nicotine

Research Excerpts

Overview

Nicotine is a main constituent of cigarette smoke and smokeless tobacco. It is known to increase the risk of sudden cardiac death. Nicotine pouches are a relatively new type of oral smokeless tobacco-free nicotine product.

Excerpt	Reference	Relevance
"Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. "	( Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current. Nattel, S; Pourrier, M; Shi, H; Wang, H; Wang, Z; Yang, B; Zhang, L, 2000)	3.19
"Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. "	( Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current. Nattel, S; Pourrier, M; Shi, H; Wang, H; Wang, Z; Yang, B; Zhang, L, 2000)	3.19
"Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of α4β2-preferring nAChRs. "	( Neonicotinic analogues: selective antagonists for α4β2 nicotinic acetylcholine receptors. Adasme-Carreño, F; Alzate-Morales, J; Bermudez, I; Etcheverry-Berrios, A; Farias-Rabelo, N; Faundez-Parraguez, M; Gonzalez-Gutierrez, JP; Iturriaga-Vasquez, P; Varas, R, 2013)	1.83
"Nicotine is an addictive ingredient of tobacco products and other noncigarette substitutes, including those being used for smoking cessation to relieve withdrawal symptoms. "	( Nicotine causes alternative polarization of macrophages via Src-mediated STAT3 activation: Potential pathobiological implications. Acharya, S; Deshmukh, SK; Khan, MA; Saranyutanon, S; Singh, AP; Singh, S, 2022)	3.61
"Nicotine is an important risk factor and the main toxic component associated with periodontitis. "	( Nicotine regulates autophagy of human periodontal ligament cells through α7 nAchR that promotes secretion of inflammatory factors IL-1β and IL-8. Chen, Y; Du, Y; Ge, X; Wang, L; Wang, X; Wu, L; Yang, K; Zhou, Z, 2021)	3.51
"Nicotine is an endocrine disruptor and imprinting factor during breastfeeding that can cause food intake imbalance in the adulthood. "	( Changes in gut-brain axis parameters in adult rats of both sexes with different feeding pattern that were early nicotine-exposed. Atella, GC; Cabral, SS; Daleprane, JB; Kluck, GEG; Lisboa, PC; Lopes, BP; Manhães, AC; Moura, EG; Oliveira, E; Peixoto, TC; Rodrigues, VST; Soares, PN; Trindade, PL, 2021)	2.28
"Nicotine pouches (NPs) are a relatively new type of oral smokeless tobacco-free nicotine product. "	( A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette. Azzopardi, D; Camacho, OM; Fearon, IM; Gale, N; Hardie, G; McEwan, M; Murphy, J, 2022)	2.44
"Nicotine is a significant evaluation index of tobacco and its related products' quality, but nicotine overdose can pose serious health hazards and cause addiction and dependence, thus it can be seen that it is necessary to find suitable and efficient detection methods to precisely detect nicotine in diverse samples and complex matrices. "	( Nicotine in Complex Samples: Recent Updates on the Pretreatment and Analysis Method. Feng, XS; Liu, ZF; Tao, XY; Zhang, Y; Zhou, Y, 2023)	3.8
"Nicotine dependence is a dynamic process that is not limited to physical dependence."	( Comparison of withdrawal symptom intensity between hypnosis and nicotine-replacement-therapies: A pilot study. Girard, M; Lacroix, A; Lourmière, G; Nubukpo, P, 2022)	1.68
"Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. "	( Developmental nicotine exposure and masculinization of the rat preoptic area. Cauley, M; Corcoran, DL; Joglekar, R; Levin, ED; Lipsich, T; McCarthy, MM; Meyer, JN; Murphy, SK; Patisaul, HB, 2022)	2.52
"Nicotine is a harmful pollutant mainly from the waste of tobacco factories. "	( Nicotine metabolism pathway in bacteria: mechanism, modification, and application. He, Z; Hu, T; Mei, C; Mei, X; Shu, M; Xie, X; Xue, D; Yang, Y; Zhang, Z; Zhong, W, 2022)	3.61
"Nicotine exposure is a health concern not only for adults but also has neurotoxic effects on the fetus, newborn, child, and adolescent."	( Unique effects of nicotine across the lifespan. Leslie, F; Lotfipour, S; Ren, M, 2022)	1.78
"Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. "	( Assessing combined effects of varenicline and N-acetylcysteine on reducing nicotine seeking in rats. Beloate, LN; Doolittle, J; Froeliger, B; Garcia-Keller, C; Kalivas, PW; Meyerink, ME; Nall, RW; Penaloza, T, 2022)	2.39
"Nicotine is an addictive and poisonous agent. "	( Managing intoxications with nicotine-containing e-liquids. Dekkers, BGJ; Henstra, C; Olgers, TJ; Ter Maaten, JC; Touw, DJ, 2022)	2.46
"Nicotine is a dependence-producing component in electronic cigarettes. "	( Emission and Gas/Particle Partitioning Characteristics of Nicotine in Aerosols for Electronic Cigarettes. Gao, N; Gao, Y; Li, D; Wu, J, 2022)	2.41
"Nicotine use continues to be a major public health concern, with an alarming recent rise in electronic cigarette consumption. "	( Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies. Goldberg, LR; Gould, TJ, 2022)	2.46
"Oral nicotine pouches are a new form of tobacco-free nicotine products launched in recent years with a variety of flavors."	( Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. Li, D; Mayne, RG; McIntosh, S; Ossip, DJ; Rahman, I; Shao, Y; Xie, Z; Zou, J, 2022)	1.56
"Nicotine is a toxic alkaloid known to be responsible for the addictive feature of cigarettes. "	( CYP2A6 gene polymorphism and severity of coronary atherosclerosis in Indonesian male smokers: A pilot study. Aspar Mappahya, A; Mappangara, I; Qanitha, A; Yusuf, I, 2022)	2.16
"Nicotine addiction is a public health problem. "	( Acute pain after digital crushing and nicotine intoxication. Cigarettes are always a false friend. A prospective study. Bigorre, N; Brunet, J; Cesari, B; Gomez, M; Jeudy, J; Petit, A; Rabarin, F; Raimbeau, G; Saint-Cast, Y, 2023)	2.62
"Nicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. "	( Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers. Adams-Haduch, J; Chen, G; Khor, CC; Koh, WP; Lazarus, P; Nelson, HH; Perez-Paramo, YX; Thomas, CE; Wang, R; Watson, CJW; Yuan, JM, 2023)	2.63
"Nicotine is an addictive compound that interacts with nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA), inducing a release of dopamine in the nucleus accumbens (NAc). "	( ERK signaling is required for nicotine-induced conditional place preference by regulating neuroplasticity genes expression in male mice. Chen, H; Fan, L; Hou, H; Hu, Q; Liu, Y, 2023)	2.64
"Nicotine is a highly addictive substance that can cause teratogenic impacts in the embryo through redox-dependent pathways. "	( Mitigation of nicotine-induced developmental effects by 24-epibrassinolide in zebrafish. Félix, L; Monteiro, SM; Pereira, A; Pereira, F; Venâncio, C, 2023)	2.71
"Nicotine addiction is a neuropsychiatric disorder with dysfunction in cortices as well as white matter (WM). "	( Altered white matter functional network in nicotine addiction. Chen, Y; Fan, C; Gou, H; Hong, W; Liu, Y; Lv, W; Pan, Y; Ren, J; Song, H; Wang, Y; Wei, Z; Zha, R; Zhang, P; Zhang, X; Zhou, Y, 2023)	2.62
"Nicotine is a psychostimulant drug with purported use in sports environments, though the use of nicotine among athletes has not been studied extensively."	( Should We be Concerned with Nicotine in Sport? Analysis from 60,802 Doping Control Tests in Italy. Abate, MG; Botrè, F; Mündel, T; Peiró, AM; Zandonai, T, 2023)	2.65
"Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). "	( Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors. Aşkın, Cİ; Fincan, GSÖ; İlhan, SÖ; Kibar, AK; Koç, DS; Okçay, Y; Sarıoğlu, Y; Vural, İM, 2022)	2.49
"Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. "	( Preparation and Evaluation of Liposomes Containing Ethanol and Propylene Glycol as Carriers for Nicotine. Cui, P; Dai, Z; Ding, J; Ma, L; Shao, Q; Wang, H; Wang, W; Yang, L; Yang, M; Zhang, Y, 2024)	3.1
"Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., "vaping") and nicotine e-liquids containing additives with rich chemosensory properties. "	( Strawberry Additive Increases Nicotine Vapor Sampling and Systemic Exposure But Does Not Enhance Pavlovian-Based Nicotine Reward in Mice. De Biasi, M; Dossat, AM; Dreier, A; Johnson, NL; Kimball, BA; Patten, T; Shaw, JK; Wesson, DW, 2023)	2.64
"Nicotine is a common indoor air pollutant that is present in cigarette fumes. "	( Nicotine exposure disrupts placental development via the Notch signaling pathway. Miao, YL; Sun, QR; Wu, DY; Wu, LH; Zhang, JJ; Zhang, X; Zhou, J, 2023)	3.8
"Nicotine is an addictive chemical." This exploratory study aims to inform potential future investigations and FDA decisions regarding alternative warnings that may generate fear in addition to being intentionally informational."	( Perceived threat and fear responses to e-cigarette warning label messages: Results from 16 focus groups with U.S. youth and adults. Avery, RJ; Byrne, S; Dorf, M; Kalaji, M; Mathios, A; Niederdeppe, J; Safi, AG, 2023)	1.63
"Like nicotine, cytisine is a plant alkaloid, signaling through nicotinic acetylcholine receptors."	( Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model. Budzyńska, B; Chałas, R; Maciąg, M; Rahnama-Hezavah, M; Stachurski, P; Świątkowska, A; Świątkowski, W; Tylżanowski, P, 2023)	2.81
"Nicotine use is a continuing public health concern. "	( Effects of acute and chronic nicotine administration on probability discounting. Anderson, KG; Nolder, KA, 2023)	2.64
"Nicotine is an addictive substance often found in tobacco and cigarette smoke and excessive exposure to it can cause various diseases. "	( A core-molecule-shell Au@PATP@Ag nanorod for nicotine detection based on surface-enhanced Raman scattering technology. Chen, Y; Li, P; Sun, S; Tang, Y; Wang, D; Wang, Y; Wei, W; Zhuang, Y, 2023)	2.61
"Nicotine (NIC) is a harmful substance, drug, pesticide and chemical that is widely found in tobacco. "	( A colorimetric sensor with dual-ratio and dual-mode for detection of nicotine in tobacco samples. Cheng, C; Hu, S; Li, J; Liang, P; Song, H; Su, Z; Wang, J; Yu, X; Zhao, Y, 2023)	2.59
"Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. "	( Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ-Adiponectin-AdipoR1 Axis. Abd Rami, AZ; Aminuddin, A; Hamid, AA; Mokhtar, MH; Ugusman, A, 2023)	3.8
"Nicotine is a naturally occurring and highly addictive chemical used in e-cigarettes, cigarettes, chewing tobacco, and other tobacco products as well as in nicotine replacement therapies. "	( Quantitation of Urine Nicotine, Cotinine, and 3-OH-Cotinine by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Li, W; Noguez, J; Zhang, XS, 2024)	3.2
"Nicotine vaccines are an attractive alternative to the current smoking cessation options but have yet to be successful enough in clinical trials to reach the market due to a lack of neutralizing antibodies and inconsistent results."	( Assessing the immunogenicity and toxicity of the AFPL1-conjugate nicotine vaccine using heterologous and homologous vaccination routes. Acevedo, R; Dagmar, GR; Fraleigh, NL; Le, HT; Lewicky, JD; Martel, AL; Oliva, R, 2019)	1.47
"The nicotine delivery rate is a key feature of tobacco product design, yet there have been limited human studies examining the effects of nicotine as a function of delivery rate."	( Differential effects of nicotine delivery rate on subjective drug effects, urges to smoke, heart rate and blood pressure in tobacco smokers. Gueorguieva, R; Jensen, KP; Sofuoglu, M; Valentine, G, 2020)	1.42
"Nicotine is a major tobacco component and found at circulating concentrations in smokers' bloodstreams. "	( Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance. Avraham, H; Chen, C; Ganapathy, S; Nishioka, T; Zhang, Q, 2020)	3.44
"Nicotine appears to be a mechanistic treatment for this specific disorder, probably because of desensitization of the mutated receptors. "	( Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Bjørnvold, M; Brodtkorb, E; Chelly, J; de Saint Martin, A; Lossius, K; Minken, G; Myren-Svelstad, S; Picard, F; Seegmuller, C; Steinlein, O; Valenti Hirsch, MP, 2020)	2.28
"Nicotine is proved to be an important factor for cardiac hypertrophy. "	( Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop. Ge, D; Hu, KQ; Li, M; Li, Y; Ma, XL; Meng, FL; Meng, TT; Ni, X; Su, GH; Wang, SY; Wu, HH; Zhao, J, 2020)	2.32
"Nicotine is an addictive compound that activates neuronal nicotinic acetylcholine receptors (nAChRs) and causes behavioural effects that vary with dose, schedule of administration, and animal model. "	( Opposing effects of acute and repeated nicotine exposure on boldness in zebrafish. Dean, R; Duperreault, E; Franczak, BC; Gallup, J; Hamilton, TJ; Ingraham, E; Krook, J; Newton, D, 2020)	2.27
"Nicotine is a stimulant and potent parasympathomimetic alkaloid that accounts for 96-98% of alkaloid content. "	( Reducing the nicotine content of tobacco by grafting with eggplant. Ren, M; Shi, H; Yang, H; Zhang, M, 2020)	2.37
"Nicotine is a psychoactive substance involved in numerous neuronal processes including cortical excitability."	( The Effects of Nicotine on Cortical Excitability After Exercise: A Double-Blind Randomized, Placebo-controlled, Crossover Study. Bruseghini, P; Cesari, P; Chiamulera, C; Pizzolato, F; Tam, E; Zandonai, T, )	1.21
"Nicotine is a highly addictive drug found in tobacco that drives its continued use despite the harmful consequences. "	( Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction. Dani, JA; De Biasi, M; Wittenberg, RE; Wolfman, SL, 2020)	2.27
"Nicotine is an alkaloid and a secondary plant metabolite that has been used as an insecticide. "	( Validation and measurement uncertainty of GC-MS quantification method for nicotine in dried mushrooms using QuEChERS extraction. Kang, HH; Kim, YJ; Lee, JG; Moon, JY; Yun, CI, 2020)	2.23
"Nicotine is a potent psychostimulant with a high addiction liability that can significantly alter brain function."	( Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration. Bevins, RA; Chand, S; Guda, C; Koul, S; Kumar, V; Nanoth Vellichirammal, N; Pendyala, G; Pittenger, ST; Schaal, VL; Yelamanchili, SV, 2020)	1.5
"Nicotine is a toxic environmental pollutant that widely exists in tobacco wastes. "	( Differential Effects of Homologous Transcriptional Regulators NicR2A, NicR2B1, and NicR2B2 and Endogenous Ectopic Strong Promoters on Nicotine Metabolism in Chen, Z; He, Z; Huang, C; Jiao, Y; Li, J; Linhardt, RJ; Pan, F; Shan, L; Shu, M; Yang, Y; Zhang, F; Zhong, W, 2021)	2.27
"Nicotine is an important emerging contaminant widely detected in water resources. "	( UV-254 degradation of nicotine in natural waters and leachates produced from cigarette butts and heat-not-burn tobacco products. Alberti, S; Fernández, E; Ferretti, M; Psillakis, E; Solomou, N; Sotiropoulou, M, 2021)	2.38
"Nicotine is a major constituent of cigarette smoke. "	( Nicotine and Its Downstream Metabolites in Maternal and Cord Sera: Biomarkers of Prenatal Smoking Exposure Associated with Offspring DNA Methylation. Anthony, TM; Arshad, H; Commodore, S; Eslamimehr, S; Ewart, S; Holloway, JW; Jones, AD; Karmaus, W; Kheirkhah Rahimabad, P; Mukherjee, N, 2020)	3.44
"Nicotine is an active pharmacological ingredient in cigarette smoke, which may negatively influence the male reproductive system and fertility. "	( Ameliorative effect of fractionated low-dose gamma radiation in combination with ellagic acid on nicotine-induced hormonal changes and testicular toxicity in rats. Abdel-Naby, DH; Ashoub, AH; El-Ghazaly, MA; Kenawy, SA; Safar, MM, 2021)	2.28
"Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine in different regions of the brain. "	( Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity. Aryal, SP; Fu, X; Grady, ME; Lakes, JE; Neupane, KR; Richards, CI; Sandin, JN, 2021)	3.51
"Nicotine is a prominent active compound in tobacco and many smoking cessation products. "	( Temporal proteomic changes induced by nicotine in human cells: A quantitative proteomics approach. Gygi, SP; Navarrete-Perea, J; Paulo, JA, 2021)	2.34
"Nicotine is a cholinergic agonist and is the principal psychoactive compound in tobacco linked to cigarette addiction."	( Nicotine suppresses Parkinson's disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Campusano, JM; Carvajal-Oliveros, A; Domínguez-Baleón, C; Narváez-Padilla, V; Reynaud, E; Zárate, RV, 2021)	2.79
"Nicotine addiction is a leading avoidable brain disorder globally. "	( Activation of trace amine-associated receptor 1 attenuates nicotine withdrawal-related effects. Huang, Y; Johnson, B; Li, JX; Liu, J; Wu, R; Zhang, Y, 2022)	2.41
"Nicotine exposure is a major risk factor for several cardiovascular diseases. "	( Nicotine Affects Murine Aortic Stiffness and Fatigue Response During Supraphysiological Cycling. Ho, E; Lee, SJ; Mulorz, J; Ramasubramanian, AK; Tsao, PS; Wagenhäuser, MU; Wong, J, 2022)	3.61
"Nicotine is an addictive substance historically consumed through smoking and more recently through the use of electronic vapor devices. "	( Electronic Nicotine Vapor Exposure Produces Differential Changes in Central Amygdala Neuronal Activity, Thermoregulation and Locomotor Behavior in Male Mice. Cole, M; Douglass, EA; Echeveste Sanchez, M; Esther, CR; Guhr Lee, TN; Hanback, TD; Herman, MA; Jahad, JV; Roberts, AJ; Zhu, M, )	1.96
"Nicotine is a cholinergic agonist and pro-inflammatory cytokines inhibitor. "	( The smoker's paradox during the COVID-19 pandemic? The influence of smoking and vaping on the incidence and course of SARS-CoV-2 virus infection as well as possibility of using nicotine in the treatment of COVID-19 - Review of the literature. Bilska, M; Korzeniowska, A; Piecewicz-Szczęsna, H; Ręka, G, 2021)	2.26
"Nicotine is a strong psychoactive and addictive compound found in tobacco. "	( Developmental nicotine exposure impairs memory and reduces acetylcholine levels in the hippocampus of mice. Gavini, K; Parameshwaran, K; Yang, E, 2021)	2.42
"Nicotine is an alkaloid which only highly exists in tobacco plants. "	( Impact of exogenous nicotine on the morphological, physio-biochemical, and anatomical characteristics in Abdo, N; Alkhatib, B; Alkhatib, R, 2022)	2.49
"Nicotine is a "life-style compound" widely consumed by human populations and, consequently, often found in surface waters. "	( Toxic potential of the emerging contaminant nicotine to the aquatic ecosystem. Floro, AM; Oropesa, AL; Palma, P, 2017)	2.16
"Nicotine (Nic) is a major risk factor in the development of functional disorders of male reproductive system. "	( Ameliorative effects of Achillea millefolium inflorescences alcoholic extract against nicotine-induced reproductive failure in rat. Hasanzadeh, S; Malekinejad, H; Salahipour, MH, 2017)	2.12
"Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology."	( Revisiting nicotine's role in the ageing brain and cognitive impairment. Kamari, F; Majdi, A; Sadigh-Eteghad, S; Vafaee, MS, 2017)	1.57
"Nicotine is a major biologically active component in cigarette smoke."	( Disruption of retinal pigment epithelial cell properties under the exposure of cotinine. Brelén, ME; Cao, D; Chan, KP; Chan, SO; Ng, TK; Pang, CP; Wang, Y; Wu, D; Yung, JSY; Zhang, S; Zhang, XY, 2017)	1.18
"Nicotine is a natural component of tobacco plants and is responsible for the addictive properties of tobacco. "	( Protective effects of quercetin on nicotine induced oxidative stress in 'HepG2 cells'. Bolouki, A; Yarahmadi, A; Zal, F, 2017)	2.17
"Nicotine acts as an agonist at presynaptic nicotinic acetylcholine receptors and to facilitate synaptic release of several neurotransmitters including dopamine and glutamate. "	( Reduced Thalamus Volume May Reflect Nicotine Severity in Young Male Smokers. Bi, Y; Cheng, J; Guan, Y; Li, Y; Liu, B; Lu, X; Luo, L; Xue, T; Yu, D; Yuan, K; Zhai, J, 2018)	2.2
"Nicotine is a psychoactive substance that is commonly consumed in the context of music. "	( Nicotine enhances an auditory Event-Related Potential component which is inversely related to habituation. Overton, PG; Taroyan, N; Veltri, T, 2017)	3.34
"Nicotine addiction is an issue faced by millions of individuals worldwide. "	( Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch. Linakis, MW; Miller, EI; Roberts, JK; Rower, JE; Sherwin, CMT; Wilkins, DG, 2017)	2.15
"Nicotine is a highly toxic tobacco alkaloid that is ubiquitous in wastewater effluent. "	( Photochemical Transformation of Nicotine in Wastewater Effluent. Chan, SA; Lian, L; Song, W; Yan, S; Yao, B, 2017)	2.18
"Nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs), and mecamylamine, a nonselective nAChR antagonist, attenuates effects of nicotine on delay discounting in some rat strains; whether nicotine's attenuation is specific to nAChR antagonism is unknown."	( Reduction in delay discounting due to nicotine and its attenuation by cholinergic antagonists in Lewis and Fischer 344 rats. Anderson, KG; Ozga, JE, 2018)	2.19
"As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages."	( Microglia Activation and Gene Expression Alteration of Neurotrophins in the Hippocampus Following Early-Life Exposure to E-Cigarette Aerosols in a Murine Model. Aschner, M; Corbett, K; Gordon, T; Klein, CB; Parmalee, NL; Zelikoff, JT, 2018)	0.99
"Nicotine is a psychostimulant that is reported to be commonly supplemented by athletes. "	( Effect of nicotine on repeated bouts of anaerobic exercise in nicotine naïve individuals. Crowe, M; Doma, K; Johnston, R, 2018)	2.33
"Nicotine is a major addictive compound in tobacco and a component of smoking-related products, such as e-cigarettes. "	( Multiplexed Isobaric Tag-Based Profiling of Seven Murine Tissues Following In Vivo Nicotine Treatment Using a Minimalistic Proteomics Strategy. Chouchani, ET; Gygi, SP; Jedrychowski, MP; Kazak, L; Paulo, JA, 2018)	2.15
"Nicotine is a dangerous substance extracted from tobacco leaves. "	( Symptomatic bradycardia due to nicotine intoxication. Durey, A; Kang, S; Kim, AJ; Kim, JH; Paik, JH, 2018)	2.21
"Nicotine is an alkaloid with positive effects on learning and memory processes. "	( Nicotine increases fear responses and brain acetylcholinesterase activity in a context-dependent manner in zebrafish. Canzian, J; Duarte, T; Fontana, BD; Müller, TE; Rosemberg, DB; Stefanello, FV; Ziani, PR, 2018)	3.37
"Nicotine is a major toxic alkaloid in wastes generated from tobacco production and cigarette manufacturing. "	( Characterization of Nicotine Catabolism through a Novel Pyrrolidine Pathway in Pseudomonas sp. S-1. Cao, H; Hua, R; Li, QX; Lv, P; Pan, D; Sun, M; Wang, Y; Wu, X, 2018)	2.25
"Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are "safer" than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking."	( Nicotine and the renin-angiotensin system. Fuchs, RM; Gardner, JD; Lazartigues, E; Oakes, JM; Yue, X, 2018)	2.64
"Nicotine is an important factor in the pathogenesis of renal injury in smokers."	( Renoprotective effect of Spirulina platensis extract against nicotine-induced oxidative stress-mediated inflammation in rats. Emam, MA; Zahran, WE, 2018)	2.16
"Nicotine is an addictive drug that has broad effects throughout the brain. "	( Effects of acute and chronic nicotine on catecholamine neurons of the nucleus of the solitary tract. Appleyard, SM; Page, SJ; Zhu, M, 2019)	2.25
"Nicotine is a major biologically active constituent of tobacco products."	( Roles of Nicotine in the Development of Intracranial Aneurysm Rupture. Furukawa, H; Hashimoto, T; Kamio, Y; Kimura, T; Korai, M; Kudo, D; Lawton, MT; Lukas, RJ; Mitsui, K; Miyamoto, T; Yokosuka, K; Zhang, D, 2018)	1.62
"Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. "	( Acute pulmonary effects of aerosolized nicotine. Ahmad, A; Ahmad, S; Eltoum, IA; Husain, M; Mariappan, N; Vetal, N; Wei, CC; Zafar, I, 2019)	2.23
"Nicotine is an important indicator in the quality evaluation of tobacco and its related products. "	( [Advances in nicotine pretreatment and determination method]. Meng, Z; Wei, T; Xue, M; Zhang, J, 2018)	2.29
"Nicotine is a bioactive molecule that acts upon nicotinic acetylcholine receptors expressed on neuronal and non-neuronal cells including endothelial cells."	( Nicotine Modulates Growth Factors and MicroRNA to Promote Inflammatory and Fibrotic Processes. Bonnen, MD; Ebrahimpour, A; Eissa, NT; Ghebre, YT; Raghu, G; Shrestha, S, 2019)	2.68
"Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. "	( Nephroprotective and antioxidant effect of green tea ( Ben Saad, A; Ncib, S; Rjeibi, I; Saidi, I; Zouari, N, 2019)	1.96
"Nicotine is an alkaloid that affects the functioning of the central nervous system and produces dependence. "	( Prolonged exposure to transdermal nicotine improves memory in male mice, but impairs biochemical parameters in male and female mice. Borzęcki, A; Nieradko-Iwanicka, B; Pietraszek, D; Pośnik, K, 2019)	2.24
"Nicotine is a component of cigarette smoke and mounting evidence suggests toxicity and carcinogenicity of tobacco smoke in kidney. "	( Nicotine-induced oxidative stress contributes to EMT and stemness during neoplastic transformation through epigenetic modifications in human kidney epithelial cells. Chang, YW; Singh, KP, 2019)	3.4
"Nicotine is a major toxic component of cigarette smoke and a major risk factor for functional disorders in the liver, because it induces oxidative stress."	( Harmine shows therapeutic activity on nicotine-induced liver failure in mice. Farokhi, M; Jalili, C; Mahmoudian, ZG; Roshankhah, S; Salahshoor, MR, 2019)	1.51
"Nicotine is a major component of tobacco plants and is responsible for the development of reproductive problems in smokers. "	( Nicotine-Induced Oxidative Stress in Human Primary Endometrial Cells. Khademi, F; Mohammadi, N; Totonchi, H; Zal, F; Zare, R, )	3.02
"Nicotine is a key toxic component of tobacco."	( MicroRNA expression profiling of nicotine-treated human periodontal ligament cells. Cheng, Y; Du, A; Wei, X; Zhao, S; Zhou, Y, 2019)	1.52
"Nicotine is a natural alkaloid present in the tobacco plant which has been well studied as a constituent of cigarette smoke."	( Mitochondria as a possible target for nicotine action. Drabik, K; Duszyński, J; Hoeng, J; Luettich, K; Malińska, D; Mathis, C; Michalska, B; Patalas-Krawczyk, P; Peitsch, MC; Prill, M; Szczepanowska, J; Szymański, J; Van der Toorn, M; Walczak, J; Więckowski, MR, 2019)	1.51
"Nicotine is an alkaloid and potent parasympathomimetic stimulant found in the leaves of many plants including Nicotiana tabacum, which functions as an anti-herbivore chemical and an insecticide. "	( Molecular sensor of nicotine in taste of Drosophila melanogaster. Lee, Y; Rimal, S, 2019)	2.28
"Nicotine is a toxicant of particular concern for pregnant women, as nicotine is known to harm a developing fetus."	( Electronic nicotine delivery systems and pregnancy: Recent research on perceptions, cessation, and toxicant delivery. Ashford, K; Breland, A; McCubbin, A, 2019)	1.63
"Nicotine content is an important factor in weighing the potential benefits and risks of e-cigarettes on individual and population level health."	( Patterns of nicotine concentrations in electronic cigarettes sold in the United States, 2013-2018. Cuccia, AF; Hair, EC; King, BA; Marynak, K; Miller Lo, EJ; Romberg, AR; Vallone, DM; Willett, JG; Xiao, H, 2019)	1.61
"Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. "	( The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex. Balkan, B; Gozen, O; Koylu, EO; Pogun, S; Yildirim, E, 2013)	2.14
"Nicotine is a psychoactive component of tobacco products that acts as does the natural neurotransmitter, acetylcholine, on nicotinic receptors (nAChRs)."	( Nicotinic receptor β2 determines NK cell-dependent metastasis in a murine model of metastatic lung cancer. Abdelwahab, M; Hao, J; Lukas, R; Shi, FD; Shi, SX; Simard, A; Whiteaker, P; Zhou, Q, 2013)	1.11
"Nicotine is a highly addictive substance, suggested to be in part due to its cognitive enhancing effects in the attentional domain. "	( Effects of nicotine on visuospatial attentional orienting in non-smokers. Chique-Alfonzo, M; Fisher, DJ; Impey, D; Knott, VJ; Shah, D, 2013)	2.22
"Nicotine is a widely used addictive drug, with an estimated 73 million Americans 12 years of age or older having used a tobacco product in the last month, despite documented risks to personal health. "	( The effects of acute nicotine, chronic nicotine, and withdrawal from chronic nicotine on performance of a cued appetitive response. Cordero, KA; Gould, TJ; Leach, PT, 2013)	2.15
"Nicotine addiction is a serious health problem resulting in millions of preventable deaths worldwide. "	( Brain nitric oxide metabolites in rats preselected for nicotine preference and intake. Kanit, L; Keser, A; Nesil, T; Pogun, S, 2013)	2.08
"Nicotine is an alkaloid present in many plants of Solanaceae family. "	( [Absorption, metabolism and excretion of nicotine in humans]. Lesicki, A; Sobkowiak, R, 2013)	2.1
"Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. "	( Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study. Bavarva, JH; Garner, HR; Settlage, RE; Tae, H, 2013)	2.11
"Nicotine is a chiral compound and consequently exists as two enantiomers. "	( (R)-nicotine biosynthesis, metabolism and translocation in tobacco as determined by nicotine demethylase mutants. Bush, LP; Cai, B; Dewey, RE; Jack, AM; Lewis, RS, 2013)	2.39
"Nicotine is a significant toxic waste generated in tobacco manufacturing. "	( Isolation, transposon mutagenesis, and characterization of the novel nicotine-degrading strain Shinella sp. HZN7. Hong, J; Liu, W; Ma, Y; Qiu, J; Wei, Y; Wen, R, 2014)	2.08
"Nicotine dependence is a serious public health concern. "	( Subjective, physiological, and cognitive responses to intravenous nicotine: effects of sex and menstrual cycle phase. DeVito, EE; Herman, AI; Sofuoglu, M; Valentine, GW; Waters, AJ, 2014)	2.08
"Nicotine is a very toxic plant natural compound, and its mode of action resembles that of synthetic neonicotinoids. "	( Adaptation to nicotine in the facultative tobacco-feeding hemipteran Bemisia tabaci. Ghanim, M; Jander, G; Kliot, A; Kontsedalov, S; Ramsey, JS, 2014)	2.21
"Nicotine dependence is a major cause of mortality and morbidity all over the world. "	( Pharmacological intervention of nicotine dependence. Gupta, T; Jain, R; Majumder, P, 2013)	2.12
"Nicotine is an addictive substance of tobacco. "	( Chronic administration of nicotine enhances NMDA-activated currents in the prefrontal cortex and core part of the nucleus accumbens of rats. Ávila-Ruiz, T; Carranza, V; Flores, G; Flores-Hernández, J; Gustavo, LL; Limón, DI; Martínez, I, 2014)	2.15
"Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. "	( Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations. Aso, E; Balerio, GN; Maldonado, R; Moutinho, LM; Varani, AP, 2014)	2.14
"Nicotine is a potent tool to augment this system, but most studies investigated its effects solely on behavior."	( The effect of enhancing cholinergic neurotransmission by nicotine on EEG indices of inhibition in the human brain. Böcker, KB; Deschamps, PK; Kemner, C; Kenemans, JL; Logemann, HN, 2014)	1.37
"Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. "	( Nicotine effects and the endogenous opioid system. Kiguchi, N; Kishioka, S; Kobayashi, Y; Saika, F, 2014)	3.29
"Nicotine is a natural alkaloid and insecticide in tobacco leaves. "	( Airborne nicotine concentrations in the workplaces of tobacco farmers. Kim, BS; Kim, IS; Kim, JS; Lee, K; Lim, HS; Park, SJ; Yoo, SJ, 2014)	2.26
"Nicotine is a compound of tobacco plants and is responsible for addictive properties of tobacco which is used by about one billion of smokers all over the world. "	( Nicotine impact on melanogenesis and antioxidant defense system in HEMn-DP melanocytes. Beberok, A; Buszman, E; Delijewski, M; Otręba, M; Rok, J; Wrześniok, D, 2014)	3.29
"Nicotine is an important environmental toxicant in tobacco waste. "	( A novel (S)-6-hydroxynicotine oxidase gene from Shinella sp. strain HZN7. Liu, W; Ma, Y; Qiu, J; Wei, Y; Wen, R; Wen, Y, 2014)	2.16
"Nicotine is a main alkaloid in tobacco and is also the primary toxic compound in tobacco wastes. "	( 6-hydroxy-3-succinoylpyridine hydroxylase catalyzes a central step of nicotine degradation in Agrobacterium tumefaciens S33. Huang, H; Li, H; Wang, S; Xie, K, 2014)	2.08
"Nicotine is a known analgesic. "	( Intranasal nicotine increases postoperative nausea and is ineffective in reducing pain following laparoscopic bariatric surgery in tobacco-Naïve females: a randomized, double blind trial. Kellogg, TA; Kendrick, ML; Liedl, L; McGlinch, BP; Schroeder, DR; Sprung, J; Weingarten, TN, 2015)	2.25
"Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. "	( Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes. Beberok, A; Buszman, E; Delijewski, M; Otręba, M; Rok, J; Wrześniok, D, 2014)	2.25
"Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. "	( The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats. Brianna Sheppard, A; Brown, RW; Kellicut, MR; Palmatier, MI; Robinson, DL, 2014)	2.12
"Nicotine is a major alkaloid found in tobacco products and its detection with its metabolites in human matrices is generally used for assessing tobacco consumption and second hand exposure."	( Recent advances in MS methods for nicotine and metabolite analysis in human matrices: clinical perspectives. El-Khoury, JM; Wang, S, 2014)	1.4
"Nicotine is an addictive alkaloid in cigarette smoke and is responsible for tobacco dependence. "	( Involvement of the H+/organic cation antiporter in nicotine transport in rat liver. Akanuma, S; Hosoya, K; Kubo, Y; Tega, Y, 2015)	2.11
"Nicotine is a terotogen, altering neuronal development of various neurotransmitter systems, and it is likely these alterations participate in postnatal deficits in attention control and facilitate development of drug addiction."	( Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention. Kohlmeier, KA, 2015)	2.58
"Nicotine is an important stimulant that is involved in modulating many neuronal processes, including those related to vision. "	( Small effects of smoking on visual spatiotemporal processing. Herzog, MH; Kunchulia, M; Pilz, KS, 2014)	1.85
"Nicotine is an active substance present in tobacco that causes oxidative stress and tissues damages leading to several diseases. "	( Nicotine-induced reproductive toxicity, oxidative damage, histological changes and haematotoxicity in male rats: the protective effects of green tea extract. Mantovani, A; Mosbah, R; Yousef, MI, 2015)	3.3
"Nicotine is a common contaminant found on indoor surfaces. "	( A pilot study on nicotine residues in houses of electronic cigarette users, tobacco smokers, and non-users of nicotine-containing products. Bush, D; Goniewicz, ML, 2015)	2.2
"Nicotine is an abundant and most significant component of cigarette smoke. "	( Synergistic protective effect of folic acid and vitamin B12 against nicotine-induced oxidative stress and apoptosis in pancreatic islets of the rat. Bhattacharjee, A; Maji, B; Mukherjee, S; Pal, S; Prasad, SK; Syamal, AK, 2016)	2.11
"Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. "	( Examining the reinforcement-enhancement effects of phencyclidine and its interactions with nicotine on lever-pressing for a visual stimulus. Barrett, ST; Bevins, RA; Li, M; Swalve, N, 2015)	2.08
"Nicotine addiction is a chronic brain disorder that is characterized by dysphoria upon smoking cessation and relapse after brief periods of abstinence. "	( Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats. Bruijnzeel, AW; Guzhva, L; Ji, Y; Qi, X, 2015)	2.07
"Nicotine acts as a cholinergic channel modulator, and its cognitive-enhancing effect in neurodegenerative and cognitive disorders has been documented."	( Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories. Cao, J; Chang, SL; Li, MD; Nesil, T; Yang, Z, 2015)	2.58
"Nicotine is a parasympathomimetic alkaloid present in tobacco which can induce hyperlipidemia and has a direct effect on neural functions. "	( Atorvastatin improves Y-maze learning behaviour in nicotine treated male albino rats. Das S, S; Febi, J; Indira, M; Kavitha, S; Nair, SS, 2015)	2.11
"Nicotine is a major psychoactive and addictive component of tobacco. "	( Cognitive control deficits during mecamylamine-precipitated withdrawal in mice: Possible links to frontostriatal BDNF imbalance. Cole, RD; Gould, TJ; Parikh, V; Patel, PJ; Poole, RL, 2016)	1.88
"Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco."	( Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications. D'Souza, MS, 2016)	1.5
"Nicotine is a potent addictive alkaloid, and is rapidly absorbed through the alveoli of the lung. "	( Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells. Akanuma, SI; Ehrhardt, C; Hosoya, KI; Kubo, Y; Tega, Y; Yuzurihara, C, 2016)	2.18
"Nicotine is a readily available potent poison."	( Development and validation of a GC-MS method for nicotine detection in Calliphora vomitoria (L.) (Diptera: Calliphoridae). Alladio, E; Brandimarte, M; Dadour, IR; Magni, PA; Pazzi, M; Vincenti, M, 2016)	1.41
"Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. "	( Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca Dong, K; Huang, J; Ju, JF; Li, N; Ning, YS; Qiao, B; Ren, J; Si, B; Wang, D; Wang, TJ; You, F; Yu, WQ; Zhang, FQ; Zhu, M, 2016)	3.32
"Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. "	( Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum. Goutier, W; Lowry, JP; McCreary, AC; O'Connor, JJ, 2016)	2.13
"Nicotine substitution is a mainstay component in smoking cessation schemes. "	( Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers. Drewe, J; Guercioni, S; Hammann, F; Imanidis, G; Kummer, O, 2016)	2.13
"Nicotine is a pharmacologically active component of the tobacco that adversely affects the male reproductive system and fertility. "	( Protective effect of Eruca sativa seed oil against oral nicotine induced testicular damage in rats. Abd El-Aziz, GS; El-Fark, MO; Hamdy, RM, 2016)	2.12
"Nicotine is a major toxic agent and has been associated with exacerbated inflammatory diseases."	( Nicotine induces neutrophil extracellular traps. Hosseinzadeh, A; Segal, BH; Thompson, PR; Urban, CF, 2016)	2.6
"Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. "	( The effect of simultaneous exposure of HEMn-DP and HEMn-LP melanocytes to nicotine and UV-radiation on the cell viability and melanogenesis. Beberok, A; Buszman, E; Delijewski, M; Otręba, M; Rok, J; Wrześniok, D, 2016)	2.11
"Nornicotine is a natural alkaloid produced by plants in the genus Nicotiana and is structurally related to nicotine. "	( Conversion of nornicotine to 6-hydroxy-nornicotine and 6-hydroxy-myosmine by Shinella sp. strain HZN7. He, J; Li, N; Liu, W; Lu, Z; Ma, Y; Niu, L; Qiu, J; Yang, Y, 2016)	1.4
"Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. "	( Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism. Balakrishna, S; Bonner, PE; Fan, L; Jabba, SV; Jordt, SE; Picciotto, MR; Taylor, SR, 2016)	2.19
"Nicotine is an exogenous agonist for acetylcholine receptors, suggesting that endogenous cholinergic signalling may play a part in normal physiological regulation of feeding."	( A cholinergic basal forebrain feeding circuit modulates appetite suppression. Arenkiel, BR; Carlson, JC; Herman, AM; Herman, I; Kochukov, M; Ortiz-Guzman, J; Patel, JM; Quast, KB; Selever, J; Tepe, B; Tong, Q; Ung, K, 2016)	1.16
"Nicotine is an environmental toxicant in tobacco wastes, imposing severe hazards for the health of human and other mammalians. "	( Structural basis for the transcriptional repressor NicR2 in nicotine degradation from Pseudomonas. Hu, C; Shi, T; Tang, H; Wu, G; Xu, P; Zhang, K, 2017)	2.14
"Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. "	( Protective effects of quercetin and vitamin C against nicotine-induced toxicity in the blood of Wistar rats. Matić, MM; Ognjanović, BI; Paunović, MG; Saičić, ZS; Štajn, AŠ, 2016)	2.13
"Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. "	( A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication. Helanterä, I; Kalliomäki, J; Lempinen, M; Parry, M; Räsänen, M; Savikko, J, )	1.81
"Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. "	( Effects of nicotine on response inhibition and interference control. Chan, RC; Ettinger, U; Faiola, E; Kasparbauer, AM; Kumari, V; Liepelt, R; Petrovsky, N, 2017)	2.29
"Nicotine dependence is a key barrier to smoking cessation. "	( Smoking characteristics and saliva cotinine levels in Taiwanese smokers: gender differences. Huang, CL; Lin, HH; Yang, YH, 2008)	1.79
"Nicotine is a major component of tobacco smoke, and signals via nicotinic acetylcholine receptors (nAChR). "	( Nicotine inhibits mineralization of human dental pulp cells. Kashiwagi, Y; Kobayashi, R; Murakami, S; Shimabukuro, Y; Tomoeda, M; Yanagita, M, 2008)	3.23
