, crossover, dose ranging study to determine the optimal dose of oral opioid to treat breakthrough pain for patients with advanced cancer already established on regular opioids. Clark, K; Currow, DC; Fazekas, B; Greene, A; Louw, S; Sanderson, CR, 2020)	0.56
" For infants receiving morphine, the cumulative morphine dosage was calculated."	( Morphine affects brain activity and volumes in preterms: An observational multi-center study. Benders, MJNL; Claessens, NHP; de Vries, LS; Fellman, V; Groenendaal, F; Gui, L; Hellström-Westas, L; Huppi, P; Sävman, K; Schuurmans, J; Tataranno, ML; Toet, M, 2020)	2.31
" This study looks to establish a safe and efficacious fixed bupivacaine dosing algorithm in intrathecal pumps for cancer patients."	( Evaluation of Fixed Intrathecal Bupivacaine Infusion Doses in the Oncologic Population. Baig, E; Chen, GH; Clement, K; Gulati, A; Laufer, I; Magram, YC; Spiegel, MA, 2020)	0.56
"A bupivacaine dosing algorithm was developed using data from 120 previous patients who underwent IDDS placement at Memorial Sloan Kettering Cancer Center."	( Evaluation of Fixed Intrathecal Bupivacaine Infusion Doses in the Oncologic Population. Baig, E; Chen, GH; Clement, K; Gulati, A; Laufer, I; Magram, YC; Spiegel, MA, 2020)	0.56
" Although the current literature provides dosing guidelines for the average infant, it fails to control for the large unexplained variability in morphine clearance and response in individual patients."	( Model-Informed Bayesian Estimation Improves the Prediction of Morphine Exposure in Neonates and Infants. Euteneuer, JC; Fukuda, T; Mizuno, T; Muglia, LJ; Setchell, KDR; Vinks, AA; Zhao, J, 2020)	1
" A further study is warranted to elucidate the predictive covariates and precision dosing strategies that use morphine concentration and pain scores as feedbacks."	( Model-Informed Bayesian Estimation Improves the Prediction of Morphine Exposure in Neonates and Infants. Euteneuer, JC; Fukuda, T; Mizuno, T; Muglia, LJ; Setchell, KDR; Vinks, AA; Zhao, J, 2020)	1.01
"To investigate the correlations of analgesic dosage of morphine with solute carrier family 6 member 4 (SLC6A4) gene polymorphisms in patients with lung cancer."	( Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer. Guo, H; Han, X; Song, HJ; Xin, XF; Zhu, XL, 2020)	1.08
" Visual Analogue Scale (VAS) was applied to grade the pain, the patients in cancer pain group were treated with morphine, and the dosage of morphine within 24 h was recorded."	( Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer. Guo, H; Han, X; Song, HJ; Xin, XF; Zhu, XL, 2020)	1.04
" The analgesic dosage of morphine for the lung cancer patients was prominently correlated with the genotypes of SLC6A4 gene rs1042173 in cancer pain group."	( Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer. Guo, H; Han, X; Song, HJ; Xin, XF; Zhu, XL, 2020)	1.14
"The morphine dosage for analgesia has significant correlations with SLC6A4 gene polymorphisms in patients with lung cancer."	( Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer. Guo, H; Han, X; Song, HJ; Xin, XF; Zhu, XL, 2020)	1.39
" However, their use is restricted by such factors as tolerance and opioid-induced hyperalgesia (OIH), so it is critical to find ways to reduce the dosage of opioids to avoid the side effects."	( A20 enhances mu-opioid receptor function by inhibiting beta-arrestin2 recruitment. Li, Y; Shao, S; Su, R; Sun, Y; Tan, B; Tian, X; Zhang, Y, 2020)	0.56
"The present series of studies examine the impact of systemically administered therapeutics on peripheral nerve injury (males; unilateral sciatic chronic constriction injury [CCI])-induced suppression of voluntary wheel running, across weeks after dosing cessation."	( Suppression of active phase voluntary wheel running in male rats by unilateral chronic constriction injury: Enduring therapeutic effects of a brief treatment of morphine combined with TLR4 or P2X7 antagonists. Ball, JB; Grace, PM; Green-Fulgham, SM; Maier, SF; Rice, KC; Watkins, LR, 2022)	0.92
" In this exploratory analysis, we report dosing interruption (DI) and average cumulative duration of DI (CDDI) for both oliceridine and morphine."	( Evaluating the Incidence of Opioid-Induced Respiratory Depression Associated with Oliceridine and Morphine as Measured by the Frequency and Average Cumulative Duration of Dosing Interruption in Patients Treated for Acute Postoperative Pain. Ayad, S; Burt, DA; Demitrack, MA; Fossler, MJ; Khanna, AK; Michalsky, C; Wase, L, 2020)	0.98
" Secondary endpoints include pain intensity as assessed with the numerical rating scale (NRS) for pain, time to return of intestinal function (defined as the time to first flatus and the time to the first postoperative intake of solid food), time to first mobilization, the incidence of postoperative nausea and vomiting during the first 24 h, length of stay on the post anesthesia care unit (PACU) and in the hospital, the extent of sensory block at two time points (admission to and discharge from the PACU), the doses of morphine IV as requested by the patient from the PCA pump, the total dosage of morphine administered IV, the need for and dose of rescue analgesics (ketamine, clonidine), free plasma ropivacaine levels after induction and at discharge from the PACU, and the incidence of adverse events during treatment (in particular, signs of local anesthetic systemic toxicity (LAST))."	( Transmuscular quadratus lumborum (TQL) block for laparoscopic colorectal surgery: study protocol for a double-blind, prospective randomized placebo-controlled trial. Coppens, S; D'Hoore, A; Dewinter, G; Fieuws, S; Neyrinck, A; Rex, S, 2020)	0.72
" On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922."	( Switching opioid-dependent patients in substitution treatment from racemic methadone, levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care. Baschirotto, C; Kuhn, S; Lehmann, K; Reimer, J; Verthein, U, 2020)	0.76
" Inhibition of HCN2 also showed a partial preventive effect on morphine-induced tolerance, hypothermia tolerance and also the right-shift of the dose-response curve."	( Chronic morphine induces cyclic adenosine monophosphate formation and hyperpolarization-activated cyclic nucleotide-gated channel expression in the spinal cord of mice. Chen, D; Chen, J; Luo, L; Ma, X; Shi, H; Wang, W; Xu, T; Yu, K; Yuan, L, 2020)	1.23
" We believe lower morphine dosage using PCA protocol according to the rapidly changing pain levels of the patients will provide effective analgesia."	( Patient-controlled analgesia and morphine consumption in sickle cell anemia painful crises: A new protocol. Bakır, M; Rumeli Atıcı, Ş; Tiftik, EN; Ünal, S; Yıldırım, HU, 2020)	1.17
" Secondary outcomes included postoperative pain score, time to first and total dosage of rescue morphine in postoperative 48 hours, early and late postoperative period (from postoperative day 0-3 months follow-up) performance-based test (Timed-Up and Go test, and quadriceps strength)."	( The efficacy and safety of the infiltration of the interspace between the popliteal artery and the capsule of the knee block in total knee arthroplasty: A prospective randomized trial protocol. Cong, Z; Ma, F; Zhang, L, 2020)	0.78
" This paper provides a review of the pharmacokinetics (PK) of the IV tramadol dosing regimen being developed in the United States, its abuse potential as documented in the literature, and its safety record in clinical practice, and discusses how IV tramadol may become a useful option for patients in the United States with acute pain."	( IV tramadol: A novel option for US patients with acute pain-A review of its pharmacokinetics, abuse potential and clinical safety record. Harnett, M; Lu, L; Reines, SA, )	0.13
"To compare the analgesic efficacy of two techniques of morphine titration (intermittent intravenous bolus vs infusion) by calculating rescue dosage in a day at 1 week after analgesic titration."	( Comparison of two techniques (intermittent intravenous bolus morphine vs. morphine infusion) for analgesic titration in patients who had advanced cancer with severe pain: a prospective randomised study. Bharti, SJ; Bhatnagar, S; Garg, R; Gupta, N; Kumar, V; Mishra, S; Sirohiya, P; Velpandian, T, 2023)	1.4
"A number of recent studies have investigated the optimal dosage and timing of dexamethasone in total hip arthroplasty (THA) but have inconsistent findings."	( What is the optimal regimen for intravenous dexamethasone administration in primary total hip arthroplasty?: A protocol of randomized controlled trial. Liang, D; Liu, W; Wang, Y; Xue, C, 2020)	0.56
"Low concentrations of morphine are required for safe dosing for intrathecal injections."	( Measurement of drug concentration and bacterial contamination after diluting morphine for intrathecal administration: an experimental study. de Bruijn, B; Koning, MV; Koopman, SA; Liefers, WJ; Ruijgrok, EJ; Teunissen, AJW, 2020)	1.1
" A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1."	( Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity. Aw, N; Baccarelli, AA; Baker, BH; Bellenger, JP; Boivin, A; Gillet, V; Laue, HE; Lepage, JF; Lugo-Candelas, C; Posner, J; Rahman, T; Takser, L; Whittingstall, K; Wu, H, 2020)	0.56
" Morphine consumption during operation, postoperatively in the first 24 hours and total dosage until discharge and its side effects were also observed."	( Does Ultrasound-Guided Transversus Abdominis Plane Block Reduce Donor Site Pain After Harvesting Anterior Iliac Crest Bone Grafts. Sowapark, J; Sumphaongern, T, 2021)	1.53
" Currently, the morphine dosing strategies are empiric, not optimal and associated with longer hospital stay."	( Model-Based Approach to Improve Clinical Outcomes in Neonates With Opioid Withdrawal Syndrome Using Real-World Data. Aduroja, O; Biggs, JM; El-Metwally, D; Gopalakrishnan, M; Wijekoon, N, 2021)	0.97
"Gene polymorphism is an important factor affecting the efficacy and dosage of opioids."	( Resistin Gene Polymorphism Is an Influencing Factor of Postoperative Pain for Chinese Patients. Chen, Z; Fan, Q; Ge, W; Li, D; Ma, Z; Shu, Q; Xie, H, 2020)	0.56
"Using county-level quarterly data from 2012 to 2017, we estimated the absolute change associated with the implementation of these two PDMP features in seven prescribing indicators in California versus a control group comprising counties in Florida and Washington: opioid prescription rate per 1000 residents; patients' mean daily opioid dosage in milligrams of morphine equivalents[MME]; prescribers' mean daily MME prescribed; prescribers' mean number of opioid prescriptions per day; percentage of patients getting >90 MME/day; percentage of days with overlapping prescriptions for opioids and benzodiazepines; multiple opioid provider episodes per 100,000 residents."	( Changes in opioid prescribing after implementation of mandatory registration and proactive reports within California's prescription drug monitoring program. Castillo-Carniglia, A; Cerdá, M; Delcher, C; González-Santa Cruz, A; Henry, SG; Shev, AB; Wintemute, GJ, 2021)	0.79