"Nicotine addiction is a complex, chronic condition with physiological and psychological/behavioural aspects that make smoking cessation extremely difficult. "	( Multimodal techniques for smoking cessation: a review of their efficacy and utilisation and clinical practice guidelines. Reus, VI; Smith, BJ, 2008)	1.79
"Nicotine is a primary constituent of tobacco and smoke, and its roles in causing addiction and causing disease are commonly conflated. "	( Reduced-nicotine cigarettes increase platelet activation in smokers in vivo: a dilemma in harm reduction. Bluestein, D; Girdhar, G; Jesty, J; Xu, S, 2008)	2.22
"Nicotine is a drug of abuse that has been reported to have many adverse effects on the developing nervous system. "	( Secondary motoneurons in juvenile and adult zebrafish: axonal pathfinding errors caused by embryonic nicotine exposure. Menelaou, E; Svoboda, KR, 2009)	2.01
"Nicotine is a pharmacologically active substance and potent recreational drug present in smoke and smokeless tobacco products. "	( In vitro nicotine induced superoxide mediated DNA fragmentation in lymphocytes: protective role of Andrographis paniculata Nees. Das, S; Gautam, N; Neogy, S; Roy, S, 2009)	2.21
"Nicotine is a nonspecific agonist of nicotinic acetylcholine receptors. "	( Role of nicotinic acetylcholine receptor subtypes on nicotine-induced neurogenic contractile response alternation in the rabbit gastric fundus. Bozkurt, NB; Ercan, ZS; Ozturk Fincan, GS; Sarioglu, Y; Vural, IM, 2009)	2.05
"Nicotine is a major component of tobacco, and has been reported to inhibit proliferation and differentiation of osteoblasts."	( Nicotine suppresses bone sialoprotein gene expression. Araki, S; Han, J; Li, X; Mezawa, M; Nakayama, Y; Ogata, Y; Sasaki, Y; Takai, H; Wang, S, 2009)	2.52
"Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS). "	( Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome. Bravo, E; Cerpa, V; Coddou, C; Eugenín, J; Llona, I; Otárola, M; Reyes-Parada, M; von Bernhardi, R, 2008)	2.08
"Nicotine is a major alkaloid accumulating in the vacuole of tobacco (Nicotiana tabacum), but the transporters involved in the vacuolar sequestration are not known. "	( Multidrug and toxic compound extrusion-type transporters implicated in vacuolar sequestration of nicotine in tobacco roots. Goto, Y; Hashimoto, T; Inai, K; Matsuoka, K; Sato, Y; Shitan, N; Shoji, T; Takase, H; Toyooka, K; Yazaki, K; Yazaki, Y, 2009)	2.01
"Hair nicotine is a known biomarker for monitoring long-term environmental tobacco smoke (ETS) exposure and smoking status. "	( Determination of hair nicotine by gas chromatography-mass spectrometry. Awang, R; Harn, GL; Ismail, S; Lajis, R; Man, CN, 2009)	1.18
"Nicotine dependence is a major health problem, with a large amount of smoking-related premature deaths and disabilities. "	( Pharmacogenetics of smoking cessation therapy. Bau, CH; Bizarro, L; Dobler, CJ; Kortmann, GL, 2010)	1.8
"Nicotine serves as a primary reinforcer but also potently enhances responding for nonnicotine stimuli with reinforcing properties. "	( Bupropion and nicotine enhance responding for nondrug reinforcers via dissociable pharmacological mechanisms in rats. Caggiula, AR; Donny, EC; Levin, ME; Mays, KL; Palmatier, MI; Sved, AF, 2009)	2.16
"Nicotine acts as an agonist of nicotinic acetylcholine receptors, which belong to a superfamily of neurotransmitter-gated ion channels. "	( Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: the role of nicotinic acetylcholine receptor subtypes. Ercan, ZS; Ozturk Fincan, GS; Sarioglu, Y; Vural, IM, 2010)	2.11
"Nicotine is a major component of cigarette smoking which may be involved in the progress of atherogenesis. "	( Nicotine induces cyclooxygenase-2 and prostaglandin E(2) expression in human umbilical vein endothelial cells. Qiao, ZD; Tang, MP; Wang, LY; Wang, ZX; Xu, WJ; Yao, CJ; Zhou, Y, 2010)	3.25
"Nicotine dependence is a disease of constantly growing importance. "	( Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives. Filip, M; Przegaliński, E; Zaniewska, M, )	3.02
"(S)-Nicotine is a psychostimulant legal drug responsible for causing addiction to tobacco smoking. "	( A critical evaluation of a nicotine vaccine within a self-administration behavioral model. Azar, MR; Dickerson, TJ; Janda, KD; Koob, GF; Moreno, AY; Warren, NA, 2010)	1.22
"Nicotine addiction is a chronic disorder characterized by a relatively high rate of relapse even after long period of abstinence. "	( Effects of varenicline and mecamylamine on the acquisition, expression, and reinstatement of nicotine-conditioned place preference by drug priming in rats. Biala, G; Budzynska, B; Staniak, N, 2010)	2.02
"Nicotine is a naturally occurring plant alkaloid."	( Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor. Greene, CM; McElvaney, NG; O'Neill, SJ; Ramsay, H; Wells, RJ, 2010)	1.08
"Nicotine is a molecule that crosses the hematoencephalic barrier and acts in several areas of central nervous system including the NTS, where it may interact with some neurotransmitter systems and contributes to the development of hypertension in subjects with genetic predisposition to this disease."	( Adenosine receptor type 2a is differently modulated by nicotine in dorsal brainstem cells of Wistar Kyoto and spontaneously hypertensive rats. de Ferrari, MF; de Matsumoto, JP; Fior-Chadi, DR, 2010)	1.33
"Nicotine reportedly is a risk factor for periodontitis, but accurate data regarding nicotine-induced alveolar bone loss is lacking. "	( Micro-computerized tomography analysis of alveolar bone loss in ligature- and nicotine-induced experimental periodontitis in rats. Liu, YF; Wang, J; Wang, XJ; Wen, LY; Wu, LA, 2010)	2.03
"Nicotine is a major alkaloid of tobacco, which can increase free radical formation, leading to osteoporosis. "	( Effects of nicotine administration and nicotine cessation on bone histomorphometry and bone biomarkers in Sprague-Dawley male rats. Hapidin, H; Mohamed, N; Othman, F; Shuid, AN; Soelaiman, IN, 2011)	2.2
"Nicotine is a widely used drug of abuse exerting number of effects on the central nervous system. "	( Nicotine effects on rat seizures susceptibility and hippocampal neuronal degeneration. Maresova, D; Pokorny, J; Riljak, V, 2010)	3.25
"Nicotine (NIC) is a highly addictive substance that interacts with different subtypes of nicotinic acetylcholine receptors widely distributed in the central and peripheral nervous systems. "	( Fluctuations in central and peripheral temperatures induced by intravenous nicotine: central and peripheral contributions. Kiyatkin, EA; Tang, JS, 2011)	2.04
"Nicotine is a major component of cigarette smoke, and it stimulates the α7 nicotinic acetylcholine receptors."	( Nicotine-induced differential modulation of autoimmune arthritis in the Lewis rat involves changes in interleukin-17 and anti-cyclic citrullinated peptide antibodies. Moudgil, KD; Rajaiah, R; Yang, YH; Yu, H, 2011)	2.53
"Hair nicotine is a better predictor of reductions in BW for GA than either hair cotinine or self-report. "	( Hair biomarkers as measures of maternal tobacco smoke exposure and predictors of fetal growth. Almeida, ND; Koren, G; Kramer, MS; Platt, RW, 2011)	0.88
"Nicotine dependence is a significant addiction with many health consequences. "	( Nicotine dependence: health consequences, smoking cessation therapies, and pharmacotherapy. Grief, SN, 2011)	3.25
"Nicotine is considered to be a specific substrate for UGT2B10, an isoform of human uridine diphosphate glucuronosyltransferase (UGT). "	( Liquid chromatography-tandem mass spectrometry method for measurement of nicotine N-glucuronide: a marker for human UGT2B10 inhibition. Grimm, SW; Guo, J; Zhou, D, 2011)	2.04
"Nicotine functions as a negative feature in a Pavlovian discriminated goal-tracking task. "	( Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor. Bevins, RA; Li, C; Murray, JE; Penrod, RD; Walker, AW; Wells, NR, 2011)	3.25
"Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine."	( Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase. An, B; Hao, D; Lu, Y; Wang, S; Xu, Y; Yang, S; Yin, Y, 2011)	1.11
"Nicotine is a risk factor for various diseases, including osteoporosis, oral cancer, and periodontal disease. "	( Effects of nicotine on proliferation and osteoblast differentiation in human alveolar bone marrow-derived mesenchymal stem cells. Kim, BS; Kim, HJ; Kim, SJ; Lee, J; Lee, SJ; Park, YJ; You, HK, 2012)	2.21
"Nicotine is a psychoactive drug whose intensity of the addiction is so tremendous that it is now the fastest growing public health hazard in the world. "	( Consequences of nicotine exposure during different phases of rat brain development. Khanna Sood, P; Nehru, B; Sharma, S, 2012)	2.17
"Nicotine in nectar acts as a partial repellent, which may keep pollinators moving between plants and enhance cross-pollination."	( Honeybees and nectar nicotine: deterrence and reduced survival versus potential health benefits. Köhler, A; Nicolson, SW; Pirk, CW, 2012)	1.42
"Nicotine vaccines are a new class of immunotherapeutics under development."	( Nicotine vaccines. Fahim, RE; Fuller, SA; Kalnik, MW; Kessler, PD, 2011)	2.53
"Nicotine is a natural alkaloid produced by tobacco plants, and the mechanisms of its catabolism by microorganisms are diverse. "	( Functional identification of two novel genes from Pseudomonas sp. strain HZN6 involved in the catabolism of nicotine. Chen, L; Liu, W; Ma, Y; Qiu, J; Wen, Y; Wu, L, 2012)	2.03
"Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases. "	( Protective effect of vitamin E and epicatechin against nicotine-induced oxidative stress in rats. Al-Malki, AL; Moselhy, SS, 2013)	2.08
"Nicotine is a pharmacological factor during tobacco smoking that releases bilateral striatal DA, but more in the left brain."	( Denicotinized versus average nicotine tobacco cigarette smoking differentially releases striatal dopamine. Domino, EF; Domino, JS; Evans, C; Guthrie, S; Koeppe, RA; Ni, L; Wang, H; Yang, W; Zubieta, JK, 2013)	1.4
"Nicotine is a major psychoactive ingredient in tobacco yet very few individuals quit smoking with the aid of nicotine replacement therapy. "	( Preclinical evidence that activation of mesolimbic alpha 6 subunit containing nicotinic acetylcholine receptors supports nicotine addiction phenotype. Brunzell, DH, 2012)	2.03
"Nicotine is an important chemical compound in nature that has been regarded as an environmental toxicant causing various preventable diseases. "	( Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation. Ren, Y; Tang, H; Wang, L; Wu, G; Xu, P; Yao, Y; Yu, H, 2012)	2.05
"Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise."	( Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation. Broaddus, WC; Chung, TD; Jameson, MJ; Khalil, AA; Lin, PS, 2013)	2.55
"Nicotine is a key harmful component of tobacco and cigarettes, and the development of low-nicotine cigarettes is of increasing importance in the market. "	( Nicotine degradation enhancement by Pseudomonas stutzeri ZCJ during aging process of tobacco leaves. Gao, Y; Li, X; Shi, Y; Shu, M; Wang, C; Zhao, L; Zhong, W; Zhu, C, 2012)	3.26
"Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking."	( Nicotine vaccines to treat tobacco dependence. Delijewski, M; Goniewicz, ML, 2013)	2.55
"Nicotine is a heavily used addictive drug acquired through smoking tobacco. "	( Nicotine delivery to rats via lung alveolar region-targeted aerosol technology produces blood pharmacokinetics resembling human smoking. Feldman, JL; Liang, J; Shao, XM; Xie, XS; Xu, B; Zhu, Y, 2013)	3.28
"Nicotine tolerance is a well-established behavioral phenomenon in rodents, yet the underlying mechanism remains elusive."	( Low-dose adolescent nicotine and methylphenidate have additive effects on adult behavior and neurochemistry. Bachus, SE; Fryxell, KJ; McDonald, CG; Smith, LN; Smith, RF; Wheeler, TL, 2013)	1.43
"Nicotine is a potent inhibitor of the immune response and is protective against experimental autoimmune encephalomyelitis (EAE). "	( Differential modulation of EAE by α9*- and β2*-nicotinic acetylcholine receptors. Gan, Y; Kousari, A; Lukas, RJ; Morley, BJ; Patel, V; Shi, FD; Simard, AR; St-Pierre, S; Whiteaker, P, 2013)	1.83
"Nicotine addiction is a chronic relapsing condition that can be difficult to treat. "	( Clinical efficacy of bupropion in the management of smoking cessation. Jorenby, D, 2002)	1.76
"Nicotine is a potent stimulus for the hypothalamic-pituitary-adrenal (HPA) axis. "	( Effect of adrenergic antagonists and cyclooxygenase inhibitors on the nicotine-induced hypothalamic-pituitary-adrenocortical activity. Bugajski, AJ; Bugajski, J; Gadek-Michalska, A; Głód, R, 2002)	1.99
"Nicotine addiction is a major public health issue. "	( Nicotine withdrawal syndrome: behavioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala. Hanoune, J; Monory, K; Nomikos, GG; Tzavara, ET, 2002)	3.2
"Nicotine addiction is a chronic disease characterized by frequent relapse. "	( [Behavioral and cognitive therapy to break the smoking habit. Review of the literature]. Aubin, HJ; Lagrue, G; Le Foll, B, 2002)	1.76
"Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the age at which smoking typically commences. "	( Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase. Cousins, MM; Seidler, FJ; Slikker, W; Slotkin, TA; Xu, Z, 2002)	2.15
"Nornicotine (NORNIC) is a tobacco alkaloid and behaviorally active nicotine metabolite in vivo. "	( Locomotor stimulant effects of nornicotine: role of dopamine. Bardo, MT; Brown, RW; Dwoskin, LP; Green, TA; Phillips, SB, 2002)	1.22
"Nicotine is a powerful stimulant of the sympathoadrenal system, causing the release of peripheral catecholamines and activation of catecholamine biosynthesis. "	( Chronic nicotine treatment leads to sustained stimulation of tyrosine hydroxylase gene transcription rate in rat adrenal medulla. Sterling, CR; Sun, B; Tank, AW, 2003)	2.2
"Nicotine is a likely contributor to these adverse effects, with fetal brain as one target organ."	( Maternal vaccination against nicotine reduces nicotine distribution to fetal brain in rats. Calvin, AD; Keyler, DE; LeSage, MG; Pentel, PR; Shoeman, D, 2003)	1.33
"Nicotine is a major pharmacologically active component of cigarette smoke. "	( Inhibitory effect of Sejin-Eum I/II on nicotine- and cigarette extract-induced cytotoxicity in human lung fibroblast. An, NH; Jin, JS; Jung, KP; Kim, HM; Kim, MS; Lee, JH; Lee, JK; Moon, SJ; Yi, JM, 2003)	2.03
"Nornicotine is a major nicotine metabolite in the CNS and has been shown to participate in the aberrant glycation of proteins in vivo in a process termed nornicotine-based glycation."	( Glycation of the amyloid beta-protein by a nicotine metabolite: a fortuitous chemical dynamic between smoking and Alzheimer's disease. Dickerson, TJ; Janda, KD, 2003)	1.1
"Nicotine is a very potent and efficacious desensitizing agent at this neuronal nicotinic receptor."	( Nicotine is highly effective at producing desensitization of rat alpha4beta2 neuronal nicotinic receptors. Paradiso, KG; Steinbach, JH, 2003)	2.48
"Nicotine intake is a necessary but insufficient factor in maintaining tobacco smoking behavior, and nonpharmacological factors associated with smoking play a key role. "	( Placebo effects of tobacco smoking and other nicotine intake. Caggiula, A; Conklin, C; Perkins, K; Sayette, M, 2003)	2.02
"Nicotine is an alkaloid that is used by large numbers of people. "	( Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors. Grant, A; Liu, L; Oxford, G; Simon, SA; Yang, T; Zhang, ZS; Zhu, W, 2004)	3.21
"Nicotine is a neuroteratogen that targets cell development and synaptic function into adolescence, when smoking typically commences. "	( Sex-selective hippocampal alterations after adolescent nicotine administration: effects on neurospecific proteins. Garcia, SJ; Seidler, FJ; Slikker, W; Slotkin, TA; Tate, CA; Xu, Z, 2003)	2.01
"Nicotine is an important component in cigarette smoke that can activate the growth-promoting pathways to facilitate the development of lung cancer. "	( Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis. Deng, X; Flagg, T; Gao, F; Jin, Z, 2004)	3.21
"Nicotine is a naturally occurring alkaloid found in many plants. "	( Nicotine, its metabolism and an overview of its biological effects. Yildiz, D, 2004)	3.21
"Nicotine proved not to be an efficient insecticide, although it may facilitate removal of adult lice because it induces muscle twitches that may affect the insect's normal grip on hair follicles."	( Use of topical nicotine for treatment of Pediculus humanus capitis (Anaplura: Pediculidae). Burkhart, CG; Burkhart, CN, 2000)	1.38
"Nicotine is a dibasic amine with a pK(a) of 8.0. "	( Short-term distribution of nicotine in the rat lung. Brewer, BG; Roberts, AM; Rowell, PP, 2004)	2.06
"Nicotine is a colorless and volatile liquid alkaloid naturally occurring in the leaves and stems of Nicotiana tabacum and Nicotiana rustica. "	( Metabolism and biochemical effects of nicotine for primary care providers. Gregersen, PK; Malhotra, AK; Metz, CN, 2004)	2.04
"Nicotine is a popular addictive drug used among the adolescent population, and it has long been questioned whether nicotine use in adolescence may lead to the use of other psychostimulant drugs. "	( Nicotine treatment produces persistent increases in amphetamine-stimulated locomotor activity in periadolescent male but not female or adult male rats. Collins, SL; Izenwasser, S; Montano, R, 2004)	3.21
"Nicotine is a major immunosupressive component in cigarette smoke."	( [Effects of cigarette smoke constituents on the immune system with special consideration of patients with tuberculosis]. Nagorni-Obradović, L, 2004)	1.04
"Nicotine is a teratogen in rats and possibly in humans. "	( Reduced nicotine distribution from mother to fetal brain in rats vaccinated against nicotine: time course and influence of nicotine dosing regimen. Bramwell, TJ; Calvin, AD; Dufek, MB; Keyler, DE; Le, CT; LeSage, MG; Pentel, PR; Raphael, DE; Ross, CA, 2005)	2.21
"Nornicotine is an N-demethylated metabolite of nicotine. "	( CYP2A6 AND CYP2B6 are involved in nornicotine formation from nicotine in humans: interindividual differences in these contributions. Aoki, Y; Fukami, T; Katoh, M; Nakajima, M; Nakamura, A; Sakai, H; Takamiya, M; Yamanaka, H; Yokoi, T, 2005)	1.22
"The nicotine metabolism is an important determinant of the clearance of nicotine."	( Interindividual variability in nicotine metabolism: C-oxidation and glucuronidation. Nakajima, M; Yokoi, T, 2005)	1.1
"Nornicotine is a secondary tobacco alkaloid that is produced by the N-demethylation of nicotine. "	( Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase. Bowen, SW; Dewey, RE; Gavilano, L; Siminszky, B, 2005)	1.31
"Nicotine is a major component of tobacco smoke contributing to the initiation and persistence of the harmful tobacco habit in human smokers. "	( Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity. Kenny, PJ; Markou, A, 2006)	3.22
"Nicotine acts as a typical drug of abuse in experimental animals and humans."	( Nicotine as a typical drug of abuse in experimental animals and humans. Goldberg, SR; Le Foll, B, 2006)	3.22
"Oral nicotine is a safe potential treatment of inflammatory bowel disease, but there is considerable variation in tolerance."	( Preliminary observations of oral nicotine therapy for inflammatory bowel disease: an open-label phase I-II study of tolerance. Evans, BK; Ingram, JR; Rhodes, J; Thomas, GA, 2005)	1.12
"Nicotine is a strong activator of the hypothalamus pituitary adrenal (HPA) axis. "	( The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers. Kirschbaum, C; Rohleder, N, 2006)	1.78
"Nicotine is a major component in cigarette smoke that activates the growth-promoting pathways to facilitate the development of lung cancer. "	( Protein kinase Ciota promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of micro- and m-calpains. Deng, X; Xu, L, 2006)	2.07
"Nicotine is an alkaloid obtained from the leaves of the tobacco plant, and it is the main constituent of tobacco smoke. "	( Facts about nicotine toxicity. Karaconji, IB, 2005)	2.15