" Herein we evaluate the effects of acute and repeated dosing of SR-17018, oxycodone and morphine in additional models of pain-related behaviors."	( Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain. Acevedo-Canabal, A; Bannister, TD; Bohn, LM; Cameron, MD; Grim, TW; Kennedy, NM; Pantouli, F; Schmid, CL, 2021)	1.2
" This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS."	( Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches. Akinbi, H; Butler, D; Emoto, C; Fukuda, T; McPhail, BT; Vinks, AA, 2021)	0.62
" In the second experiment, rats received six repeated morphine injections with different interdose intervals (two per day, one per day, every other day, every fourth day), and morphine effects were re-determined 1 day after the last dose to determine dosing frequencies sufficient to produce enhanced opioid reward."	( Temporal parameters of enhanced opioid reward after initial opioid exposure in rats. Moerke, MJ; Negus, SS, 2021)	0.87
" The second experiment indicated that all dosing frequencies tested were sufficient to produce enhanced reward."	( Temporal parameters of enhanced opioid reward after initial opioid exposure in rats. Moerke, MJ; Negus, SS, 2021)	0.62
"Taken together, these results suggest that enhancement of opioid reward after initial opioid exposure is relatively transient but can be produced by a range of different dosing frequencies."	( Temporal parameters of enhanced opioid reward after initial opioid exposure in rats. Moerke, MJ; Negus, SS, 2021)	0.62
" Also, it may be associated with a lower incidence of adverse events at dosing regimens associated with comparable analgesia."	( Oliceridine for the Management of Acute Postoperative Pain. Hu, Q; Liu, Y; Yang, J, 2021)	0.62
"Compared with a conservative dosing approach, this individualized protocol may improve analgesia without a significant increase in respiratory adverse events."	( Effects of an individualized analgesia protocol on the need for medical interventions after adenotonsillectomy in children: a randomized controlled trial. Guo, J; Liu, K; Wan, Y; Wang, X; Zhuang, P, 2021)	0.62
" We also examined the effect of ECS on the dose-response curve of %MPE to morphine-antinociception."	( Enhancement of morphine-induced antinociception after electroconvulsive shock in mice. Doi, N; Ikeda, K; Iwata, K; Takamatsu, Y, )	0.72
"Mother-baby nurses can have an impact on the practice of anesthesia providers by advocating for evidence-based dosing of intrathecal morphine to reduce the incidence of pruritis while maintaining effective analgesia for women after cesarean birth."	( Prevention of Pruritis following Spinal Morphine for Scheduled Cesarean Birth. Curtis, B; Dan, D; Dunston, S; Hefley, J; Moore, C; Payne, C, )	0.6
"To assess the efficacy and safety of intrathecal morphine (ITM) for postoperative analgesia in primary total joint arthroplasty (TJA) under spinal anesthesia and to explore the dose-response relationship for analgesic efficacy or risk of side effects."	( The Role of Intrathecal Morphine for Postoperative Analgesia in Primary Total Joint Arthroplasty under Spinal Anesthesia: A Systematic Review and Meta-Analysis. Wang, GL; Wang, LM; Yao, RZ; Zhang, Z, 2021)	1.18
" Meta-regression was used to explore the dose-response relationship."	( The Role of Intrathecal Morphine for Postoperative Analgesia in Primary Total Joint Arthroplasty under Spinal Anesthesia: A Systematic Review and Meta-Analysis. Wang, GL; Wang, LM; Yao, RZ; Zhang, Z, 2021)	0.93
" Furthermore, meta-regression showed a linear dose-response relationship for the postoperative 24-h morphine consumption but no linear dose-response relationship for the risk of side effects."	( The Role of Intrathecal Morphine for Postoperative Analgesia in Primary Total Joint Arthroplasty under Spinal Anesthesia: A Systematic Review and Meta-Analysis. Wang, GL; Wang, LM; Yao, RZ; Zhang, Z, 2021)	1.14
" Although we found a linear dose-response relationship for the postoperative 24-h morphine consumption, the optimal dose of ITM remains to be further explored in high-quality RCTs with a large sample size."	( The Role of Intrathecal Morphine for Postoperative Analgesia in Primary Total Joint Arthroplasty under Spinal Anesthesia: A Systematic Review and Meta-Analysis. Wang, GL; Wang, LM; Yao, RZ; Zhang, Z, 2021)	1.15
" We included any duration of drug treatment and any dosage given continuously or as bolus; we excluded studies that gave opioids to ventilated infants for procedures."	( Opioids for newborn infants receiving mechanical ventilation. Bellù, R; Bruschettini, M; de Waal, KA; Nava, C; Romantsik, O; Zanini, R, 2021)	0.62
" Opioid prescribing was characterized in terms of morphine equivalent daily dosing (MEDD), total morphine equivalent dosing (TMED), and total number of opioid prescriptions."	( Opioid Prescribing Patterns and Patient Satisfaction with Care. Bockelman, CK; Elsenbeck, CMJ; Foster, MJN; Lanham, MNS; McCriskin, LBJ; Robinson, MPSH; Rumley, MRJCL, 2021)	0.87
" Dexmedetomidine, as an alternative to morphine, has several appealing characteristics, including neuroprotective effects in animal models; robust pharmacokinetic studies in neonates with NE treated with TH are required to ensure a safe and effective standard dosing approach."	( Management of comfort and sedation in neonates with neonatal encephalopathy treated with therapeutic hypothermia. Frymoyer, A; Groenendaal, F; McPherson, C; Miller, SP; Ortinau, CM, 2021)	0.89
" The aim of this retrospective, longitudinal study from 2012 to 2016 was to assess how intraoperative opioid dosing varies by patient and clinical care factors and across multiple institutions over time."	( Practice Patterns and Variability in Intraoperative Opioid Utilization: A Report From the Multicenter Perioperative Outcomes Group. Brummett, CM; Domino, KB; Durieux, ME; Kheterpal, S; Kuck, K; Naik, BI; Pace, NL; Posner, KL; Saager, L; Sinha, A; Stuart, A; Vaughn, MT, 2022)	0.72
" While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked."	( Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats. Dietis, N; Gueven, N; Paul, AK, 2021)	1.13
" Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen."	( Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. Aizenberg, DA; Applegate, RL; Funamura, JL; Hall, B; Kriss, RS; Lammers, CR; Nittur, V; Schwinghammer, AJ; Senders, CW, 2021)	0.62
"Many people with chronic pain escalate their opioid dosage to counteract tolerance effects."	( Escalating morphine dosage fails to elicit conditioned analgesia in a preclinical chronic neuropathic pain model. Boorman, DC; Keay, KA, 2021)	1.01
"The objective of this work was to develop a risk prediction model for opioid overdose and opioid use disorder for patients at first opioid prescription and compare the predictive accuracy of morphine equivalent total dosage with the predictive accuracy of daily dosage ."	( Morphine Equivalent Total Dosage as Predictor of Adverse Outcomes in Opioid Prescribing. Bonifonte, A; Deppen, K; Merchant, R, 2021)	2.25
" Morphine equivalent total dosage of opioid prescriptions was identified as a stronger predictor of adverse outcomes (C = 0."	( Morphine Equivalent Total Dosage as Predictor of Adverse Outcomes in Opioid Prescribing. Bonifonte, A; Deppen, K; Merchant, R, 2021)	2.97
"These findings demonstrate the value of including morphine equivalent total dosage as a predictor of adverse opioid outcomes and suggest that total dosage may be more strongly correlated with increased risk than daily dosage."	( Morphine Equivalent Total Dosage as Predictor of Adverse Outcomes in Opioid Prescribing. Bonifonte, A; Deppen, K; Merchant, R, 2021)	2.32
" We report on our experience using a 100:1 oral-to-intrathecal morphine conversion ratio for initial dosing and factors predictive of early dose escalation."	( Initial Intrathecal Dose Titration and Predictors of Early Dose Escalation in Patients With Cancer Using a 100:1 Oral to Intrathecal Morphine Conversion Ratio. Brogan, SE; Odell, DW; Presson, AP; Sindt, JE; Tariq, R; Zhang, C, 2021)	1.06
" The median oral-to-intrathecal morphine conversion ratio for initial IDD dosing was 105."	( Initial Intrathecal Dose Titration and Predictors of Early Dose Escalation in Patients With Cancer Using a 100:1 Oral to Intrathecal Morphine Conversion Ratio. Brogan, SE; Odell, DW; Presson, AP; Sindt, JE; Tariq, R; Zhang, C, 2021)	1.11
" These findings support a dosing regimen previously suggested by Krekels et al, which would put >95% of patients within this morphine target concentration range at steady state."	( Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children. Ceelie, I; de Kluis, T; de Wildt, SN; Goulooze, SC; Knibbe, CAJ; Krekels, EHJ; Tibboel, D; van Dijk, M, 2022)	1.2
" Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated."	( Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD). de Hosson, SM; Heller-Baan, R; Kerstjens, HAM; Lam-Wong, WY; Mooren, KJM; Peters, L; Pool, K; van Beurden-Moeskops, WJC; van den Berg, JK; van Dijk, M, 2021)	0.83
" Post hoc analyses were employed to compare PONV among patients based on MEQ dosage and antiemetic prophylaxis regimes."	( A Comprehensive Single-Center Analysis of Postoperative Nausea and Vomiting Following Orthognathic Surgery. Allam, O; Chandler, L; Dinis, J; Lopez, J; Maniskas, S; Park, KE; Peck, CJ; Pourtaheri, N; Smetona, J; Steinbacher, DM; Wilson, A; Yang, J, )	0.13
" SCH221510 (3 mg/kg, sc) attenuated but SB612111 (10 mg/kg, sc) enhanced morphine-induced antinociception, with rightward and leftward shift of morphine dose-response curves, respectively."	( Involvement of the nociceptin opioid peptide receptor in morphine-induced antinociception, tolerance and physical dependence in female mice. Chen, JM; Hao, XQ; Li, J; Wang, ZY; Wu, N, 2021)	1.1
" It is metabolised by the liver and appropriate administration and dosage is in question in in patients undergoing hepatectomy."	( The efficacy and safety of acetaminophen use following liver resection: a systematic review. Koea, J; Murphy, V; Srinivasa, S, 2022)	0.72