"Nicotine is a very widely used drug of abuse, which has many neurovegetative behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptor. "	( Nicotine an efficient tool of the neurobiological research today, the tool of treatment tomorrow? Langmeier, M; Riljak, V, 2005)	3.21
"Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer."	( Nicotine prevents the apoptosis induced by menadione in human lung cancer cells. Cheng, H; Lu, H; Shang, X; Tian, Y; Wang, S; Zhang, T; Zheng, C; Zhou, R, 2006)	2.5
"Nicotine is a very widely used drug of abuse, which exerts a number of neurovegetative behavioural effects by interacting with the neuronal nicotinic acetylcholine receptor. "	( Changes in the number of nitrergic neurons in rats hippocampus following nicotine administration. Jandová, K; Langmeier, M; Maresová, M; Milotová, M; Pokorný, J; Riljak, V; Trojan, S, 2006)	2.01
"Nicotine is a major component of cigarette smoke and has been found to play an important role in angiogenesis. "	( Effects of nicotine on angiogenesis and restenosis in a rabbit model. Jiaquan, L; Qi, B; Ruixing, Y; Tangwei, L, 2007)	2.17
"Nicotine is a major addictive compound in cigarette. "	( Simple, rapid and sensitive assay method for simultaneous quantification of urinary nicotine and cotinine using gas chromatography-mass spectrometry. Awang, R; Gam, LH; Ismail, S; Lajis, R; Man, CN, 2006)	2
"Nicotine dependence is a chronic mental illness that is characterized by a negative affective state upon tobacco smoking cessation and relapse after periods of abstinence. "	( Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Bruijnzeel, AW; Gold, MS; Wilson, C; Zislis, G, 2007)	2
"Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. "	( Permanent, sex-selective effects of prenatal or adolescent nicotine exposure, separately or sequentially, in rat brain regions: indices of cholinergic and serotonergic synaptic function, cell signaling, and neural cell number and size at 6 months of age. MacKillop, EA; Rudder, CL; Ryde, IT; Seidler, FJ; Slotkin, TA; Tate, CA, 2007)	2.03
"Nornicotine is an undesirable secondary alkaloid in cultivated tobacco, because it serves as a precursor to N'-nitrosonornicotine (NNN), a tobacco-specific nitrosamine with suspected carcinogenic properties. "	( Genetic engineering of Nicotiana tabacum for reduced nornicotine content. Bowman, ML; Burnley, LE; Bush, L; Coleman, NP; Gavilano, LB; Hayes, A; Kalengamaliro, NE; Siminszky, B, 2006)	1.2
"Nicotine is a better probe according to its specificity, while coumarin is still valuable to be used for a routine CYP2A6 phenotyping since the test employs a non-invasive method."	( In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais. Fujieda, M; Kamataki, T; Kiyotani, K; Peamkrasatam, S; Sriwatanakul, K; Yamazaki, H; Yoovathaworn, K, 2006)	1.33
"Nicotine is a major alkaloid in cigarette smoke."	( Nicotine promotes cell proliferation via alpha7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells. Cho, CH; Lam, EK; Tai, EK; Wong, HP; Wu, WK; Yu, L, 2007)	2.5
"Nicotine is an irritant molecule in the cigarette that contributes airway hyper-reactivity. "	( Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized guinea-pig trachea. Bagcivan, I; Cevit, O; Durmus, N; Kaya, T; Parlak, A; Sarac, B, 2007)	2.06
"Hair nicotine is a valid measure of SHS exposure. "	( Measuring tobacco smoke exposure among smoking and nonsmoking bar and restaurant workers. Hahn, EJ; Hall, LA; Okoli, CT; Rayens, MK, 2007)	0.85
"Nicotine is an active substance present in tobacco."	( Effect of hesperidin on matrix metalloproteinases and antioxidant status during nicotine-induced toxicity. Balakrishnan, A; Menon, VP, 2007)	1.29
"Nicotine is a developmental neurotoxicant but the proposed "sensitization-homeostasis" model postulates that even in adulthood nicotine permanently reprograms synaptic function. "	( Separate or sequential exposure to nicotine prenatally and in adulthood: persistent effects on acetylcholine systems in rat brain regions. Ryde, IT; Seidler, FJ; Slotkin, TA, 2007)	2.06
"Nornicotine is an undesirable alkaloid in tobacco, because it serves as a precursor for N'-nitrosonornicotine, a potent carcinogen in laboratory animals."	( Isolation and characterization of the cytochrome P450 gene CYP82E5v2 that mediates nicotine to nornicotine conversion in the green leaves of tobacco. Gavilano, LB; Siminszky, B, 2007)	1.08
"1. Nicotine is a well studied pleiotropic agent which occurs naturally in tobacco smoke and has been largely accused for many of the adverse effects of smoking on the cardiovascular system, including autonomic imbalance, endothelial dysfunction and coronary blood flow dysregulation. "	( New insights into the sympathetic, endothelial and coronary effects of nicotine. Adamopoulos, D; Argacha, JF; van de Borne, P, 2008)	1.2
"Nicotine acts as an agonist of nicotinic acetylcholine receptors. "	( Hydrogen peroxide and antioxidizing enzymes involved in modulation of transient facilitatory effects of nicotine on neurogenic contractile responses in rat gastric fundus. Dileköz, E; Ercan, ZS; Ozger Ilhan, S; Oztürk, GS; Sarioglu, Y; Vural, IM, 2008)	2
"Nicotine is an anti-inflammatory, but the association between smoking and asthma is highly contentious and some report that smoking cessation increases the risk of asthma in ex-smokers."	( Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. Campen, M; Hutt, J; Kim, KC; Koga, T; Langley, RJ; Mishra, NC; Peña-Philippides, JC; Razani-Boroujerdi, S; Rir-Sima-Ah, J; Singh, SP; Sopori, ML; Tesfaigzi, Y, 2008)	2.51
"The nicotine gum seems to be a relatively simple, cost-effective, and practical tool for physicians to enhance and reinforce their antismoking advice."	( Effects of nicotine chewing gum and follow-up appointments in physician-based smoking cessation. Fagerström, KO, 1984)	1.14
"Nicotine appears to be a contributing factor in maintaining cigarette smoking, but experimental evidence for its reinforcing effects is scarce. "	( Maintenance and suppression of behavior by intravenous nicotine injections in squirrel monkeys. Goldberg, SR; Spealman, RD, 1982)	1.95
"Thus nicotine chewing-gum is a useful aid to giving up smoking and is probably acceptable even for people with cardiovascular disease."	( Comparison of nicotine chewing-gum and psychological treatments for dependent smokers. Feyerabend, C; Jarvis, MJ; Raw, M; Russell, MA, 1980)	1.08
"Nicotine is a naturally occurring alkaloid found primarily in members of the solanaceous plant family, which includes tobacco. "	( The genotoxic potential of nicotine and its major metabolites. Caldwell, WS; de Bethizy, JD; Doolittle, DJ; Hayes, AW; Lee, CK; Winegar, R, 1995)	2.03
"Nicotine gum is an effective adjunct to minimal-contact smoking cessation materials plus monetary incentive in a population-based sample of smokers."	( Nicotine gum and self-help behavioral treatment for smoking relapse prevention: results from a trial using population-based recruitment. Fortmann, SP; Killen, JD, 1995)	2.46
"The nicotine patch appears to be an important aid to smokers who want to quit, primarily when used as an adjuvant to other forms of assistance."	( Nicotine patch use in the general population: results from the 1993 California Tobacco Survey. Farkas, AJ; Gilpin, E; Pierce, JP, 1995)	2.29
"Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. "	( Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells. Chowdhury, P; Doi, R; Imamura, M; Inoue, K; Nishikawa, M; Rayford, PL; Takaori, K, 1995)	1.98
"Nicotine gum is an important adjunct for smoking cessation for many smokers, and long-term use of nicotine gum will occur in a small percentage of patients. "	( Cessation of long-term nicotine gum use--a prospective, randomized trial. Enright, PL; Fagerström, KO; Hurt, RD; Lauger, GG; Marusić, Z; Offord, KP; Scanlon, PD, 1995)	2.04
"The nicotine gum is a flexible dosing form that allows for self-titration of nicotine. "	( Nicotine chewing gum and nicotine patch. Fagerström, KO; Tönnesen, P, 1995)	2.29
"The nicotine patch is an effective aid to quitting smoking across different patch-use strategies. "	( The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. Baker, TB; Fiore, MC; Jorenby, DE; Smith, SS, )	0.99
"Nicotine (Nic) is a potent stimulus for ACTH secretion, and this response appears to be mediated by central catecholamine secretion. "	( Selective administration of nicotine into catecholaminergic regions of rat brainstem stimulates adrenocorticotropin secretion. Foster, CA; Matta, SG; Sharp, BM, 1993)	2.02
"Nicotine is a potent substance to counteract neuroleptic-induced parkinsonism."	( [Neuroleptics and nicotine]. Erdmann, R, 1995)	1.35
"Nicotine replacement is an effective smoking cessation aid and should form the basis for treating moderate to heavy smokers."	( Strategies for smoking cessation. Foulds, J, 1996)	1.02
"Nicotine is a new in vivo probe for phenotyping of CYP2A6 in humans."	( Role of human cytochrome P4502A6 in C-oxidation of nicotine. Funae, Y; Inoue, K; Kamataki, T; Kuroiwa, Y; Nagashima, K; Nakajima, M; Nunoya, K; Shimada, N; Yamamoto, T; Yokoi, T, 1996)	1.27
"Nicotine is a potent chemical that has powerful effects on the human body, especially when administered rapidly or at high doses."	( The direct effects of nicotine use on human health. Fiore, MC; Remington, PL; Van Gilder, TJ, 1997)	1.33
"Nicotine is a potent stimulus for the secretion of ACTH, and norepinephrinergic neurons originating in the brainstem are involved. "	( Adrenocorticotropin response and nicotine-induced norepinephrine secretion in the rat paraventricular nucleus are mediated through brainstem receptors. Fu, Y; Matta, SG; Sharp, BM; Valentine, JD, 1997)	2.02
"Hair nicotine seems to be a good quantitative measure of exposure to tobacco smoke during the previous months both among active and passive smokers."	( Hair nicotine concentrations in mothers and children in relation to parental smoking. Hagen, JA; Jaakkola, JJ; Magnus, P; Nafstad, P; Zahlsen, K, )	1.1
"Nicotine is a major constituent of tobacco and exerts a number of physiological effects. "	( [Metabolism of nicotine--mechanism and clinical effects of toxicity]. Kwiatkowska, D; Szajerka, G, 1997)	2.09
"Nicotine is a natural alkaloid that has considerable stimulatory effects on the central nervous system (CNS)."	( Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism. Corsini, GU; Fornai, F; Maggio, R; Racagni, G; Riva, M; Vaglini, F, 1997)	1.26
"The nicotine skin patch is a popular and effective means of smoking cessation. "	( Use of the nicotine skin patch by smokers in 20 communities in the United States, 1992-1993. Cummings, KM; Hyland, A; Hymowitz, N; Manley, M; Ockene, JK, 1997)	1.24
"Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. "	( Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro. Villablanca, AC, 1998)	3.19
"Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. "	( Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Bandettini, PA; Bloom, AS; Cho, JK; Fuller, SA; Harsch, HH; Hawkins, M; Hoffmann, RG; Pankiewicz, J; Rao, SM; Stein, EA, 1998)	3.19
"Nicotine is an addictive drug and arguably this should be known better in the health industry than in any other industry."	( Smoking habits and cessation programme in an Australian teaching hospital. Crocker, H; Jones, TE; Ruffin, RE, 1998)	1.02
"Nicotine serves as a reinforcer and induces a robust discriminative stimulus which is primarily mediated by neuronal nicotinic receptors. "	( The role of monoamine neurotransmitter systems in the nicotine discriminative stimulus. Freedland, CS; Mansbach, RS; Rovetti, CC, 1998)	1.99
"Nicotine is a natural alkaloid that has considerable stimulatory effects on the CNS."	( Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. Armogida, M; Corsini, GU; Fornai, F; Maggio, R; Molteni, R; Racagni, G; Riva, M; Vaglini, F, 1998)	2.46
"Nicotine lozenges are a potential aid to smoking cessation but their safety, efficacy and abuse potential remain to be properly evaluated."	( Nicotine absorption and dependence in unlicensed lozenges available over the counter. Feyerabend, C; Foulds, J; Jarvis, MJ; Russell, MA, 1998)	3.19
"Nicotine is an ingredient of all tobacco products and pharmacologically the most active component of tobacco smoke."	( Nicotine-enhanced epithelial differentiation in reconstructed human oral mucosa in vitro. Cho, KH; Chung, JH; Eun, HE; Kim, KH; Kwon, OS; Park, KC; Suh, DH, )	2.3
"Nicotine is a diprotic base with pKa's of 3.12 (pyridine ring) and 8.02 (pyrrolidine ring)."	( Optimization study for the reversed-phase ion-pair liquid chromatographic determination of nicotine in commercial tobacco products. Ciolino, LA; McCauley, HA; Smallwood, AW; Turner, JA; Yi, TY, 1999)	1.25
"Nicotine is a tobacco alkaloid known to be important in the acquisition and maintenance of tobacco smoking. "	( Nornicotine is self-administered intravenously by rats. Bardo, MT; Crooks, PA; Dwoskin, LP; Green, TA, 1999)	2.37
"Nicotine is an alkaloid that has been reported to disrupt the rate of OM, reduce ovulation and fertilization rates, and increase diploidy."	( Sensitivity of mouse oocytes to nicotine-induced perturbations during oocyte meiotic maturation and aneuploidy in vivo and in vitro. Caldito, G; London, SN; Mailhes, JB; Young, D, 2000)	1.31
"Nicotine is a potent regulator of bFGF and TGF-beta 1 production and release by aortic SMC, and it seems to play an important role in the development and progression of atherosclerosis and neointimal fibrous hyperplasia."	( Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1. Borrelli, V; Cavallaro, A; Corvino, V; Cucina, A; Mariani, V; Randone, B; Santoro D'Angelo, L; Sapienza, P, 2000)	3.19
"Nicotine is a consistent component of smoked and smokeless tobacco; the presence of 0.2% nicotine significantly increased the permeability of oral mucosa to NNN and 2% nicotine caused a further increase."	( Penetration of N-nitrosonornicotine (NNN) across oral mucosa in the presence of ethanol and nicotine. Du, X; Kremer, MJ; Squier, CA; Wertz, PW, 2000)	1.33
"Nicotine has proven to be a useful prototypic compound for the family of nicotinic compounds."	( Development of nicotinic drug therapy for cognitive disorders. Levin, ED; Rezvani, AH, 2000)	1.03
"Nicotine is a cholinergic agonist that acts, not only post-synaptically, but also releases pre-synaptic acetylcholine, and in animal models has been shown to reverse spatial memory decline in rats with lesion in the medial septal nucleus and to show recovery on memory in aged monkeys. "	( Nicotine for Alzheimer's disease. López-Arrieta, JM; Rodríguez, JL; Sanz, F, 2000)	3.19
"Nicotine is a well-known toxic alkaloid substance with several teratogenic effects. "	( Teratogenic effects of nicotine on rat skin. Deveci, E; Eralp, A; Inalöz, HS; Inalöz, SS, 2000)	2.06
"Nicotine is an additive drug and the most effective methods for treating dependence are nicotine replacement therapy (NRT) and bupropion SR."	( Pharmacologic treatments for the nicotine dependent smoker. Glover, ED; Glover, PN, )	1.86
"Nicotine is a cholinergic agonist that also has a presynaptic effect in releasing acetylcholine. "	( Efficacy and safety of nicotine on Alzheimer's disease patients. López-Arrieta, JM; Rodríguez, JL; Sanz, F, 2001)	2.06
"Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the time that smoking typically commences. "	( Fetal and adolescent nicotine administration: effects on CNS serotonergic systems. Ali, SF; Seidler, FJ; Slikker, W; Slotkin, TA; Xu, Z, 2001)	2.07
"Nornicotine is a tobacco alkaloid and an active nicotine metabolite, which accumulates in brain to pharmacologically relevant concentrations following repeated nicotine administration to rats. "	( Contributory role for nornicotine in nicotine neuropharmacology: nornicotine-evoked [3H]dopamine overflow from rat nucleus accumbens slices. Bardo, MT; Crooks, PA; Dwoskin, LP; Green, TA, 2001)	1.24
"Nicotine addiction is an extremely complex process that involves biological, psychological, behavioral, and cultural factors. "	( Behavioral and cognitive effects of smoking: relationship to nicotine addiction. Heishman, SJ, 1999)	1.99
"The nicotine vapor inhaler is a new pharmacological adjunct shown to be effective in placebo-controlled trials."	( New medications for nicotine dependence treatment. Hurt, RD, 1999)	1.11
"Nicotine is a psychoactive drug presenting a diverse array of biological activities, some positive, such as enhancement of cognitive performances, others negative, such as addiction liability. "	( Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine. Abagyan, R; Schapira, M; Totrov, M, 2002)	1.98
"Nicotine acts as an addictive substance by binding to acetylcholine receptors and causing the release of dopamine in the brain, though other signalling substances are also important for the action of nicotine in the central nervous system."	( [Nicotine dependence--medico-biological aspects]. Dybing, E; Sanner, T, 2002)	1.95
"Nicotine is a suspected fetal neuroteratogen."	( Accelerated metabolism of nicotine and cotinine in pregnant smokers. Benowitz, NL; Dempsey, D; Jacob, P, 2002)	1.34
"Nicotine addiction is a complex behavioral phenomenon comprising effects on several neural systems. "	( Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics. Corrigall, WA; Picciotto, MR, 2002)	2.01
"The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence smokers."	( Efficacy of a nicotine lozenge for smoking cessation. Dresler, CM; Gilburt, SJ; Hajek, P; Shiffman, S; Strahs, KR; Targett, DA, 2002)	1.23
"Nicotine patches are an effective aid to tobacco dependence treatment. "	( Tobacco dependence and the nicotine patch. Clinical guidelines for effective use. Baker, TB; Fiore, MC; Jorenby, DE; Kenford, SL, 1992)	2.02
"Nicotine is a vasoconstrictor that reduces nutritional blood flow to the skin, resulting in tissue ischemia and impaired healing of injured tissue."	( Smoking and wound healing. Silverstein, P, 1992)	1
"Nicotine is a paradoxical drug in that it both stimulates and depresses functions. "	( Nicotine as a psychoactive drug. Murray, JB, 1991)	3.17
"Nicotine replacement is a useful adjunct in treating tobacco dependence."	( Nicotine dependence: a preventable risk factor for other diseases. Cohen, C; Henningfield, JE, )	2.3
"Nicotine poisoning is a rarely reported toxicosis. "	( Nicotine poisoning in a dog. Vig, MM, 1990)	3.16
"Nicotine was shown to be a weak inhibitor of [3H]dopamine accumulation, with an IC50 of approximately 0.2-0.4 mM."	( The effect of nicotine on catecholaminergic storage vesicles. Kramer, HK; Lajtha, A; Reith, ME; Sershen, H, 1989)	1.36
"Nicotine is a psychoactive drug with effects that reinforce tobacco use despite known adverse health consequences. "	( Nicotine dependence. Milhorn, HT, 1989)	3.16
"Nicotine is an addictive drug and tobacco smoking an addictive habit."	( [Toxicologic and pharmacologic methods in the control of smoking behavior]. Ackermann, E, 1989)	1
"Nicotine is a potent secretagogue for the release of adrenocorticotropin (ACTH) from the anterior pituitary in vivo. "	( Nicotine elevates rat plasma ACTH by a central mechanism. Beyer, HS; Matta, SG; McAllen, KM; Sharp, BM, 1987)	3.16
"Nicotine replacement is a promising new approach to aid smoking cessation, and various methods of delivery are being developed. "	( Nicotine replacement in smoking cessation. Absorption of nicotine vapor from smoke-free cigarettes. Feyerabend, C; Jarvis, MJ; Russell, MA; Sutherland, G, 1987)	3.16
"Nicotine is an unusual compound because it shows both odorant and pharmacological properties."	( Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant. Dodd, GH; Edwards, DA; Mather, RA; Shirley, SG, 1987)	1.24
"Nicotine is a toxic substance which is readily available from a wide variety of sources. "	( Suicide plan by nicotine poisoning: a review of nicotine toxicity. Saxena, K; Scheman, A, 1985)	2.06

Effects

Nicotine has a differential effect on extinction of fear conditioning depending on when it is administered. Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists.

Nicotine has wellknown, unpleasant side effects, e.g., transient dizziness, nausea, and nicotine-induced nystagmus (NIN). Nicotine chewing gum has been available since 1982. It was shown to increase smoking cessation rates by approximately 1.5- to 2-fold after 12 months.