"Use of acetaminophen for adult patients undergoing liver resection surgery as post-operative analgesia at a standard dosage is safe for baseline analgesia."	( The efficacy and safety of acetaminophen use following liver resection: a systematic review. Koea, J; Murphy, V; Srinivasa, S, 2022)	0.72
"A multidisciplinary committee created a sedation guideline that included standardized dexmedetomidine dosing escalation and weaning."	( Reducing Benzodiazepine Exposure by Instituting a Guideline for Dexmedetomidine Usage in the NICU. Hansen, A; Labrecque, M; Leeman, K; Moline, M; Morton, SU, 2021)	0.62
"This study was conducted to investigate the influence of μ-opioid receptor gene (OPRM1) A118G polymorphism on dosage of morphine in advanced liver cancer patients."	( The Influence of OPRM1 A118G Polymorphism on the Dosage of Morphine in Patients with Advanced Liver Cancer. Cheng, H; Chu, X; Yi, S, 2021)	1.07
" Application of maraviroc with morphine can reduce effective dosage of morphine 2,3 fold."	( [Potential application of maraviroc in the therapy of neuropathic pain]. Olakowska, E; Sojka, P; Właszczuk, A, 2021)	0.91
" The former group had opioid prescriptions issued at regular intervals for stable, scheduled doses of opioids; the latter group had opioid prescriptions issued irregularly or for changed daily dosing regimen, for as-needed use, or had changes in the dosing regimen or inactive prescriptions mislabeled as active."	( Using electronic health record's data to assess daily dose of opioids prescribed for outpatients with chronic non-cancer pain. Sehgal, N; Tuan, WJ; Zgierska, AE, 2021)	0.62
" A secondary measure of opioid prescriptions (morphine milligram Eq [MME] dosage per patient) was tracked over time."	( Opioid Reduction Through Postoperative Pain Management in Pediatric Orthopedic Surgery. Bigham, MT; Engler, L; Farid, I; Fonte, E; Jones, K, 2021)	0.88
" Mice were treated with a 7-day escalating dosing scheme of morphine (20-100 mg/kg; IP) or saline and underwent a spontaneous withdrawal."	( Weight-gain propensity and morphine withdrawal alters locomotor behavior and regional norepinephrine-related gene expression in male and female mice. Bello, NT; Kshatriya, D; Li, X, 2022)	1.26
" Time-concentration profiles of diamorphine and its metabolites reflected disposition changes with age and were used to describe intravenous and intranasal dosing regimens."	( Pharmacokinetic modeling and simulation to understand diamorphine dose-response in neonates, children, and adolescents. Anderson, BJ; Gastine, S; Morse, JD; Standing, JF; Wong, ICK, 2022)	1.24
"Strict adherence to pharmacological dosage regimens is a prerequisite to the success of most treatments, particularly for patients in drug abuse programs."	( Urinalysis based assessment of compliance and drug use patterns in patients prescribed tramadol: A cross-sectional study from a tertiary care centre. Ghosh, S; Jain, R; Saifi, N; Sarkar, S, 2022)	0.72
" The dosage over time did not change in patients older than 64; in younger patients, there was a non-significant increasing trend."	( [Cannabinoids reduce opioid use in older patients with pain : Retrospective three-year analysis of data from a general practice]. Böhm, R; Gastmeier, A; Gastmeier, K; Herdegen, T; Rottmann, F, 2023)	0.91
" There were no significant differences in NOWS hospital outcomes between groups in adjusted models: transition to scheduled dosing (methadone 31."	( Neonatal Opioid Withdrawal Syndrome: A Comparison of As-Needed Pharmacotherapy. Gupta, M; MacMillan, KDL; Melvin, P; Morrison, TM; Murzycki, J; O'Shea, TF; Rothstein, R; Schiff, DM; Singh, R; Van Vleet, MW; Wachman, EM, 2022)	0.72
" The combination of additives and dosage are various and controversial."	( Efficacy of Periarticular Multimodal Analgesic Injection Containing High-Dose Ketorolac versus Triamcinolone in Early Postoperative Total Knee Arthroplasty: A Randomized Controlled Trial. Apinyankul, R; Goodman, SB; Lilakhunakon, K; Vechvitvarakul, M; Witayakom, W, 2022)	0.72
" Intensive care unit patients are especially at risk and pharmacokinetic modeling of drug concentrations is an approach to develop precision dosing strategies."	( Simultaneous detection of a panel of nine sedatives and metabolites in plasma from critically ill pediatric patients via UPLC-MS/MS. Bell, MJ; Birabaharan, J; Empey, PE; Nolin, TD; Traube, C; West, RE, 2022)	0.72
"Medication errors include the indirect dosing of drugs."	( Accuracy of Spinal Anesthesia Drug Concentrations in Mixtures Prepared by Anesthetists. Heesen, M; Schwappach, D; Steuer, C; Wiedemeier, P, 2022)	0.72
" In the long term, we observed an improvement on delay discounting correlated with the duration and dosage of SROM."	( Does slow release oral morphine have impact on craving and impulsivity in heroin dependent individuals? Calzada, G; Colombo, L; Giustiniani, J; Penzenstadler, L; Rothen, S; Thorens, G; Zullino, D, 2023)	1.22
" Greater intrathecal diamorphine dosing was positively associated with higher number of cases per month (rho=0."	( Intrathecal diamorphine for perioperative analgesia during colorectal surgery: a cross-sectional survey of current UK practice. Alderman, J; Gao-Smith, F; Morgese, C; Patel, J; Sharma, A, 2022)	1.38