Excerpt	Reference	Relevance
"Nicotine has a unique profile among drugs of abuse. "	( The incentive amplifying effects of nicotine: Roles in alcohol seeking and consumption. King, CP; Meyer, PJ, 2022)	2.44
"Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence."	( Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers. Benowitz, NL; Dempsey, DA; Jacob, P; Liakoni, E; St Helen, G; Tyndale, RF, 2019)	1.5
"Nicotine stress has an allelopathic inhibitory effect on seeds and a hormesis effect on germinated seeds and seedlings, which has an enhancement effect (<50 mg kg"	( Potential risks of nicotine on the germination, growth, and nutritional properties of broad bean. Bai, YX; Chen, Y; Cheng, YD; Jia, M; Wang, D; Wang, G; Wu, T; Yang, HW, 2021)	1.67
"Nicotine has a moderate effect on dopaminergic neuron survival that becomes more evident as flies age."	( Nicotine suppresses Parkinson's disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Campusano, JM; Carvajal-Oliveros, A; Domínguez-Baleón, C; Narváez-Padilla, V; Reynaud, E; Zárate, RV, 2021)	2.79
"Nicotine has a profound influence on the carotenoid metabolism in halophilic Archaea of the class Halobacteria. "	( Effects of nicotine on the biosynthesis of carotenoids in halophilic Archaea (class Halobacteria): an HPLC and Raman spectroscopy study. Hirschberg, J; Jehlička, J; Mann, V; Oren, A, 2018)	2.31
"Nicotine has a broad impact on both the central and peripheral nervous systems. "	( Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach. Fan, R; Li, X; Liu, M; Liu, X; Wang, J; Zhang, L, 2015)	2.15
"Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear."	( Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine. Kasraeian, M; Khademi, F; Miladpour, B; Mostafavi-Pour, Z; Totonchi, H; Zal, F, 2016)	1.35
"Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. "	( Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily. Carroll, FI; Cunningham, CS; Javors, MA; McMahon, LR; Moerke, MJ, 2016)	2.27
"Nicotine has a wide range of effects. "	( Nicotine in a small-to-moderate dose does not cause a significant increase in plasma catecholamine levels in newborn piglets. Andresen, JH; Godang, K; Munkeby, BH; Saugstad, OD; Stray-Pedersen, B, 2008)	3.23
"Nicotine has an adverse influence on blood vessel functionality, repair and maintenance."	( Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption. Cooper, RG; Magwere, T, )	1.12
"Nicotine has a detrimental effect on cutaneous flap survival; although there are no experimental studies proving this effect on musculocutaneous flaps."	( Nicotine on rat TRAM flap. Campos, JH; Ely, PB; Ferreira, LM; Gomes, HC; Juliano, Y; Kobayashi, LA, )	2.3
"Nicotine has an antinociceptive effect in animal models. "	( A transdermal nicotine patch is not effective for postoperative pain management in smokers: a pilot dose-ranging study. Cheng, S; Conell-Price, JS; Flood, P; Hong, D; Olson, LC, 2009)	2.16
"Nicotine has a differential effect on extinction of fear conditioning depending on when it is administered."	( Nicotine and extinction of fear conditioning. Elias, GA; Gould, TJ; Gulick, D; Wilkinson, DS, 2010)	2.52
"Nicotine has a protective effect on the dopaminergic neurons in the MPTP-treated mice."	( [The protective effect of nicotine on dopaminergic neuron of Parkinson's disease mice]. Feng, YH; Li, Y; Peng, Y; Sun, YP; Yu, DQ; Zhang, DM; Zhang, WQ; Zhao, J, 2007)	2.08
"Nicotine has a synergistic effect of arecoline-induced MGMT expression."	( The expression of O(6) -methylguanine-DNA methyltransferase in human oral keratinocytes stimulated with arecoline. Chang, YC; Ho, YC; Hsu, HI; Lee, SS; Tsai, CH; Yu, CC, 2013)	1.11
"Nicotine has a powerful preventive effect on neuroleptic-induced dopamine D2 receptor upregulation in the rat. "	( Does nicotine affect D2 receptor upregulation? A case-control study. Negrete, JC; Seeman, MV; Seeman, P; Shammi, CM; Silvestri, S, 2004)	2.28
"Nicotine has an overall detrimental effect on NP disc cells cultured in vitro. "	( Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Akmal, M; Anand, B; Goodship, A; Kesani, A; Singh, A; Wiseman, M, 2004)	2.17
"Nicotine also has a neuroprotective action."	( Smoking, nicotine and Parkinson's disease. Quik, M, 2004)	1.46
"Nicotine has a long and storied history in physiology and pharmacology. "	( Nicotine psychopharmacology research contributions to United States and global tobacco regulation: a look back and a look forward. Henningfield, JE; Zeller, M, 2006)	3.22
"Nicotine has a therapeutic benefit in treating Alzheimer's disease (AD). "	( Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model. Chen, Q; Liu, Q; Qin, C; Zhang, J; Zhao, B; Zhu, H, 2007)	2.06
"Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status."	( Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis. Bülow, J; Gottrup, F; Hemmingsen, U; Jørgensen, S; Loft, S; Petersen, LJ; Sørensen, LT, 2009)	2.14
"Nicotine dependence has a biological substratum defined as "neuroadaptation to nicotine." 2."	( Nicotine-related brain disorders: the neurobiological basis of nicotine dependence. Ochoa, EL, 1994)	2.45
"Nicotine has a biphasic effect on sleep: at low concentrations, it leads to relaxation and sedation and at high concentrations inhibits sleep."	( [Prevention and treatment of sleep disorders through regulation] of sleeping habits]. Bailly, D; Onen, F; Onen, SH; Parquet, P, 1994)	1.01
"Nicotine has a similar effect on the coronary circulation."	( Recent problems with paracervical vasopressin: a possible synergistic reaction with nicotine. Groudine, SB; Morley, JN, 1996)	1.24
"Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs."	( Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Levin, ED; McEvoy, J; Rose, JE; Wilson, W, 1996)	2.46
"Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function."	( In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Feyerabend, C; Madretsma, S; Tak, CJ; van Dijk, JP; Wilson, JH; Wolters, LM; Zijlstra, FJ, 1996)	2.07
"Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated."	( Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis. Cohen, P; Eliakim, R; Fich, A; Karmeli, F; Rachmilewitz, D, 1998)	2.08
"Nicotine has a wide range of biological effects, and proteases have been extensively studied for their biological roles in living creatures. "	( Protease activity induced by nicotine in human cells. Chi, XJ; Hasegawa, R; Kita, K; Nakajima, N; Suzuki, N; Takahashi, S; Tanzawa, H; Wang, XL; Yamamori, H; Yokoe, H, 1999)	2.04
"Nicotine has a multitude of biological actions in the central and peripheral nervous systems where nicotinic acetylcholine receptors are found. "	( Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines. Friedman, H; Hakki, A; Hallquist, N; Pross, S; Wecker, L, 2000)	2.06
"Nicotine has a small molecular weight and is absorbed via the mucosa (Guccal or nasal), the pulmonary alveoli and the skin. "	( [Pharmacology of nicotine]. Bourlaud, I; Patte, F; Perault, MC; Underner, M, 1992)	2.07
"Thus nicotine has a detrimental effect on the development of newborn offspring in general and incisor development in particular."	( Postnatal effects of nicotine on incisor development of albino mouse. Saad, AY, 1990)	1.05
"Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement."	( Self-administration by female rats of low doses of nicotine alone vs. nicotine in tobacco smoke extract. Abass, G; Hawkey, A; Holloway, Z; Levin, ED; Pace, C; Rezvani, AH; Rose, JE; Wells, C, 2021)	2.32
"Nicotine has been widely studied for its pro-dopaminergic effects. "	( The role of the SLC6A3 3' UTR VNTR in nicotine effects on cognitive, affective, and motor function. Chan, RCK; Ettinger, U; Faßbender, K; Lui, SSY; Plieger, T; Poulsen, J; Reuter, M; Schröder, R, 2022)	2.44
"Nicotine has a unique profile among drugs of abuse. "	( The incentive amplifying effects of nicotine: Roles in alcohol seeking and consumption. King, CP; Meyer, PJ, 2022)	2.44
"Nicotine has undeniable detrimental effects on patients undergoing plastic surgeries like cutaneous necrosis, skin flap failure and surgical site infection. "	( Pathophysiology of nicotine, place of nicotine substitutes and electronic cigarettes in plastic surgery: A review of the literature. Atlan, M; Cristofari, S; Guérif, V, 2022)	2.49
"Nicotine has been reported to be an addictive drug and the leading cause of tobacco addiction worldwide with consequent renal implications."	( Changes in Serum Electrolytes, Urea and Creatinine in Nicotiana tabacum-treated Rats. Ante, I; Inwang, U; Nwaji, AR; Nwoke, FA, 2022)	1.44
"Nicotine has been used during pregnancy and lactation as a tobacco harm reduction strategy. "	( Nicotine exposure through breastfeeding affects brain-derived neurotrophic factor and synaptic proteins levels in the brain of stressed adult female mice. Almeida, CAF; Antunes-Rodrigues, J; Ceron, CS; de Amorim, GES; Dias, MVS; Elias, LLK; Garcia, RCT; Marcourakis, T; Pereira Júnior, AA; Ribeiro, JM; Ruginsk, SG; Silva, AO; Torres, LH, 2022)	3.61
"Nicotine has been shown to facilitate hippocampal-dependent context fear conditioning (FC), but not hippocampal-independent delay cued fear conditioning. "	( The effect of acute nicotine administration on human delay cued and context fear conditioning. Astur, RS; Gould, TJ; Palmisano, AN, 2023)	2.68
"Nicotine has both rewarding and aversive effects. "	( Dips in dopamine say "no" to nicotine. Nicola, SM; Servonnet, A, 2022)	2.46
"Nicotine has been shown to attenuate the phagocytic ability of macrophage; however, the underlying mechanism remains unclear."	( Nicotine Suppresses Phagocytic Ability of Macrophages by Regulating the miR-296-3p-SIRP Chen, Z; Huang, X; Liu, Z; Luo, X; Wang, F; Wang, Y; Zhao, G; Zhao, Y, 2023)	3.07
"Nicotine has shown the toxic effects on male reproductive system, and testicular damage is associated with ferroptosis, which is a non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. "	( The role of ferroptosis mediated by Bmal1/Nrf2 in nicotine -induce injury of BTB integrity. Cheng, J; Hua, R; Jiang, Z; Li, Q; Li, X; Xu, D; Yang, L; Zhang, Z, 2023)	2.61
"Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research."	( The co-use of nicotine and prescription psychostimulants: A review of their behavioral and neuropharmacological interactions. Bevins, RA; McNealy, KR; Weyrich, L, 2023)	1.99
"Nicotine has been found to reduce pain, but whether it is involved in the regulation of nerve regeneration and the underlying mechanism are unknown."	( Nicotine Decreases Nerve Regeneration and Pain Behaviors via PTEN and Downstream Inflammation-Related Pathway in Two Rat Nerve Injury Models. Chen, S; Fang, Y; Li, L; Liao, Y; Tang, J; Wang, L; Zhang, T, 2023)	3.07
"Hand nicotine levels have been proposed to measure THS pollution in the environment of children, but little is known about its variability and stability over time and correlates of change."	( Changes and stability of hand nicotine levels in children of smokers: Associations with urinary biomarkers, reported child tobacco smoke exposure, and home smoking bans. Dodder, NG; Hoh, E; Lopez Galvez, N; Mahabee-Gittens, EM; Matt, GE; Merianos, AL; Quintana, PJE; Stone, L; Wullenweber, C, 2023)	1.65
"Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence."	( Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers. Benowitz, NL; Dempsey, DA; Jacob, P; Liakoni, E; St Helen, G; Tyndale, RF, 2019)	1.5
"Nicotine in tobacco has negative effects on tissues, kidneys, and eyes especially, where microcirculation is vitally important for the survival and functioning."	( Nicotine increased VEGF and MMP2 levels in the rat eye and kidney. Ates, M; Guvendi, G; Hosgorler, F; Kandis, S; Kanit, L; Karakilic, A; Koc, B; Unsal, SK; Uysal, N; Yuksel, O, 2019)	2.68
"Nicotine has been linked to the development of abdominal aortic aneurysms. "	( Isoflavone Ameliorated Oxidative Stress and Vascular Damages in Nicotine-Administrated Mice. Hoshino, K; Kugo, H; Moriyama, T; Nakamura, T; Sasoh, T; Sukketsiri, W; Zaima, N, 2019)	2.2
"Nicotine has dichotomous, age-dependent effects on microglial morphology and immune transcript profiles."	( Microglial activation increases cocaine self-administration following adolescent nicotine exposure. Cano, M; Gad, M; Green, KN; Leslie, FM; Linker, KE; Tawadrous, P; Wood, MA, 2020)	1.51
"Nicotine has been shown to improve cognitive deficits induced by inflammation and other stimuli."	( Acute Nicotine Treatment Alleviates LPS-Induced Impairment of Fear Memory Reconsolidation Through AMPK Activation and CRTC1 Upregulation in Hippocampus. Jin, X; Shen, X; Shu, H; Song, M; Sun, Y; Wang, M; Zhang, J, 2020)	1.76
"Nicotine use disorder has been associated with glutamatergic alterations within the basal ganglia that might contribute to relapse. "	( Direct administration of ifenprodil and citalopram into the nucleus accumbens inhibits cue-induced nicotine seeking and associated glutamatergic plasticity. Foster Olive, M; Gipson, CD; Leyrer-Jackson, JM; McCallum, J; Piña, JA, 2020)	2.22
"Nicotine has recently been shown to enhance the motivational value of non-nicotine stimuli in nonhumans. "	( Nicotine Facilitation of Conditioned Place Preference to Food Reward in Humans. Astur, RS; Palmisano, AN, 2020)	3.44
"Nicotine has also been detected in wild mushrooms, so there are other causes of contamination as well as pesticide."	( Validation and measurement uncertainty of GC-MS quantification method for nicotine in dried mushrooms using QuEChERS extraction. Kang, HH; Kim, YJ; Lee, JG; Moon, JY; Yun, CI, 2020)	1.51
"Nicotine has been commonly used in pyschopharmacological studies, showing its benefits as a pharmacological stimulant on cognitive performance. "	( Effects of nicotine on pupil size and performance during multiple-object tracking in non-nicotine users. Boehler, CN; Laeng, B; Mathôt, S; Wardhani, IK, 2020)	2.39
"Nicotine stress has an allelopathic inhibitory effect on seeds and a hormesis effect on germinated seeds and seedlings, which has an enhancement effect (<50 mg kg"	( Potential risks of nicotine on the germination, growth, and nutritional properties of broad bean. Bai, YX; Chen, Y; Cheng, YD; Jia, M; Wang, D; Wang, G; Wu, T; Yang, HW, 2021)	1.67
"Nicotine exposure has been reported to modify bone cell function and the osseous metabolism with potential effects on the rate of orthodontic tooth movement."	( Effect of nicotine exposure on the rate of orthodontic tooth movement: A meta-analysis based on animal studies. Athanasiou, AE; Jyothish, S; Kaklamanos, EG; Makrygiannakis, MA, 2021)	2.47
"Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories."	( Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers. Gilbert, DG; Lindt, JD; Pergadia, ML; Pizzagalli, DA; Rabinovich, NE; Whitton, AE, 2021)	1.57
"Nicotine has been shown to decrease appetite, food intake (FI) and body weight, but the mechanisms are unclear. "	( Nicotine and energy balance: A review examining the effect of nicotine on hormonal appetite regulation and energy expenditure. Bellissimo, N; Schwartz, A, 2021)	3.51
"Nicotine has a moderate effect on dopaminergic neuron survival that becomes more evident as flies age."	( Nicotine suppresses Parkinson's disease like phenotypes induced by Synphilin-1 overexpression in Drosophila melanogaster by increasing tyrosine hydroxylase and dopamine levels. Campusano, JM; Carvajal-Oliveros, A; Domínguez-Baleón, C; Narváez-Padilla, V; Reynaud, E; Zárate, RV, 2021)	2.79
"Nicotine has been known to enhance recognition memory in various species. "	( Nicotine Enhances Object Recognition Memory via Stimulating α4β2 and α7 Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex of Mice. Deyama, S; Esaki, H; Fukao, A; Ito, S; Izumi, S; Kaneda, K; Nishitani, N, 2021)	3.51
"Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS)."	( Protective effects of quercetin on nicotine induced oxidative stress in 'HepG2 cells'. Bolouki, A; Yarahmadi, A; Zal, F, 2017)	1.45
"Nicotine has been reported to enhance OST performance in rats and the present study assessed whether this effect generalizes to human performance."	( Validation of the human odor span task: effects of nicotine. Drobes, DJ; MacQueen, DA, 2017)	1.43
"Nicotine has been shown to enhance the reinforcement and reward-responsiveness of non-nicotine stimuli. "	( The effects of nicotine on conditioning, extinction, and reinstatement in humans. Astur, RS; de Wit, H; Hudd, EC; McQuade, CM; Palmisano, AN, 2018)	2.28
"Nicotine has adverse cellular and molecular effects on oral mucosa, bone, and teeth. "	( Efficacy of vitamins E and C for reversing the cytotoxic effects of nicotine and cotinine. Jamshidi, M; Mansuri Torshizi, A; Rezaei Esfahrood, Z; Sotoudeh, S; Torshabi, M, 2017)	2.13
"Nicotine has long been considered a potent therapeutic agent for neuroprotection. "	( Nicotine-Induced Neuroprotection against Cognitive Dysfunction after Partial Hepatectomy Involves Activation of BDNF/TrkB Signaling Pathway and Inhibition of NF-κB Signaling Pathway in Aged Rats. Ji, F; Li, D; Li, J; Liu, H; Tang, W; Wan, T; Wei, P; Zheng, Q; Zhou, H; Zhou, J, 2018)	3.37
"Nicotine has a profound influence on the carotenoid metabolism in halophilic Archaea of the class Halobacteria. "	( Effects of nicotine on the biosynthesis of carotenoids in halophilic Archaea (class Halobacteria): an HPLC and Raman spectroscopy study. Hirschberg, J; Jehlička, J; Mann, V; Oren, A, 2018)	2.31
"Nicotine has been recognized to trigger various neuronal disabilities in the fetal brain and long-lasting behavioral deficits in offspring. "	( Human brain organoid-on-a-chip to model prenatal nicotine exposure. Qin, J; Wang, L; Wang, Y; Zhu, Y, 2018)	2.18
"Nicotine from NRT has some reinforcement enhancing effects in humans, possibly in a manner consistent with nicotine via e-cigarettes but not tobacco smoking. "	( Reinforcement Enhancing Effects of Nicotine Via Patch and Nasal Spray. Boldry, MC; Karelitz, JL; Perkins, KA, 2019)	2.23
"Nicotine has negative effects on tissue repair, little research concerns its effect on the cartilage repair of tissue engineering stem cells. "	( Histone hypo-acetylation of Sox9 mediates nicotine-induced weak cartilage repair by suppressing BMSC chondrogenic differentiation. Chen, L; Deng, Y; Tie, K; Wang, H; Wen, Y; Wu, M, 2018)	2.19
"Nicotine has previously been shown to have therapeutic effects on attentional and cognitive abnormalities in psychosis."	( Nicotine and varenicline ameliorate changes in reward-based choice strategy and altered decision-making in methamphetamine-treated rats. Fukumoto, K; Kusaba, M; Mizoguchi, H; Wang, T; Yamada, K, 2019)	2.68
"Nicotine has reward-enhancing properties and may increase the value of alcohol."	( The effect of nicotine and nicotine+monoamine oxidase inhibitor on the value of alcohol. DeHart, WB; Frye, CCJ; Galizio, A; Haynes, JM; Odum, AL, 2019)	1.6
"Nicotine has also historically been used as a de-wormer but was removed from the market when modern anthelmintics became available."	( Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes. Charvet, CL; Cortet, J; Courtot, E; Guégnard, F; Neveu, C, 2018)	2.64
"Nicotine has acute pain-relieving properties, and tobacco smokers often report using cigarettes to cope with pain. "	( Menthol cigarette use and pain reporting among African American adults seeking treatment for smoking cessation. Buckner, JD; Ditre, JW; Hughes, MT; Kosiba, JD; LaRowe, LR; Norton, PJ; Smits, JAJ; Zvolensky, MJ, 2019)	1.96
"Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS) in some parts of female reproductive system, but the effect of nicotine on endometrium that plays an important role in reproductive biology stays unexplored."	( Nicotine-Induced Oxidative Stress in Human Primary Endometrial Cells. Khademi, F; Mohammadi, N; Totonchi, H; Zal, F; Zare, R, )	2.3
"Nicotine has been widely used as a template for the synthesis of ligands that prefer α4β2 nAChRs subtypes."	( Minimal Structural Changes Determine Full and Partial Nicotinic Receptor Agonist Activity for Nicotine Analogues. Bermúdez, I; Gonzalez-Gutierrez, JP; Guerra-Díaz, N; Hernández-Morantes, JJ; Hodar, M; Iturriaga-Vásquez, P; Paillali, P; Pérez-Sánchez, H; Pessoa-Mahana, H; Reyes-Parada, M; Viscarra, F, 2019)	1.45
"Nicotine has dose-dependent manner on serum osteocalcin and serum DPD level. "	( Effects of nicotine on markers of bone turnover in ovariectomized rats. Amelia, Y; Ernanda, SA; Jonatan, A; Juwono, MA; Kartikaningtyas, AN; Maulidya, E; Parhusip, YM; Sananta, P, 2019)	2.35
"Nicotine has also been studied for its antidyskinetic effect on levodopa-induced dyskinesia."	( Effect of nicotine on the pharmacokinetics of levodopa. Iwaki, H; Kaneta, M; Kubo, M; Kyaw, WT; Nagai, M; Nishikawa, N; Nomoto, M; Tsujii, T, )	1.26
"Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems."	( Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats. Afroze, S; Dostal, DE; Frenzel, A; Glaser, SS; Guerrier, M; Jensen, K; Meng, F; Nizamutdinov, D; Rahal, K; Sterling, M; Ueno, Y, 2013)	1.55
"Nicotine patch therapy has not been shown to be efficacious for increasing long-term (≥6 months) tobacco abstinence rates among smokeless tobacco (ST) users. "	( A randomized phase II clinical trial of high-dose nicotine patch therapy for smokeless tobacco users. Croghan, IT; Ebbert, JO; Hurt, RD; Schroeder, DR, 2013)	2.09
"Nicotine has been shown to speed attentional reorienting in cued target detection tasks, and work in young adults suggest that individuals carrying the apolipoprotein E (APOE) e4 allele might show greater sensitivity to the cognitive effects of nicotine. "	( Nicotine effects on attentional reorienting in mid-age adults, and interactions with apolipoprotein E status. Dowell, NG; Evans, S; Gray, M; King, SL; Rusted, JM; Tabet, N; Tofts, PS, 2013)	3.28
"Nicotine patches have been reliably demonstrated to improve smoking cessation outcomes but most users still lapse, and then relapse, during treatment. "	( Effect of high-dose nicotine patch on craving and negative affect leading up to lapse episodes. Ferguson, SG; Shiffman, S, 2014)	2.17
"Nicotine medications have been useful for smoking cessation but have not found widespread popularity among smokers, perhaps because of slow nicotine delivery and other sensory characteristics that differ from cigarettes."	( Emerging nicotine delivery products. Implications for public health. Benowitz, NL, 2014)	1.54
"Nicotine has been shown to improve symptoms associated with ADHD, including problems with attention, working memory and response inhibition."	( Nicotine-stimulated release of [3H]norepinephrine is reduced in the hippocampus of an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat. Howells, FM; Russell, VA; Sterley, TL, 2014)	2.57
"Nicotine has been shown to enhance the motivational properties of non-nicotine stimuli. "	( Nicotine enhances the expression of a sucrose or cocaine conditioned place preference in adult male rats. Buffalari, DM; Donny, EC; Levin, ME; Marfo, NY; Smith, TT; Sved, AF; Thiels, E; Weaver, MT, 2014)	3.29
"Nicotine has a broad impact on both the central and peripheral nervous systems. "	( Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach. Fan, R; Li, X; Liu, M; Liu, X; Wang, J; Zhang, L, 2015)	2.15
"Nicotine has already been reported to promote VSMC migration from the tunica media to atheromatous plaques in the vascular intima. "	( Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type. Chen, Z; Izumi, T; Kohama, K; Nagai, T; Nakamura, A; Nasu-Kawaharada, R; Ohshima, N; Okagaki, T; Yoshiyama, S, 2014)	3.29
"Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. "	( Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery. Fujiwara, H; Hagimori, K; Hashikawa-Hobara, N; Kawasaki, H; Ono, N; Takatori, S; Takayama, F; Tangsucharit, P; Yokomizo, A, 2015)	3.3
"Nicotine has been shown to affect cortical excitability measured using transcranial magnetic stimulation in smoking and non-smoking subjects in different ways. "	( Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine. Ambrus, GG; Amu, R; Batsikadze, G; Grundey, J; Nitsche, MA; Paulus, W, 2015)	2.07
"Nicotine has been shown to attenuate experimental autoimmune encephalomyelitis (EAE) through inhibiting inflammation in microglial populations during the disease course. "	( Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis. Gao, Z; Legakis, L; Nissen, JC; Tsirka, SE, 2015)	3.3
"Nicotine has been reported to prolong the wound healing; however, we showed that the topical application of 10(-4) M nicotine promoted murine wound healing. "	( Exploration of the wound healing effect of topical administration of nicotine in combination with collagen scaffold in a rabbit model. Masuoka, H; Morimoto, N; Ogino, S; Sakamoto, M; Suzuki, S, 2016)	2.11
"Nicotine has practical applications relating to smoking cessation devices and alternative nicotine products. "	( Genetic Factors for Enhancement of Nicotine Levels in Cultivated Tobacco. Chen, H; Gao, Y; Lewis, RS; Li, W; Qu, R; Shi, J; Song, Z; Wang, B, 2015)	2.14
"Nicotine has been explored as an adjunctive medication for management of postoperative pain.  "	( Intranasal or transdermal nicotine for the treatment of postoperative pain. Chou, R; Dana, T; Fu, R; Matthews, AM, 2016)	1.46
"Nicotine has been determined in exhaled breath and oral fluids of both, active and passive smokers."	( Passive exposure to nicotine from e-cigarettes. Armenta, S; de la Guardia, M; Elbal, L; Gallart-Mateu, D, 2016)	1.48
"Nicotine use has been reported to ameliorate symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). "	( Adult attention-deficit/hyperactivity disorder and nicotine withdrawal: a qualitative study of patient perceptions. Biechl, AC; Buadze, A; Eich, D; Fisher, CE; Frei, A; Hiestand, N; Huber, A; Liebrenz, M; Nellen, R, 2016)	2.13
"Nicotine has well-documented effects on the growth and colonization of Streptococcus mutans. "	( Effect of nicotine on cariogenic virulence of Streptococcus mutans. Gregory, RL; Huang, R; Li, M; Qiu, W; Xu, X; Zhou, X, 2016)	2.28
"Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear."	( Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine. Kasraeian, M; Khademi, F; Miladpour, B; Mostafavi-Pour, Z; Totonchi, H; Zal, F, 2016)	1.35
"Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. "	( Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily. Carroll, FI; Cunningham, CS; Javors, MA; McMahon, LR; Moerke, MJ, 2016)	2.27
"Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. "	( Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion. Barrett, ST; Bevins, RA; Geary, TN; Steiner, AN, 2017)	2.12
"Nicotine has been proposed to be a primary reinforcer and a reinforcement enhancer. "	( Effects of contingent and noncontingent nicotine on lever pressing for liquids and consumption in water-deprived rats. Dar, R; Frenk, H; Martin, J; Shalev, U; Vitouchanskaia, C, 2017)	2.17
"Nicotine has strong addictive as well as procognitive properties. "	( Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Bueno-Junior, LS; Moghaddam, B; Simon, NW; Wegener, MA, 2017)	2.31
"Nicotine has been associated with vasoconstriction and an impaired cellular healing response. "	( A systematic review and meta-analysis of pre-clinical studies assessing the effect of nicotine on osseointegration. Abduljabbar, T; Akram, Z; Ghanem, A; Javed, F; Kellesarian, SV; Vohra, F, 2017)	2.12
"Nicotine treatment has long been associated with alterations in alpha4beta2(*) nicotinic acetylcholine receptor (nAChR) expression that modify dopaminergic function. "	( Long-term nicotine treatment differentially regulates striatal alpha6alpha4beta2* and alpha6(nonalpha4)beta2* nAChR expression and function. Bordia, T; Grady, SR; McIntosh, JM; Perez, XA; Quik, M, 2008)	2.19
"Nicotine has been recognized for years as being pharmacologically responsible for the sympathoexcitatory effects of smoking. "	( Nicotine does not compromise resting myocardial blood flow autoregulation in smokers at high cardiovascular risk. Argacha, JF; Garcia, C; Goldman, S; Gujic, M; Preumont, N; van de Borne, P; Van Simaeys, G; Xhaët, O, 2008)	3.23
"Nicotine, which has anxiolytic effects in rodents and humans was found to diminish this novel tank diving response in zebrafish."	( The role of alpha7 and alpha4beta2 nicotinic receptors in the nicotine-induced anxiolytic effect in zebrafish. Bencan, Z; Levin, ED, 2008)	1.31
"Nicotine has been shown to be antinociceptive in the postoperative period in animal studies. "	( Transdermal nicotine patch for postoperative pain management: a pilot dose-ranging study. Cheng, S; Conell-Price, J; Flood, P; Hong, D, 2008)	2.17
"Nicotine nasal spray has been 1 of the most successful forms of nicotine-replacement therapy in adult populations. "	( A randomized trial of nicotine nasal spray in adolescent smokers. Auerback, GM; Benowitz, NL; Moscicki, AB; Rubinstein, ML, 2008)	2.1
"Nicotine has a wide range of effects. "	( Nicotine in a small-to-moderate dose does not cause a significant increase in plasma catecholamine levels in newborn piglets. Andresen, JH; Godang, K; Munkeby, BH; Saugstad, OD; Stray-Pedersen, B, 2008)	3.23
"Nicotine has been found to enhance learning in a variety of tasks, including contextual fear conditioning. "	( Nicotine enhances context learning but not context-shock associative learning. Gould, TJ; Kenney, JW, 2008)	3.23
"Nicotine has an adverse influence on blood vessel functionality, repair and maintenance."	( Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption. Cooper, RG; Magwere, T, )	1.12
"Nicotine has effects on various cognitive processes, though most studies in humans have focused on the amelioration of cognitive deficits experienced during drug withdrawal."	( Nicotine self-medication of cognitive-attentional processing. Drobes, DJ; Evans, DE, 2009)	2.52
"Nicotine has been proposed to be neuroprotective through anti-amyloid beta (Abeta) effects, anti-excitotoxic effects, and anti-free radical effects."	( Absence of effect of chronic nicotine administration on amyloid beta peptide levels in transgenic mice overexpressing mutated human APP (Sw, Ind). Anand, K; Lue, LF; Reid, RT; Sabbagh, MN; Stadnick, T; Walker, DG, 2008)	1.36
"Nicotine has been shown to induce endothelial dysfunction, which is an early marker of atherosclerosis. "	( Effect of nicotine and nicotine metabolites on angiotensin-converting enzyme in human endothelial cells. Ljungberg, LU; Persson, K, )	1.98
"Nicotine exposure has been associated with weight loss and reduced weight gain. "	( Smokeless nicotine exposure has no lasting effect on fasting or postglucose circulation leptin in young rats. Fakiri, Z; Swislocki, AL, 2008)	2.19
"Nicotine has also been suggested to benefit functional recovery in rodent models of stroke."	( Nicotine does not improve recovery from learned nonuse nor enhance constraint-induced therapy after motor cortex stroke in the rat. Alaverdashvili, M; Lim, DH; Whishaw, IQ, 2009)	2.52
"Nicotine has been shown to reduce both tone and muscular activity in the human colon by releasing nitric oxide (NO) from nerves. "	( Nicotine-induced neurogenic relaxation in the mouse colon: changes with dextran sodium sulfate-induced colitis. Fujino, H; Hamada, Y; Horie, S; Murakami, I; Murayama, T; Yamane, S, 2009)	3.24
"Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals."	( Anxiolytic effects of nicotine in a rodent test of approach-avoidance conflict. Ben-Shahar, OM; Cohen, A; Ettenberg, A; Groysman, M; Noorbehesht, K; Velazquez, MA; Young, RW, 2009)	2.11
"Nicotine has been proposed to alleviate negative symptoms."	( Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Conway, JL, 2009)	1.48
"Nicotine has been found in many studies to improve cognitive function. "	( Nicotinic antagonist effects in the mediodorsal thalamic nucleus: regional heterogeneity of nicotinic receptor involvement in cognitive function. Brotherton, J; Cannady, R; Gotschlich, E; Kolia, N; Lau, E; Levin, ED; Wee, B; Weir, R, 2009)	1.8
"Nicotine has a detrimental effect on cutaneous flap survival; although there are no experimental studies proving this effect on musculocutaneous flaps."	( Nicotine on rat TRAM flap. Campos, JH; Ely, PB; Ferreira, LM; Gomes, HC; Juliano, Y; Kobayashi, LA, )	2.3
"Nicotine has been shown to increase responding maintained by turning off a houselight. "	( Responding maintained by primary reinforcing visual stimuli is increased by nicotine administration in rats. Dallery, J; Raiff, BR, 2009)	2.03
"Nicotine has been intensively studied by the tobacco industry, for instance for its addictive effect at the lowest possible rates."	( [Chemicals added to cigarettes and their effects on tobacco dependence]. Cornuz, J; Gonseth, S, 2009)	1.07
"Nicotine has deleterious effects on some vital visceral organs with observations similar to those reported in women smokers."	( Effect of nicotine administration on weight and histology of some vital visceral organs in female albino rats. Bolarinwa, AF; Iranloye, BO, 2009)	1.48
"Nicotine has an antinociceptive effect in animal models. "	( A transdermal nicotine patch is not effective for postoperative pain management in smokers: a pilot dose-ranging study. Cheng, S; Conell-Price, JS; Flood, P; Hong, D; Olson, LC, 2009)	2.16
"Nicotine has a differential effect on extinction of fear conditioning depending on when it is administered."	( Nicotine and extinction of fear conditioning. Elias, GA; Gould, TJ; Gulick, D; Wilkinson, DS, 2010)	2.52
"Nicotine has been reported to increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) in sublingual acini due to neurotransmitter release from nerve terminals associated with the cell preparation (1). "	( Ca2+ mobilization by nicotine through synaptic activation in rat parotid acini. Hosokawa, R; Iida, T; Inagaki, T; Inenaga, K; Ono, K, 2009)	2.11
"Nicotine has been well established as an impulsive action-inducing agent, but it remains unknown whether endogenous acetylcholine affects impulsive action via nicotinic acetylcholine receptors. "	( Endogenous acetylcholine modulates impulsive action via alpha4beta2 nicotinic acetylcholine receptors in rats. Izumi, T; Ohmura, Y; Tsutsui-Kimura, I; Yamaguchi, T; Yoshida, T; Yoshioka, M, 2010)	1.8
"Nicotine has high affinity for beta(2)*-nAChRs (nAChRs containing the beta(2)* subunit, for which * represents other subunits that may also be part of the receptor) and displaces specifically bound (123)I-5-IA."	( Quantification of smoking-induced occupancy of beta2-nicotinic acetylcholine receptors: estimation of nondisplaceable binding. Batis, JC; Bois, F; Carson, RE; Cosgrove, KP; Esterlis, I; Perkins, E; Seibyl, JP; Staley, JK; Stiklus, SM, 2010)	1.08
"Nicotine treatment has known to produce an inverse relationship between body weight and food intake in rodents. "	( High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice. Choi, SH; Chun, BG; Hong, GH; Hur, YN; Shin, KH, 2010)	2.04
"Nicotine has been definitively shown to be critically involved in the neural bases of tobacco addiction. "	( Histamine H(1) antagonist treatment with pyrilamine reduces nicotine self-administration in rats. Cauley, M; Cousins, V; Hampton, D; Levin, ED; Petro, A; Pruitt, M; Rose, J; Slade, S; Wells, C, 2011)	2.05
"Nicotine has been demonstrated to enhance the subsequent use of illicit drugs in animals and humans. "	( The sensitizing effect of acute nicotine on amphetamine-stimulated behavior and dopamine efflux requires activation of β2 subunit-containing nicotinic acetylcholine receptors and glutamate N-methyl-D-aspartate receptors. Gnegy, ME; Jutkiewicz, EM; Kim, MN; Zhang, M, 2011)	2.1
"Nicotine has a protective effect on the dopaminergic neurons in the MPTP-treated mice."	( [The protective effect of nicotine on dopaminergic neuron of Parkinson's disease mice]. Feng, YH; Li, Y; Peng, Y; Sun, YP; Yu, DQ; Zhang, DM; Zhang, WQ; Zhao, J, 2007)	2.08
"Hair nicotine and cotinine have been proposed as longer-term markers of exposure to secondhand smoke. "	( Time course of nicotine and cotinine incorporation into samples of nonsmokers' beard hair following a single dose of nicotine polacrilex. Alexander, JR; Bernert, JT; McGuffey, JE; Sosnoff, CS, 2011)	1.24
"Nicotine has been found to produce dose-dependent increases in impulsive choice (preference for smaller, sooner reinforcers relative to larger, later reinforcers) in rats. "	( Nicotine and the behavioral mechanisms of intertemporal choice. Dallery, J; Locey, ML, 2011)	3.25
"Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain."	( Varenicline, a partial agonist at neuronal nicotinic acetylcholine receptors, reduces nicotine-induced increases in 20% ethanol operant self-administration in Sprague-Dawley rats. Bartlett, SE; Bito-Onon, JJ; Chatterjee, S; Holgate, J; Simms, JA, 2011)	1.05
"Nicotine has anti- and pro-inflammatory properties in various cells. "	( Nicotine induces pro-inflammatory response in aortic vascular smooth muscle cells through a NFκB/osteopontin amplification loop-dependent pathway. Wang, Y; Xue, S; Yang, W; Zhang, F, 2012)	3.26
"Nicotine withdrawal has also been associated with an activation of 5-HT neurotransmission, although withdrawal increases anxiety."	( Shifting topographic activation and 5-HT1A receptor-mediated inhibition of dorsal raphe serotonin neurons produced by nicotine exposure and withdrawal. Commons, KG; Sperling, R, 2011)	1.3
"Nicotine has been shown to improve both memory and attention when assessed through speeded motor responses. "	( Prompt but inefficient: nicotine differentially modulates discrete components of attention. Bundesen, C; Coull, JT; Vangkilde, S, 2011)	2.12
"Nicotine has been shown to decrease Aβ neurotoxicity via inhibition of caspase-dependent apoptosis, but it is unknown if its neuroprotection is mediated through caspase-independent pathways."	( α7 Nicotinic receptor activation reduces β-amyloid-induced apoptosis by inhibiting caspase-independent death through phosphatidylinositol 3-kinase signaling. Krantic, S; Mechawar, N; Quirion, R; Yu, W, 2011)	1.09
"Nicotine has been investigated in the gas phase and two conformational forms were characterized through their rotational spectra. "	( Rapid probe of the nicotine spectra by high-resolution rotational spectroscopy. Alonso, JL; Blanco, S; Cabezas, C; Grabow, JU; López, JC; Mata, S; Peña, I, 2011)	2.14
"Nicotine has both unconditioned and conditioned stimulus properties. "	( Conditioned response evoked by nicotine conditioned stimulus preferentially induces c-Fos expression in medial regions of caudate-putamen. Bevins, RA; Charntikov, S; Li, M; Tracy, ME; Zhao, C, 2012)	2.11
"Nicotine has been repeatedly reported as substance possessing neuroprotective properties. "	( Nicotine reduces mortality of developing rats exposed to high-altitude hypoxia and partially suppresses the duration of cortical epileptic afterdischarges. Marešová, D; Pokorný, J; Riljak, V, 2011)	3.25
"Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. "	( Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro. Chen, Q; Cheng, S; Cheng, X; Kou, D; Lu, C; Nie, P; Peng, L; Shen, Y; Wang, W; Xue, E; Ying, X; Zhang, W; Zhang, Y, 2012)	3.26
"Nicotine also has beneficial effects upon cognition, and an emerging literature has demonstrated that it may play a protective or palliative role in diseases such as Alzheimer's disease and schizophrenia."	( Stress and the α7 nicotinic acetylcholine receptor. Hunter, RG, 2012)	1.1
"A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. "	( Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial. Batra, A; Lauri, H; Mann, K; Perfekt, R; Tønnesen, P, 2012)	1.46
"Nicotine has been reported to cause acute toxicity and to present long-term risks, such as chromosomal damage and genetic instability. "	( Mitigation by vitamin C of the genotoxic effects of nicotine in mice, assessed by the comet assay and micronucleus induction. da Silva, J; Kahl, VF; Reyes, JM; Sarmento, MS, 2012)	2.07
"Nicotine has long been recognized as a necessary but insufficient component of tobacco cigarettes to maintain a psychophysiological need to smoke. "	( Denicotinized versus average nicotine tobacco cigarette smoking differentially releases striatal dopamine. Domino, EF; Domino, JS; Evans, C; Guthrie, S; Koeppe, RA; Ni, L; Wang, H; Yang, W; Zubieta, JK, 2013)	2.12
"Nicotine has both rewarding and aversive properties in rodents, as shown by intravenous self-administration, intracranial self-stimulation, and conditioned place preference experiments. "	( Adult mice voluntarily progress to nicotine dependence in an oral self-selection assay. Fryxell, KJ; Locklear, LL; McDonald, CG; Smith, RF, 2012)	2.1
"Nicotine has been implicated as the primary ingredient responsible for these effects."	( The effect of transdermal nicotine on fracture healing in a rabbit model. Donigan, JA; Fredericks, DC; Nepola, JV; Smucker, JD, 2012)	1.4
"Nicotine has analgesic properties and it is hypothesized that cigarette smoking might decrease the dosage of hydrocodone needed for the relief of chronic pain."	( The effect of cigarette smoking on hydrocodone efficacy in chronic pain patients. Ackerman, WE, 2012)	1.1
"Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines."	( Review article: Ulcerative colitis, smoking and nicotine therapy. Leong, RW; Lunney, PC, 2012)	1.36
"Nicotine has been reported to exert certain protective effect in the Parkinson's and Alzheimer's diseases. "	( Nicotine-induced neuroprotection against ischemic injury involves activation of endocannabinoid system in rats. Chen, Y; Dong, H; Lao, N; Nie, H; Sang, H; Tian, L; Tong, L; Xiong, L; Yang, L, 2013)	3.28
"Nicotine has a synergistic effect of arecoline-induced MGMT expression."	( The expression of O(6) -methylguanine-DNA methyltransferase in human oral keratinocytes stimulated with arecoline. Chang, YC; Ho, YC; Hsu, HI; Lee, SS; Tsai, CH; Yu, CC, 2013)	1.11
"Nicotine has been found to induce the proliferation of lung cancer cells through tumor invasion and to confer resistance to apoptosis. "	( Silencing of periostin inhibits nicotine-mediated tumor cell growth and epithelial-mesenchymal transition in lung cancer cells. Bi, AH; Jia, YS; Lin, BH; Luo, LM; Lv, SL; Lv, YE; Wu, SQ, 2013)	2.12
"Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. "	( Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls. Dahmen, N; Drees, J; Ettinger, U; Frommann, I; Heilmann, K; Kessler, H; Landsberg, MW; Lennertz, L; Maier, W; Mössner, R; Petrovsky, N; Quednow, BB; Sträter, B; Wagner, M, 2013)	3.28
"Nicotine has been shown to have effects on anxiety and depression in both human and animal studies. "	( Effect of nicotine and nicotinic receptors on anxiety and depression. Brunzell, DH; Caldarone, BJ; Picciotto, MR, 2002)	2.16
"Nicotine has been considered as the gateway drug, because many teenagers experience cigarette smoking before seeking out other drugs. "	( Chronic continuous nicotine exposure during periadolescence does not increase ethanol intake during adulthood in rats. Chen, WJ; Kelly, RB; Smith, AM, 2002)	2.09