" Therefore, high-quality randomised dose-response trials are needed to investigate the relationship between doses of intrathecal diamorphine and patient outcomes."	( Intrathecal diamorphine for perioperative analgesia during colorectal surgery: a cross-sectional survey of current UK practice. Alderman, J; Gao-Smith, F; Morgese, C; Patel, J; Sharma, A, 2022)	1.28
"Horses were treated with a single intravenous dosage of saline, morphine (0."	( Characterization of the pharmacokinetics, behavioral effects and effects on thermal nociception of morphine 6-glucuronide and morphine 3-glucuronide in horses. Fang, Y; Kanarr, K; Kass, PH; Knych, HK; McKemie, DS, 2022)	1.18
" West Palm Beach VA Healthcare System (WPBVAHCS) has been an outlier for the percentage of Veterans with chronic non-cancer pain receiving ≥90 mg Morphine Equivalent Daily Dosing (MEDD) in Veterans Integrated Service Networks (VISN) 8 since the 2016 fiscal year."	( Impact of Clinical Pharmacist Practitioner-Driven High Opioid Dose Reevaluation in Veterans with Chronic Non-Cancer Pain. Brooks, A; DiScala, SL; Faley, B; Vartan, CM, 2022)	0.92
" Three days of cumulative dosing were administered to establish morphine tolerance in rats."	( Metformin prevents morphine-induced apoptosis in rats with diabetic neuropathy: a possible mechanism for attenuating morphine tolerance. Avci, O; Gursoy, S; Inan, ZDS; Ozdemir, E; Taskiran, AS, 2022)	1.29
"Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain."	( Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial. Chen, H; Huang, C; Li, X; Lin, R; Lin, S; Liu, J; Lu, M; Luo, Y; Lv, X; Su, L; Wu, M; Zhang, Z; Zhao, S; Zhou, M; Zhu, J; Zou, H, 2022)	0.88
" Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department."	( The Effectiveness of Ketamine Compared to Opioid Analgesics for management of acute pain in Children in The Emergency Department: systematic Review. Alanazi, E, 2022)	0.72
" The aim of this project is to conduct a budget impact analysis to estimate the costs or savings associated with the changes in ziconotide dosage in addition to its use in combination with morphine for the management of cancer pain."	( Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis. Black, S; Copley, S; Duarte, R; Dupoiron, D; Eldabe, R; Eldabe, S; Kansal, A; Lambe, T, 2023)	1.1
"3 mg/kg) produced the same degree of rightward shift in the dose-response curves for heroin- and THC-induced antinociception, respectively."	( Functional consequences of short-term exposure to opioids versus cannabinoids in nonhuman primates. Ding, H; Kiguchi, N; Kishioka, S; Ko, MC; Mabry, KM, 2023)	0.91
" The daily average preoperative opioid dosage 90 days before fusion was determined as morphine equivalent dose and further categorized into high dose (morphine equivalent dose >100 mg/day) and low dose (1-100 mg/day)."	( Does Preoperative Opiate Choice Increase Risk of Postoperative Infection and Subsequent Surgery? Anandan, M; Corso, K; DeSimone, C; Franco, D; Gonzalez, GA; Harrop, J; Heller, JE; Hines, K; Jallo, J; Mahtabfar, A; Miao, J; O'Leary, M; Polanco, D; Porto, G; Qasba, R; Rajappan, SK; Sharan, A; Smit, R; Thalheimer, S; Wainwright, J, 2023)	1.13
" Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed."	( Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. Agar, MR; Chang, S; Clark, KJ; Currow, DC; Eckert, DJ; Ekström, M; Fazekas, B; Ferreira, D; Johnson, MJ; Louw, S, 2022)	1.25
" Dosing is often adjusted for adequate pain relief."	( Pharmacological data science perspective on fatal incidents of morphine treatment. Dudziak, R; Kringel, D; Lötsch, J; Noufal, Y; Toennes, SW, 2023)	1.15
" By exploring the dose-response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects."	( Minimal important difference in opioid consumption based on adverse event reduction-A study protocol. Gasbjerg, KS; Geisler, A; Hägi-Pedersen, D; Jakobsen, JC; Karlsen, APH; Laigaard, J; Lunn, TH; Mathiesen, O; Pedersen, C; Thybo, KH, 2023)	0.91
" Subjects were randomized to initial dosing to a T4 dermatome surgical anesthetic level with either 3% CP or 2% lidocaine with 1:200,000 epinephrine and sodium bicarbonate (LEB)."	( Postcesarean Analgesia With Epidural Morphine After Epidural 2-Chloroprocaine: A Randomized Noninferiority Trial. Lee, LO; Lu, M; Ramirez-Chapman, AL; Suresh, MS; White, DL; Zhang, X, 2023)	1.18
"While designed as an exploratory study, initial epidural dosing with 3% CP and beginning subsequent redosing with LEB within 30 minutes of the initial CP bolus provided noninferior postcesarean analgesia with epidural morphine compared to initial epidural dosing and redosing with LEB."	( Postcesarean Analgesia With Epidural Morphine After Epidural 2-Chloroprocaine: A Randomized Noninferiority Trial. Lee, LO; Lu, M; Ramirez-Chapman, AL; Suresh, MS; White, DL; Zhang, X, 2023)	1.37
"The new "cocktail" LIA with Diprospan can effectively reduce the early postoperative pain of THA, reduce the dosage of opioids, shorten the length of hospital stay, and is conducive to the early functional rehabilitation of patients."	( [Analgesic effect of a new "cocktail" of local infiltration analgesia after total hip arthroplasty-A prospective randomized controlled study]. Luo, Z; Wang, H; Xiao, Q; Yang, Q; Zhou, Z, 2022)	0.72
" The average concentration of cocaine detected in cardiac cases (900 ng/mL) was considerably lower than that detected in cases where acute (19,100 ng/mL) or chronic/binge (6,200 ng/mL) dosing was evident."	( From Bumps to Binges: Overview of Deaths Associated with Cocaine in England, Wales and Northern Ireland (2000-2019). Copeland, C; Rock, K; Rooney, B; Sobiecka, P, 2023)	0.91
" "High-risk" prescriptions were characterized by: days supplied >7, daily dosage ≥50 oral morphine equivalents (OMEs), opioid-benzodiazepine overlap, and extended-release/long-acting opioid."	( Safety and Distribution of Opioid Prescribing by U.S. Surgeons. Bicket, MC; Brummett, CM; Chua, KP; Gunaseelan, V; Waljee, JF, 2023)	1.13
" Male and female national institute of health (NIH) Swiss mice were made dependent upon morphine using an escalating dosing schedule."	( Modeling spontaneous opioid withdrawal in male and female outbred mice using traditional endpoints and hyperalgesia. Blokker, A; Brewer, AL; Burkland, JA; Eggerman, L; Johnsen, M; Lewis, CC; Quock, RM, 2023)	1.13
" ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively."	( The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths. Ajao, A; Chai, GP; Ding, Y; Gill, R; Karami, S; Major, JM; McAninch, J; Meyer, T; Secora, A; Wong, J; Zhang, D; Zhao, Y, 2023)	1.11
" Oral and injectable naltrexone administration is the most widely used, presenting some inconveniences: poor patient adherence to the oral daily dosing schedule, cases of hepatitis and clinically significant liver dysfunction."	( Promising biomedical subcutaneous delivery system in opioid disaccustom process: In vitro/in vivo evaluation of naloxone microparticles on antagonist effect of morphine. Benéitez García, MC; Colmena Crespo, I; Díez-Orejas, RM; Gil-Alegre, ME; Girón Moreno, R; Goicoechea García, C; Martín Fontelles, MI; Sánchez-Robles, EM, 2023)	1.11
"Based on reimbursed bills, we calculated the dosage (morphine equivalent dose, MED) and the episode length (acute: <90 days; subacute: ≥90 to <120 days or <10 claims; chronic: ≥90 days and ≥10 claims or ≥120 days)."	( Opioid prescriptions after knee replacement: a retrospective study of pathways and prognostic factors in the Swiss healthcare setting. Bähler, C; Blozik, E; Boes, S; Huber, CA; Näpflin, M; Wirth, K, 2023)	1.16
"Individual dose-response curves (DRCs) of PEA, MOR and GBP were evaluated in female mice in which intraplantar nociception was induced with 2% formalin."	( N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice. Aguilera-Martínez, ME; Déciga-Campos, M; Espinosa-Juárez, JV; Jaramillo-Morales, OA; López-Muñoz, FJ; Ventura-Martínez, R, 2023)	1.15
" The first dosage of study medicines was given intravenously 30 minutes (min) before surgery ended, followed by six hours (h) intervals for a total of eight doses following surgery."	( Analgesic Efficacy of Intravenous Ibuprofen in the Treatment of Postoperative Acute Pain: A Phase III Multicenter Randomized Placebo-ControlledDouble-Blind Clinical Trial. Li, TT; Liu, F; Pi, Y; Wang, TH; Xiong, LL; Zhou, HS, 2023)	0.91
" After the addition of magnesium sulfate, the analgesic effect was dramatically prolonged, leading to a reduction in morphine dosage within 24 h and the total morphine dosage postoperatively."	( Effects of magnesium sulfate on periarticular infiltration analgesia in total knee arthroplasty: a prospective, double-blind, randomized controlled trial. Chen, L; Kang, P; Wang, L; Wang, Q; Zhao, C, 2023)	1.12
" The dosage of the capsule, the temperature of the dissolving water and the type of filter used have been identified as the parameters most likely to influence the final quantity of morphine in solution before intravenous injection."	( Intravenous misuse of slow-release oral morphine capsules: how much morphine is injected? Authier, N; Bertin, C; Ferrer, F; Lauwerie, L; Montigne, E; Richard, D; Teixeira, S, 2023)	1.37
"Different morphine syringes were prepared by varying the dosage of the capsule (100 or 200 mg), the temperature of the dissolving water before adding morphine, ambient (≈ 22 °C) or heat (≈ 80 °C) and four filtration devices: risk reduction Steribox® cotton, risk reduction filter "Sterifilt®", "Wheel" filter and cigarette filter."	( Intravenous misuse of slow-release oral morphine capsules: how much morphine is injected? Authier, N; Bertin, C; Ferrer, F; Lauwerie, L; Montigne, E; Richard, D; Teixeira, S, 2023)	1.58
" Offering an injectable substitution to persons who inject morphine would make it possible to reduce the risks and damage, particularly overdoses, associated with variations in dosage due to preparation methods."	( Intravenous misuse of slow-release oral morphine capsules: how much morphine is injected? Authier, N; Bertin, C; Ferrer, F; Lauwerie, L; Montigne, E; Richard, D; Teixeira, S, 2023)	1.42
"Participants were randomly assigned (2:1) to daily dosing with ASP8062 25 mg or placebo on days 1-10."	( A phase 1 randomized, placebo-controlled study to investigate potential interactions between ASP8062, a positive allosteric modulator of the GABA Alsharif, MN; Blahunka, P; Blauwet, MB; Erdman, J; Heo, N; Ito, M; Kelsh, D; Marek, GJ; Spence, A; Walzer, M, 2023)	0.91
", i) the analgesic agent is identical to the OAT medication, and ii) the opioid agent is dosed above 1/6th morphine equivalent dose of the OAT medication."	( Rescue Analgesia for Opioid-Dependent Individuals on Opioid Agonist Treatment during Hospitalization: Adherence to Guideline Treatment. Arnet, I; Dürsteler, KM; Grossmann, F; Hersberger, KE; Jaiteh, C, 2023)	1.12