"Nicotine addiction has been identified as the primary contributor to continued widespread tobacco use worldwide. "	( Managing nicotine addiction. Hatsukami, DK; Kotlyar, M, 2002)	2.17
"Nicotine patch therapy has potential benefit for pregnant smokers who continue to smoke despite physician advice to stop."	( Nicotine patch use in pregnant smokers: smoking abstinence and delivery outcomes. Croghan, IT; Hurt, RD; Moyer, TP; Offord, KP; Ogburn, PL; Ramin, KD; Schroeder, DR, 2002)	3.2
"Nicotine has been reported to be therapeutic in some patients with certain neurodegenerative diseases and to have neuroprotective effects in the central nervous system. "	( Nicotine's oxidative and antioxidant properties in CNS. Arendash, GW; Bickford, PC; Newman, MB; Sanberg, PR; Shytle, RD; Tighe, T, 2002)	3.2
"Nicotine has been shown in a variety of studies to improve memory performance. "	( Nicotine interactions with haloperidol, clozapine and risperidone and working memory function in rats. Addy, N; Levin, ED, 2002)	3.2
"Nicotine has been shown to improve attentional performance in all of these disorders."	( Nicotinic receptor subtypes and cognitive function. Levin, ED, 2002)	1.04
"Nicotine has been shown to increase the growth of atherosclerotic lesions."	( Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Aicher, A; Cooke, JP; Dimmeler, S; Heeschen, C; Mohaupt, M; Zeiher, AM, 2003)	2.48
"Nicotine has bimodal effects on anxiety, with low doses having an anxiolytic effect and high doses having an anxiogenic effect. "	( Methyllycaconitine (MLA) blocks the nicotine evoked anxiogenic effect and 5-HT release in the dorsal hippocampus: possible role of alpha7 receptors. File, SE; Genn, RF; Tucci, SA, 2003)	2.04
"Nicotine has been shown to improve performance on attentional tasks in humans with Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder."	( Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats. Levin, ED; Rezvani, AH, 2003)	1.04
"Nicotine has different regional effects on small bowel and colonic cytokine mucosal levels, which might explain some of its opposite effects on small bowel and colonic inflammation."	( Divergent effects of nicotine administration on cytokine levels in rat small bowel mucosa, colonic mucosa, and blood. Eliakim, R; Karmeli, F, 2003)	2.08
"Nicotine has previously been shown to affect both long-term potentiation (LTP) and long-term depression and to reverse age-related impairments of LTP in the hippocampus. "	( The inhibition of long-term potentiation in the rat dentate gyrus by pro-inflammatory cytokines is attenuated in the presence of nicotine. Curran, BP; O'Connor, JJ, 2003)	1.97
"Nicotine has been reported to exert several biological and pharmacological activities in central nervous system. "	( [Changes of serotonergic neurons induced by low dose nicotine in rat forebrain]. Fukui, K; Iizumi, H; Kitabayashi, Y, 2003)	2.01
"Nicotine has been found repeatedly to significantly improve working memory performance in the radial-arm maze."	( NMDA systems in the amygdala and piriform cortex and nicotinic effects on memory function. Levin, ED; May-Simera, H, 2003)	1.04
"Nicotine has been found to effectively increase burst firing of dopaminergic cells."	( Dual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes. Mameli-Engvall, M; Nomikos, GG; Rawal, N; Schilström, B; Svensson, TH, 2003)	1.39
"Nicotine has been demonstrated to enhance learning processes. "	( Nicotine enhances contextual fear conditioning in C57BL/6J mice at 1 and 7 days post-training. Gould, TJ; Higgins, JS, 2003)	3.2
"Nicotine has been studied for the first time by pulse radiolysis techniques. "	( [Study on the chemical activity of nicotine by pulse radiolysis]. Li, WZ; Ni, YM; Sun, XY; Wang, M; Wang, SL, 2003)	2.04
"Nicotine has been shown to have additive as well as antagonistic effects on behavior stimulated by ethanol. "	( Nicotine and ethanol enhancements of acoustic startle reflex are mediated in part by dopamine in C57BL/6J mice. Gould, TJ; Lewis, MC, 2003)	3.2
"Nicotine has been tested in the conventional mouse bone marrow assay. "	( Nicotine is not clastogenic at doses of 1 or 2 mg/kg body weight given orally to male mice. Adler, ID; Attia, SM, 2003)	3.2
"Nicotine has many acute subjective, physiological, and behavioral effects in humans, some of which may explain why nicotine produces dependence. "	( The consistency of acute responses to nicotine in humans. Conklin, CA; Fonte, C; Jetton, C; Perkins, KA; Stolinski, A, 2003)	2.03
"Nicotine has analgesic actions in experimental animals and humans. "	( Sucrose consumption enhances the analgesic effects of cigarette smoking in male and female smokers. Carrington, C; Kanarek, RB, 2004)	1.77
"Nicotine has been shown to release nitric oxide from nerves in human sigmoid colon. "	( Differential effect of nitric oxide synthase inhibition on sigmoid colon longitudinal and circular muscle responses to nicotine and nerve stimulation in vitro. Green, JT; Marshall, RW; McKirdy, HC; Rhodes, J; Richardson, CE; Williams, GT, 2004)	1.97
"Nicotine has all the desirable characteristics of an ETS marker. "	( [Nicotine measurement as an airborne marker of environmental tobacco smoke]. López, MJ; Nebot, M, 2003)	2.67
"Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimer's and Parkinson's disease groups."	( Nicotine improves delayed recognition in schizophrenic patients. Avila, MT; Blaxton, TA; Kakoyannis, AN; Myers, CS; Robles, O; Sherr, JD; Thaker, GK, 2004)	3.21
"Nicotine itself has quite complex actions, mediated in part by nicotinic cholinergic receptors that may have extraneuronal, as well as neuronal distribution."	( Nicotine and angiogenesis: a new paradigm for tobacco-related diseases. Bitterman, H; Cooke, JP, 2004)	2.49
"Nicotine has a powerful preventive effect on neuroleptic-induced dopamine D2 receptor upregulation in the rat. "	( Does nicotine affect D2 receptor upregulation? A case-control study. Negrete, JC; Seeman, MV; Seeman, P; Shammi, CM; Silvestri, S, 2004)	2.28
"Nicotine has been documented to regulate the release of plasma arginine vasopressin (AVP). "	( Nicotine replacement therapy-associated syndrome of inappropriate antidiuretic hormone. Andrus, MR; Curry, WA; Finch, CK, 2004)	3.21
"Nicotine has been shown to affect a wide variety of biological functions ranging from gene expression, regulation of hormone secretion and enzyme activities."	( Nicotine, its metabolism and an overview of its biological effects. Yildiz, D, 2004)	2.49
"Nicotine has an overall detrimental effect on NP disc cells cultured in vitro. "	( Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Akmal, M; Anand, B; Goodship, A; Kesani, A; Singh, A; Wiseman, M, 2004)	2.17
"Nicotine has many acute and chronic pharmacological effects. "	( [Calcium signaling mediated by nicotine receptors in neurons]. Nakashima, T; Nakayama, H, 2004)	2.05
"Nicotine has been reported to normalize deficits in auditory sensory gating in the cases of schizophrenia, suggesting an involvement of nicotinic acetylcholine receptors in attentional abnormalities. "	( Nicotine blocks apomorphine-induced disruption of prepulse inhibition of the acoustic startle in rats: possible involvement of central nicotinic alpha7 receptors. Araki, H; Choshi, T; Gomita, Y; Hibino, S; Shibata, K; Suemaru, K; Umeda, K; Yasuda, K, 2004)	3.21
"Nicotine also has a neuroprotective action."	( Smoking, nicotine and Parkinson's disease. Quik, M, 2004)	1.46
"Nicotine has been shown to induce relaxation via nitric oxide (NO) production with activation of endothelium nitric oxide synthase (eNOS), however the effect of nicotine on lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced NO production and inducible NOS (iNOS) gene expression is still undefined. "	( Nicotine enhancement of lipopolysaccharide/interferon-gamma-induced cytotoxicity with elevating nitric oxide production. Chen, YC; Lee, TJ; Lin, HY; Shen, SC; Tsai, SH, 2004)	3.21
"Nicotine has been reported to have neuroprotective effects. "	( Protective effect of nicotine on tunicamycin-induced apoptosis of PC12h cells. Ikeuchi, T; Kishi, S; Nakayama, H; Sasaya, H; Shimoke, K; Utsumi, T, 2004)	2.09
"Nicotine has been shown in numerous previous studies to significantly improve memory on the radial-arm maze, yet the critical mechanisms underlying this effect are not fully characterized. "	( Baclofen interactions with nicotine in rats: effects on memory. Icenogle, L; Levin, ED; Weber, E, 2004)	2.06
"Nicotine has been reported to regulate food intake and body weight. "	( Nicotine stimulates prolactin-releasing peptide (PrRP) cells and non-PrRP cells in the solitary nucleus. Adachi, S; Fujiwara, K; Inoue, K; Nemoto, H; Sun, B, 2005)	3.21
"Nicotine has also been shown to exert positive effects on certain neurotrophins such as nerve growth factor (NGF), and therefore could play a role beyond mere symptomatic therapy."	( Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor. Hernandez, CM; Terry, AV, 2005)	1.47
"Nicotine has been shown to be implicated in the pathophysiology of psychiatric disorders as schizophrenia or Alzheimer's disease, and has also been proposed as a self-administered drug in schizophrenia."	( Transdermal nicotine administration enhances automatic auditory processing reflected by mismatch negativity. Arai, H; Inami, R; Inoue, R; Kirino, E, 2005)	1.43
"Nicotine has been shown to promote the release of a variety of neurotransmitters including glutamate."	( Chronic nicotine and dizocilpine effects on regionally specific nicotinic and NMDA glutamate receptor binding. Caldwell, DP; Getachew, B; Levin, ED; Petro, A; Rezvani, AH; Tizabi, Y, 2005)	1.48
"Nicotine has roles in the addiction to smoking, replacement therapy for smoking cessation, as a potential medication for several diseases such as Parkinson's disease, Alzheimer's disease, and ulcerative colitis. "	( Interindividual variability in nicotine metabolism: C-oxidation and glucuronidation. Nakajima, M; Yokoi, T, 2005)	2.06
"Nicotine has been shown in many, but not all, studies to improve cognitive function in a number of species including rats, mice, monkeys, and humans. "	( Timing of nicotine effects on learning in zebrafish. Levin, ED; Limpuangthip, J; Peterson, M; Rachakonda, T, 2006)	2.18
"Nicotine has been shown in a variety of studies in humans and experimental animals to improve cognitive function. "	( Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Levin, ED; McClernon, FJ; Rezvani, AH, 2006)	1.78
"Nicotine has a long and storied history in physiology and pharmacology. "	( Nicotine psychopharmacology research contributions to United States and global tobacco regulation: a look back and a look forward. Henningfield, JE; Zeller, M, 2006)	3.22
"Nicotine also has the capacity to concentrate in the fetus, regardless of exposure source."	( Environmental tobacco smoke and sudden infant death syndrome: a review. Adgent, MA, 2006)	1.06
"The nicotine inhaler has been tested as safe and efficacious in the treatment of tobacco cessation. "	( The use of the nicotine inhaler in smoking cessation. Burkett, JS, 2006)	1.24
"Nicotine has been shown to specifically reduce reaction times to invalidly cued targets in spatial cueing paradigms. "	( Effects of nicotine on visuo-spatial selective attention as indexed by event-related potentials. Fink, GR; Meinke, A; Thiel, CM, 2006)	2.17
"Nicotine has been shown to activate stress-related brain nuclei, including the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CEA), through complex mechanisms involving direct and indirect pathways. "	( Nicotine modulation of stress-related peptide neurons. Cheng, MY; Islas, MI; Lee, AG; Leslie, FM; Loughlin, SE; Villegier, AS, 2006)	3.22
"Nicotine has been shown to produce some beneficial effects in neurodegenerative disorders, and several studies have suggested that these effects may be mediated in part through the action of the neurotrophic factor BDNF. "	( Nicotine regulates SH-SY5Y neuroblastoma cell proliferation through the release of brain-derived neurotrophic factor. Carney, SL; Serres, F, 2006)	3.22
"Nicotine has been shown to enhance specific working memory processes in healthy adults."	( The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine. Hutton, SB; Rusted, JM; Rycroft, N, 2006)	1.27
"Nicotine has been shown in our studies to reverse the memory impairment caused by acute clozapine-induced memory improvement."	( Nicotinic-antipsychotic drug interactions and cognitive function. Levin, ED; Rezvani, AH, 2006)	1.06
"Nicotine and serotonin have been reported to regulate cytokine release."	( Nicotine and serotonin in immune regulation and inflammatory processes: a perspective. Changeux, JP; Cloëz-Tayarani, I, 2007)	2.5
"Nicotine has acute vasoconstrictive properties, diminishing blood flow and increasing the risk of flap necrosis."	( Transcutaneous electrical nerve stimulation in viability of a random skin flap in nicotine-treated rats. Ferreira, LM; Gomes, HC; Leite, MT; Russo, CR, 2006)	1.28
"Nicotine has a therapeutic benefit in treating Alzheimer's disease (AD). "	( Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model. Chen, Q; Liu, Q; Qin, C; Zhang, J; Zhao, B; Zhu, H, 2007)	2.06
"Nicotine metabolism has been hypothesized to affect patterns of smoking. "	( Urine nicotine metabolites and smoking behavior in a multiracial/multiethnic national sample of young adults. Benowitz, NL; Hu, MC; Kandel, DB; Schaffran, C; Udry, JR, 2007)	2.26
"Nicotine has been shown to exert negative effects on bone. "	( Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats. Ima-Nirwana, S; Lee, PL; Lukman, HI; Nazrun, AS; Norazlina, M, 2007)	2.03
"Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. "	( Nicotine lozenges for the treatment of smokeless tobacco use. Croghan, IT; Dale, LC; Ebbert, JO; Hurt, RD; Rasmussen, DF; Schroeder, DR; Severson, H; Vander Weg, MW, 2007)	3.23
"Nicotine has been postulated to be a possible neuroprotective agent in Alzheimer's Disease (AD). "	( Beta-amyloid blocks high frequency stimulation induced LTP but not nicotine enhanced LTP. Anwyl, R; Rowan, MJ; Welsby, PJ, 2007)	2.02
"Nicotine has marked effects on sleep, arousal and body weight. "	( Nicotine treatment regulates neuropeptide S system expression in the rat brain. Diéguez, C; González, CR; Lage, R; López, M, 2007)	3.23
"Nicotine has been found to improve antisaccade performance in patients with schizophrenia and healthy controls."	( Non-cholinergic modulation of antisaccade performance: a modafinil-nicotine comparison. Clowry, O; Groomsbridge, C; Hutton, SB; Rusted, JM; Rycroft, N; Sierakowski, A, 2007)	1.3
"Nicotine has been demonstrated to stimulate postnatal angiogenesis, having an antiapoptotic effect on endothelial cells. "	( Nicotine enlivenment of blood flow recovery following endothelial progenitor cell transplantation into ischemic hindlimb. Asahara, T; Eguchi, M; Iwaguro, H; Masuda, H; Sugimoto, A; Tanabe, T, 2007)	3.23
"Nicotine also has the ability to affect synaptic function via mechanisms that remain partially unknown."	( Nicotine regulates multiple synaptic proteins by inhibiting proteasomal activity. De Biasi, M; Rezvani, K; Shim, D; Teng, Y, 2007)	2.5
"Nicotine has been shown to improve acoustic PPI in some animal strains and in humans."	( Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients. Hong, LE; Lewis, J; Thaker, GK; Wonodi, I, 2008)	2.51
"Nicotine has wellknown, unpleasant side effects, e.g., transient dizziness, nausea, and nicotine-induced nystagmus (NIN). "	( The effect of nicotine on perceptual, ocular motor, postural, and vegetative functions at rest and in motion. Brandt, T; Denecke, K; Elfont, R; Glasauer, S; Jahn, K; Krafczyk, S; Krams, M; Strupp, M; von Meyer, L; Zingler, VC, 2007)	2.14
"Nicotine chewing gum has been available since 1982, when it was shown to increase smoking cessation rates by approximately 1.5- to 2-fold after 12 months. "	( Which is the best primary medication for long-term smoking cessation--nicotine replacement therapy, bupropion or varenicline? Doggrell, SA, 2007)	2.02
"Nicotine has important psychotoxic activity but comparing to alcohol and heroin it doesn't determine social disintegrate."	( [Nicotine addiction--diagnosis and treatment]. Didilescu, C; Munteanu, I, )	1.76
"Nicotine has been shown to improve various aspects of cognitive processing such as attention and memory, however, its effects on lexical-semantic processing are relatively uncharted. "	( Transdermal nicotine modulates strategy-based attentional semantic processing in non-smokers. Chenery, HJ; Copland, DA; Holmes, AD, 2008)	2.17
"Nicotine has been shown to stimulate the production of HIV-1 by in vitro-infected alveolar macrophages, and the HIV-1 protein gp120 binds to nicotinic receptors."	( Potentiation of HIV-1 expression in microglial cells by nicotine: involvement of transforming growth factor-beta 1. Aravalli, RN; Gekker, G; Hu, S; Peterson, PK; Rock, RB; Sheng, WS, 2008)	1.31
"Nicotine has been implicated as a cocarcinogen that promotes lung cancer development through prosurvival pathways."	( Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells. Chen, RJ; Guo, HR; Ho, YS; Wang, YJ, 2008)	1.33
"Nicotine has been, however, reported to induce little drinking behavior."	( Effect of central nicotinic activation on drinking behavior. Hirase, M; Inenaga, K; Kai, A; Ono, K, 2008)	1.07
"Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status."	( Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis. Bülow, J; Gottrup, F; Hemmingsen, U; Jørgensen, S; Loft, S; Petersen, LJ; Sørensen, LT, 2009)	2.14
"A nicotine gum has been approved as a prescription drug to help smokers stop smoking. "	( Nicotine gum to help stop smoking. Hughes, JR; Miller, SA, )	2.3
"Nicotine has been found to suppress aggressive behavior in ants (Kostowski 1968), rats (Silverman 1971), and cats (Berntson et."	( Effects of cigarette smoking on human aggressive behavior. Cherek, DR, 1984)	0.99
"Nicotine has been implicated as a causative factor in the intrauterine growth retardation associated with smoking in pregnancy. "	( Maternal adipose tissue response to nicotine administration in the pregnant rat: effects on fetal body fat and cellularity. Kanagasabai, T; Williams, CM, 1984)	1.99
"Nicotine and cotinine have been determined in plasma samples from 87 beagle dogs chronically exposed to cigarette smoke with three different levels of nicotine. "	( Plasma nicotine and cotinine in tobacco smoke exposed beagle dogs. Auerbach, O; Brazell, RS; Henderson, GM; Jenkins, RA; Romig, PL; Stiff, AC, 1984)	2.17
"Nicotine chewing-gum has recently become available to doctors in Britain for use as an aid to giving up smoking. "	( Clinical use of nicotine chewing-gum. Jarvis, MJ; Raw, M; Russell, MA, 1980)	2.05
"Nicotine itself has little effect on the evoked DA release."	( [Chronic treatment with nicotine enhances the sensitivity of dopamine autoreceptors that modulate dopamine release from the rat striatum]. Takaki, T, 1995)	1.32
"Nicotine has been found to improve memory performance in a variety of tests in rats, monkeys, and humans. "	( Acute and chronic nicotinic interactions with dopamine systems and working memory performance. Levin, ED; Rose, JE, 1995)	1.73
"Nicotine gum has been shown to be effective in improving abstinence rates, and in reducing post-cessation withdrawal distress and weight gain. "	( Dose effects of nicotine gum. Gross, J; Johnson, J; Sigler, L; Stitzer, ML, )	1.92
"Nicotine has been found to improve memory performance in a variety of tests, including the radial-arm maze. "	( Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze. Abood, L; Levin, ED; Rose, JE, )	1.57
"Nicotine dependence has a biological substratum defined as "neuroadaptation to nicotine." 2."	( Nicotine-related brain disorders: the neurobiological basis of nicotine dependence. Ochoa, EL, 1994)	2.45
"Nicotine has been shown to possess some neuroprotective properties for both cholinergic and dopaminergic neurons."	( Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: emphasis on Alzheimer's disease and Parkinson's disease. James, JR; Nordberg, A, 1995)	1.01
"Nicotine has been reported to increase or decrease measures of activity in rats, including locomotor activity and rearing. "	( Acute and chronic nicotine effects on measures of activity in rats: a multivariate analysis. Ksir, C, 1994)	2.07
"Nicotine has also been shown to improve performance in some cognitive tests in patients with Alzheimer's disease."	( Caffeine and nicotine improve visual tracking by rats: a comparison with amphetamine, cocaine and apomorphine. Evenden, JL; Jennings, C; Oliver, L; Turpin, M, 1993)	1.38
"Nicotine has been shown to increase the levels of intracellular free Ca through both nAChR types."	( [Molecular diversity and properties of brain nicotinic acetylcholine receptor]. Nakashima, T; Nakayama, H; Okuda, H, 1994)	1.01
"Nicotine has a biphasic effect on sleep: at low concentrations, it leads to relaxation and sedation and at high concentrations inhibits sleep."	( [Prevention and treatment of sleep disorders through regulation] of sleeping habits]. Bailly, D; Onen, F; Onen, SH; Parquet, P, 1994)	1.01
"Nicotine has been shown to stimulate neurotransmitter release from brain tissue by acting on presynaptic receptors. "	( Characterization of nicotine-induced desensitization of evoked dopamine release from rat striatal synaptosomes. Hillebrand, JA; Rowell, PP, 1994)	2.05
"Nicotine has been found in a variety of studies to improve performance in memory tasks. "	( Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection. Briggs, SJ; Christopher, NC; Levin, ED; Rose, JE, 1993)	2.16