" This quality improvement project describes an EHR intervention to reduce daily dosing in opioid prescriptions in 11 emergency departments (ED) across the largest safety net health system in the US."	( Reducing daily dosing in opioid prescriptions in 11 safety net emergency departments. Alaiev, D; Alarcon, P; Chandra, K; Cho, HJ; Garcia, M; Krouss, M; Shin, D; Talledo, J; Tsega, S; Zaurova, M, 2023)	0.91
"In this prospective cohort study with comparisons to a historical control group, 24 patients were prospectively enrolled to receive an intraosseous infusion of morphine and ketorolac dosed according to age-based protocols while undergoing total knee arthroplasty."	( A multimodal intraosseous infusion of morphine and ketorolac decreases early postoperative pain and opioid consumption following total knee arthroplasty. Clyburn, TA; Incavo, SJ; Lambert, BS; Laurita, J; McNamara, CA; Park, KJ; Sullivan, TC, 2023)	1.38
"Our multimodal intraosseous infusion of morphine and ketorolac dosed according to age-based protocols improved immediate postoperative pain levels and reduced opioid consumption in the immediate postoperative period for patients undergoing total knee arthroplasty."	( A multimodal intraosseous infusion of morphine and ketorolac decreases early postoperative pain and opioid consumption following total knee arthroplasty. Clyburn, TA; Incavo, SJ; Lambert, BS; Laurita, J; McNamara, CA; Park, KJ; Sullivan, TC, 2023)	1.45
"Previous evaluations of medication dosing variance for children in the prehospital setting have been limited regionally or to specific conditions."	( Deviation From National Dosing Recommendations for Children Having Out-of-Hospital Emergencies. Martin-Gill, C; Ramgopal, S, 2023)	0.91
" We investigated dosing deviations (defined as being ≥20% of the weight-appropriate dose from national guidelines) for the following: lorazepam, diazepam, and midazolam for seizures; fentanyl, hydromorphone, morphine, and ketorolac; intramuscular epinephrine and diphenhydramine for children with allergy or anaphylaxis; intravenous epinephrine; and methylprednisolone."	( Deviation From National Dosing Recommendations for Children Having Out-of-Hospital Emergencies. Martin-Gill, C; Ramgopal, S, 2023)	1.1
" Appropriate dosing was most common with methylprednisolone (75."	( Deviation From National Dosing Recommendations for Children Having Out-of-Hospital Emergencies. Martin-Gill, C; Ramgopal, S, 2023)	0.91
"We identified variance in weight-based dosing from national guidelines for common pediatric medications in the prehospital setting, which may be attributable to protocol differences or dosing errors."	( Deviation From National Dosing Recommendations for Children Having Out-of-Hospital Emergencies. Martin-Gill, C; Ramgopal, S, 2023)	0.91
" Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted."	( Pharmacological agents for prevention of pruritus in women undergoing Caesarean delivery with neuraxial morphine: a systematic review and Bayesian network meta-analysis. Blake, L; Carvalho, B; Monks, DT; O'Carroll, J; Singh, NP; Singh, PM; Sultan, P, 2023)	1.12
" Additionally, both systemic and intra-insular administration of nicotine produces a rightward shift in the dose-response function in both morphine-induced conditioned place preference and taste avoidance paradigms, particularly at higher doses (5-20 mg/kg)."	( Nicotine limits avoidance conditioning with opioids without interfering with the ability to discriminate an opioid-interoceptive state. Ezenwa, KB; Gilles-Thomas, EA; Honeycutt, SC; Loney, GC; McSain, SL; Mukherjee, A; Paladino, MS; Sontate, KV, 2023)	1.11
"Optimal intrathecal dosing regimens for hydromorphone are not well established for analgesia after abdominal surgery."	( Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. Charnin, JE; Nuttall, GA; Portner, ER; Schroeder, DR; Sviggum, HP; Weingarten, TN, 2023)	0.91
"We reviewed intrathecal hydromorphone doses and complications because dosing variability has been observed among anesthesiologists."	( Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. Charnin, JE; Nuttall, GA; Portner, ER; Schroeder, DR; Sviggum, HP; Weingarten, TN, 2023)	0.91
" Patients were categorized into 3 hydromorphone dosing groups: low-dose (50-100 µg), middle-dose (101-199 µg), and high-dose (200-300 µg)."	( Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. Charnin, JE; Nuttall, GA; Portner, ER; Schroeder, DR; Sviggum, HP; Weingarten, TN, 2023)	0.91
" Higher rates of severe opioid-related events were detected for patients receiving high-dose hydromorphone in the PACU, but all other safety outcomes were similar between dosing regimens."	( Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications. Charnin, JE; Nuttall, GA; Portner, ER; Schroeder, DR; Sviggum, HP; Weingarten, TN, 2023)	0.91
" The intraoperative remifentanil dosage was significantly greater in groups M and C than in group B (P<0."	( Comparison of intrathecal low-dose bupivacaine and morphine with intravenous patient control analgesia for postoperative analgesia for video-assisted thoracoscopic surgery. Guo, M; Liu, F; Tang, S; Wang, L; Wang, Y; Yang, D; Zhang, J, 2023)	1.16