"Nicotine has enormous therapeutical implications."	( [Neuroleptics and nicotine]. Erdmann, R, 1995)	1.35
"Nicotine has a similar effect on the coronary circulation."	( Recent problems with paracervical vasopressin: a possible synergistic reaction with nicotine. Groudine, SB; Morley, JN, 1996)	1.24
"Nicotine has been shown to affect both of these factors."	( The maternal and fetal physiologic effects of nicotine. Clark, KE; Lambers, DS, 1996)	1.27
"Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs."	( Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Levin, ED; McEvoy, J; Rose, JE; Wilson, W, 1996)	2.46
"Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function."	( In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Feyerabend, C; Madretsma, S; Tak, CJ; van Dijk, JP; Wilson, JH; Wolters, LM; Zijlstra, FJ, 1996)	2.07
"Nicotine has been shown to decrease these two symptoms as well as reduce the frequency and duration of apneas."	( Is sleep apnea a predisposing factor for tobacco use? Schrand, JR, 1996)	1.02
"Nicotine has various effects in the CNS, especially in dopaminergic and cholinergic systems, relevant in pathophysiology of neuropsychiatric movement disorders. "	( [Nicotine in neuropsychiatric movement disorders]. Erdmann, R, 1996)	2.65
"Pure nicotine has no known carcinogenic properties and can be administered in numerous ways including transdermal patches and tablets."	( Does nicotine have beneficial effects in the treatment of certain diseases? Birtwistle, J; Hall, K, )	1.1
"Nicotine has toxic effects on peripheral, circulation, which cause gingival vasoconstriction."	( Tobacco smoking and periodontal diseases. Matthews, DC; Qandil, R; Sandhu, HS, 1997)	1.02
"Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. "	( Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition. Goldberg, SR; Schindler, CW; Shoaib, M, 1997)	3.18
"Nicotine has been found to improve cognitive performance in a variety of tasks including the radial maze. "	( Chronic haloperidol administration does not block acute nicotine-induced improvements in radial-arm maze performance in the rat. Levin, ED, 1997)	1.99
"[3H]nicotine has been used as a photoaffinity agonist to identify amino acids within the Torpedo nicotinic acetylcholine receptor (nAChR) gamma-subunit that contributes to the structure of the agonist binding site. "	( Identification of tryptophan 55 as the primary site of [3H]nicotine photoincorporation in the gamma-subunit of the Torpedo nicotinic acetylcholine receptor. Chiara, DC; Cohen, JB; Middleton, RE, 1998)	1.1
"Nicotine has been shown to delay the developmental increase of muscarinic receptors in brain of rat neonates. "	( Nicotine administration decreases the number of binding sites and mRNA of M1 and M2 muscarinic receptors in specific brain regions of rat neonates. Konishi, Y; Mayumi, M; Muramatsu, I; Taniguchi, T; Zhu, J, 1998)	3.19
"Nicotine not only has cytotoxicity to vascular vessel but also results in vasoconstrictor effects which depend upon endothelium intact, probably by inhibiting the release of endothelium-derived relaxing factor."	( [Injury effects of nicotine on isolated rat common carotid artery]. Gu, Y; Wang, T; Wu, G, 1997)	2.07
"Nicotine has been shown to be a potent stimulus for the secretion of the stress-responsive hormones, adrenocorticotropin (ACTH) and prolactin. "	( Response of the hypothalamo-pituitary-adrenal axis to nicotine. Fu, Y; Matta, SG; Sharp, BM; Valentine, JD, 1998)	1.99
"Nicotine has many effects on CNS functions, presumably through its action on neuronal nicotinic acetylcholine receptors (AChRs). "	( Nicotinic receptor-induced apoptotic cell death of hippocampal progenitor cells. Berger, F; Gage, FH; Vijayaraghavan, S, 1998)	1.74
"Nicotine use has been associated with augmented dopaminergic neurotransmission within the central nervous system by a number of researchers. "	( Acute nicotine pretreatment augments dopaminergic pulmonary vasodilation. Russ, RD, 1998)	2.22
"Nicotine has been found repeatedly to significantly improve working memory performance in the radial-arm maze."	( Nicotine-dizocilpine interactions and working and reference memory performance of rats in the radial-arm maze. Bettegowda, C; Christopher, NC; Levin, ED; Weaver, T, 1998)	2.46
"Nicotine has been identified as the cause of tobacco dependence."	( Nicotine replacement therapy. Hunter, DA; Thompson, GH, 1998)	2.46
"Nicotine has been shown to affect attentional and mnemonic processes. "	( Effects of cigarette smoking and 12-h abstention on working memory during a serial-probe recognition task. Herrera, C; Kang, C; Pineda, JA; Sandler, A, 1998)	1.74
"Nicotine has been shown to improve attentiveness in smokers and attenuate attentional deficits in Alzheimer's disease patients, schizophrenics and adults with attention-deficit/hyperactivity disorder (ADHD). "	( Transdermal nicotine effects on attention. Conners, CK; Hinton, SC; Levin, ED; March, J; Meck, WH; Rose, JE; Silva, D, 1998)	2.12
"Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated."	( Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis. Cohen, P; Eliakim, R; Fich, A; Karmeli, F; Rachmilewitz, D, 1998)	2.08
"Nicotine has been suggested to have cognitive enhancing effects. "	( Nicotine enhancement of contextual fear conditioning. Gould, TJ; Wehner, JM, 1999)	3.19
"Nicotine has been tested in 3 different concentrations: 6 microg/ml; 60 microg/ml; 600 microg/ml."	( The effects of nicotine and age on replication and viability of human gingival fibroblasts in vitro. Checchi, L; Ciapetti, G; Monaco, G; Ori, G, 1999)	1.38
"Nicotine has a wide range of biological effects, and proteases have been extensively studied for their biological roles in living creatures. "	( Protease activity induced by nicotine in human cells. Chi, XJ; Hasegawa, R; Kita, K; Nakajima, N; Suzuki, N; Takahashi, S; Tanzawa, H; Wang, XL; Yamamori, H; Yokoe, H, 1999)	2.04
"Nicotine has been reported to have positive effects on motor performance in patients with Parkinson's disease. "	( Worsening of motor performance in patients with Parkinson's disease following transdermal nicotine administration. Ebersbach, G; Müller, J; Poewe, W; Stöck, M; Wenning, G; Wissel, J, 1999)	1.97
"Nicotine has been shown to depolarize membrane potential and to lengthen action potential duration in isolated cardiac preparations. "	( Direct block of inward rectifier potassium channels by nicotine. Wang, H; Wang, Z; Xu, D; Yang, B; Zhang, L, 2000)	2
"Nicotine has proven to be a useful prototypic compound for the family of nicotinic compounds."	( Development of nicotinic drug therapy for cognitive disorders. Levin, ED; Rezvani, AH, 2000)	1.03
"Nicotine itself has been shown to improve memory-related task performance in aged animals and in AD patients."	( Differential improvement in memory-related task performance with nicotine by aged male and female rhesus monkeys. Buccafusco, JJ; Jackson, WJ; Jonnala, RR; Terry, AV, 1999)	1.26
"Nicotine also has effects on other transmitters like serotonin (5HT), dopamine, or GABA."	( Nicotine for Alzheimer's disease. López-Arrieta, JM; Rodríguez, JL; Sanz, F, 2000)	2.47
"Nicotine has been shown to decrease reaction time and increase anticipatory responses in a five-choice serial reaction time task (5-CSRTT) in rats, but the receptor mechanisms mediating this effect remain unknown."	( Characterisation of the effects of nicotine in the five-choice serial reaction time task in rats: antagonist studies. Blondel, A; Moser, PC; Sanger, DJ, 2000)	2.03
"Nicotine has a multitude of biological actions in the central and peripheral nervous systems where nicotinic acetylcholine receptors are found. "	( Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines. Friedman, H; Hakki, A; Hallquist, N; Pross, S; Wecker, L, 2000)	2.06
"Nicotine has long been known to interact with nicotinic acetylcholine (ACh) receptors since Langley used it extensively to chart sympathetic ganglia a century ago. "	( Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Aistrup, GL; Fenster, CP; Lester, RA; Levin, ED; Marszalec, W; Martin, BR; Narahashi, T; Quick, MW; Sattelle, DB, 2000)	2.01
"Nicotine gum therapy has been found to reduce weight gain in the first months after cessation, but its long-term effects are not fully known."	( Long-term effects of nicotine gum on weight gain after smoking cessation. Garvey, AJ; Kinnunen, T; Nordstrom, BL; Utman, CH, 1999)	1.34
"Nicotine has been reported to potentiate the cataleptic effect of the dopamine receptor antagonist haloperidol in rats. "	( Enhancement of haloperidol-induced catalepsy by nicotine: an investigation of possible mechanisms. Boye, SM; Clarke, PB, 2000)	2.01
"Nicotine has been shown to be effective as a treatment for reducing tobacco dependence. "	( Nornicotine pretreatment decreases intravenous nicotine self-administration in rats. Bardo, MT; Crooks, PA; Dwoskin, LP; Green, TA; Phillips, SB, 2000)	2.37
"Nicotine has opposite effects on iodoacetamide-induced colitis and jejunitis, which may be partly explained by decreased PGE2 generation and increased NOS activity in the jejunum and an increase in the colonic microcirculation."	( Dual effect of chronic nicotine administration: augmentation of jejunitis and amelioration of colitis induced by iodoacetamide in rats. Cohen, P; Eliakim, R; Heyman, SN; Karmeli, F; Rachmilewitz, D, 2001)	1.34
"Nicotine has dose-dependent effects on colonic motor activity in healthy subjects."	( Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Bharucha, AE; Burton, D; Camilleri, M; Coulie, B; Sandborn, WJ, 2001)	1.26
"Nicotine has weak but reliable conditioning effects, and the brain region mediating those effects of nicotine involves the ventral tegmental area."	( Neurobiological mechanisms of nicotine craving. Miyata, H; Yanagita, T, 2001)	1.32
"Nicotine has been shown in animals to stimulate the release of dopamine in the striatum, and to preserve nigral neurons and striatal dopamine levels in laboratory animals with lesioned nigrostriatal pathways."	( Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Petrovitch, H; Ross, GW, 2001)	1.29
"Nicotine has been reported to reduce anxiety in humans and in a number of animal tests. "	( Antagonism of the anxiolytic effect of nicotine in the dorsal raphe nucleus by dihydro-beta-erythroidine. Cheeta, S; File, SE; Tucci, S, 2001)	2.02
"Nicotine has been found to improve cognitive functions in patients with Alzheimer's disease, but little is known about its effects in the healthy non-smoking elderly."	( Effects of transdermal nicotine on attention and memory in healthy elderly non-smokers. Ko, RW; Min, SK; Moon, IW; Shin, HS, 2001)	2.06
"Nicotine has been previously shown to have immunosuppressive actions. "	( Nicotine reduces the incidence of type I diabetes in mice. Mabley, JG; Pacher, P; Salzman, AL; Southan, GJ; Szabó, C, 2002)	3.2
"Nicotine has full efficacy on the alpha4beta2 nAChR and partial efficacy on the alpha3beta2 nAChR."	( First and second transmembrane segments of alpha3, alpha4, beta2, and beta4 nicotinic acetylcholine receptor subunits influence the efficacy and potency of nicotine. Kuryatov, A; Lindstrom, J; Nelson, ME; Rush, R, 2002)	1.23
"Nicotine has been found to be effective in attenuating memory deficits resulting from lesions of the septohippocampal pathway or aging in experimental animals."	( Nicotinic systems and cognitive function. Levin, ED, 1992)	1
"Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. "	( Persistence of chronic nicotine-induced cognitive facilitation. Briggs, SJ; Christopher, NC; Levin, ED; Rose, JE, 1992)	2.04
"Nicotine has been hypothesized to induce neurobehavioral teratology by mimicking prematurely the natural developmental signals ordinarily communicated by the ontogeny of cholinergic synaptic transmission. "	( Deficits in development of central cholinergic pathways caused by fetal nicotine exposure: differential effects on choline acetyltransferase activity and [3H]hemicholinium-3 binding. Lappi, SE; McCook, EC; Seidler, FJ; Slotkin, TA; Yanai, J; Zahalka, EA, )	1.81
"Nicotine has a small molecular weight and is absorbed via the mucosa (Guccal or nasal), the pulmonary alveoli and the skin. "	( [Pharmacology of nicotine]. Bourlaud, I; Patte, F; Perault, MC; Underner, M, 1992)	2.07
"Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. "	( Arterial blood nicotine concentration and coronary vasoconstrictive effect of low-nicotine cigarette smoking. Kostis, JB; Kumar, A; Lacy, CR; Moreyra, AE; Wilson, AC, 1992)	1.19
"Nicotine dependence has been clearly documented as an addiction to nicotine. "	( Nicotine dependence: diagnosis, pharmacology and treatment. Cocores, JA; Miller, NS, 1991)	3.17
"Nicotine replacement has been shown to be a safe and effective pharmacological treatment for tobacco dependence in certain smokers."	( Antismoking products. Gourlay, SG; McNeil, JJ, )	0.85
"Thus nicotine has a detrimental effect on the development of newborn offspring in general and incisor development in particular."	( Postnatal effects of nicotine on incisor development of albino mouse. Saad, AY, 1990)	1.05
"Nicotine, which has some clinical anxiolytic action, registered a small true positive."	( The staircase test: some evidence of nonspecificity for anxiolytics. Howard, JL; Pollard, GT, 1986)	0.99
"A nicotine chewing gum has recently become available for use as an aid in giving up cigarette smoking. "	( Cost-effectiveness of nicotine gum as an adjunct to physician's advice against cigarette smoking. Colditz, GA; Delea, TE; Huse, DM; Oster, G, 1986)	1.31
"Nicotine gum has potential as substitution therapy for prolonged treatment in a highly addictive, compulsive patient."	( Nicotine gum dependency: a positive addiction. Mulry, JT, 1988)	2.44
"Nicotine has been shown to transfer across the placenta and into breast milk in humans."	( Clinical pharmacokinetics of nicotine. Svensson, CK, 1987)	1.29
"Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. "	( Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects. Aubert, JF; Brunner, HR; Burnier, M; Nussberger, J; Waeber, B, 1987)	3.16

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Nicotine appears to activate specific intracellular death-related pathways, probably by bax-dependent activation of caspase-3. Exposure promotes hippocampal gamma oscillations in a methyllycaconitine-sensitive manner. Nicotine can enhance contextual learning while ethanol impairs some forms of learning.

Excerpt	Reference	Relevance
"The nicotine group had lower FA and higher RD limited to the anterior limb of the internal capsule."	( White matter microstructure differences in individuals with dependence on cocaine, methamphetamine, and nicotine: Findings from the ENIGMA-Addiction working group. Alia-Klein, N; Allgaier, N; Cao, Z; Conrod, P; Cupertino, RB; Ekhtiari, H; Fouche, JP; Garavan, H; Goldstein, RZ; Hahn, S; Jahanshad, N; Li, CR; Lochner, C; London, ED; Luijten, M; Mackey, S; Masjoodi, S; Momenan, R; Oghabian, MA; Ottino-González, J; Roos, A; Schwab, N; Stein, DJ; Stein, EA; Thompson, PM; Uhlmann, A; Veltman, DJ; Verdejo-García, A; Zhang, S; Zhao, M; Zhong, N, 2022)	1.42
"Nicotine plays a role in inhibiting inflammatory factors, which contributes to improving cognitive impairment by activating α"	( Nicotine Activating α Diao, Y; Gou, J; Guo, S; Han, T; Lai, R; Wang, Q; Wei, F; Yin, Y; Zhang, D, 2022)	3.61
"Nicotine did not enhance delay cued fear."	( The effect of acute nicotine administration on human delay cued and context fear conditioning. Astur, RS; Gould, TJ; Palmisano, AN, 2023)	1.96
"Nicotine can produce antinociception in preclinical pain models; however, the ability of nicotine to augment the antinociceptive effects of opioid agonists has not been investigated. "	( Enhancement of Opioid Antinociception by Nicotine. Barreto de Moura, F; Bergman, J; Withey, SL, 2019)	2.22
"Nicotine can enhance proliferation, migration and invasion of tongue squamous cell carcinoma Cal27 cells by activating Wnt signaling pathway."	( [Biological effect of nicotine on Cal27 cell line in patients with tongue squamous cell carcinoma]. Duan, XF; He, J; Kang, JY, 2019)	2.27
"Nicotine is able to increase the number of S."	( In vitro Cariostatic effects of cinnamon water extract on nicotine-induced Streptococcus mutans biofilm. Alshahrani, AM; Gregory, RL, 2020)	1.52
"Nicotine exposure can increase oxidative stress levels, which could lead to thyroid dysfunction."	( Thyroid redox imbalance in adult Wistar rats that were exposed to nicotine during breastfeeding. de Andrade, CBV; de Faria, CC; de Moura, EG; de Oliveira, E; Fortunato, RS; Lisboa, PC; Lopes, BP; Manhães, AC; Miranda, RA; Peixoto, TC; Soares, PN, 2020)	1.52
"This nicotine-induced increase does not appear to be mediated by HIF-1α, since HIF-1α was stabilized by force application and hypoxia, but not by nicotine."	( The role of HIF-1α in nicotine-induced root and bone resorption during orthodontic tooth movement. Bauer, M; Deschner, J; Jantsch, J; Kirschneck, C; Proff, P; Schröder, A; Spanier, G; Ullrich, N, 2021)	1.39
"Nicotine may increase pain hypersensitivity by promoting the expression of P2X4R, BDNF, and IL-1β through modulation of IRF8 levels in microglial cells."	( Nicotine induces P2X4 receptor, interleukin-1 beta, and brain-derived neurotrophic factor expression in BV2 microglia cells. Guo, L; Lv, Q; Zhang, Y; Zhang, Z, 2020)	3.44
"Nicotine blocked increase in locomotor activity, decrease in social interaction time, and prolonged immobility in a forced swimming test, but it did not decrease sucrose preference in the KMO KO mice."	( Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid. Fujigaki, H; Fujigaki, S; Hasegawa, M; Hirakawa, M; Hoshi, M; Kosuge, A; Kubota, H; Kunisawa, K; Kurahashi, H; Mori, Y; Mouri, A; Murakami, R; Nabeshima, T; Nakano, T; Niijima, M; Saito, K; Yamamoto, Y, 2021)	1.34
"Nicotine may also activate thyroid receptor signaling pathways to improve memory impairment caused by hypothyroidism."	( Molecular insights into the benefits of nicotine on memory and cognition (Review). Alhowail, A, 2021)	1.61
"Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines."	( From nicotine to the cholinergic anti-inflammatory reflex - Can nicotine alleviate the dysregulated inflammation in COVID-19? Ashby, CR; Daley, LA; Gauthier, AG; Kennedy, TP; Lin, M; Mantell, LL; Wu, J, 2021)	1.86
"Nicotine did not inhibit Aβ aggregation in vitro, however it suppressed Aβ deposits and reduced the Aβ oligomers to alleviate the toxicity induced by Aβ overexpression in C."	( Nicotine prevents in vivo Aβ toxicity in Caenorhabditis elegans via SKN-1. Jin, Y; Li, H; Lu, X; Wang, X; Zhang, Y; Zhao, L, 2021)	2.79
"Nicotine could increase autophagy level of hPDLCs, thus affecting the occurrence and development of smoking related periodontitis."	( [A preliminary study on the autophagy level of human periodontal ligament cells regulated by nicotine]. Lizheng, W; Lulu, W; Shuai, Y; Xiaojing, W; Xing'an, W; Yang, D; Zhifei, Z, 2017)	2.12
"Nicotine exposure can increase the expression of conditioned responses, and we hypothesized that animals exposed to nicotine would also exhibit less flexible conditioned responses after a change in the expected unconditioned stimulus."	( Nicotine-enhanced Pavlovian conditioned approach is resistant to omission of expected outcome. Boettiger, CA; Robinson, DL; Stringfield, SJ, 2018)	2.64
"Nicotine can enhance attention and attribution of incentive salience to nicotine-associated stimuli. "	( Attentional capacities prior to drug exposure predict motivation to self-administer nicotine. Cador, M; Caille, S; Dellu-Hagedorn, F; Noe, E; Vandaele, Y, 2018)	2.15
"Nicotine intake can cause micro-structural changes of the bone, decreased bone mechanical properties, and imbalance of oxidation-antioxidant levels in rats. "	( [EXPERIMENTAL STUDY ON EFFECT OF NICOTINE INTAKE ON IMPACT OF BONE MICROSTRUCTURE AND OXIDATIVE STRESS IN RATS]. Chen, Y; Ma, J; Ma, X; Wang, Y; Xing, D; Yang, Y; Zhu, S, 2016)	2.16
"The nicotine-induced increase in AUC of facial stimulation-evoked N1 was dose-dependent with a 50% effective concentration (EC"	( Nicotine modulates the facial stimulation-evoked responses in cerebellar granule cell layer in vivo in mice. Bing, YH; Chu, CP; Cui, SB; Li, YZ; Qiu, DL; Su, WH; Wu, MC; Xu, YH; Zhang, BB, 2019)	2.44
"Nicotine and cotinine enhance alcoholic fatty liver in wild type (WT) mice but not in CYP2A5 knockout (KO) mice, and reactive oxygen species (ROS) generated during the CYP2A5-mediated metabolism contributes to the enhancing effect."	( Suppressed hepatocyte proliferation via a ROS-HNE-P21 pathway is associated with nicotine- and cotinine-enhanced alcoholic fatty liver in mice. Cederbaum, AI; Chen, X; Lu, Y; Wang, K, 2019)	1.46
"Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. "	( Nicotine Self-Administration With Tobacco Flavor Additives in Male Rats. Bradley, CA; Odineal, EM; Palmatier, MI; Sheppard, AB; Smith, AL; Williams, EA, 2020)	3.44
"Nicotine promotes proliferation of NSCLC cells through regulating the miR-218/CDK6 axis, which may be a potential therapeutic target for lung cancer."	( Downregulation of miR-218 by nicotine promotes cell proliferation through targeting CDK6 in non-small cell lung cancer. Dong, K; Guan, JZ; Han, X; Liu, Z; Lu, C; Wang, C; Wang, Z; Zhao, G, 2019)	2.25
"Nicotine promotes smoking partly by binding to β2-containing nicotinic acetylcholine receptors (β2*-nAChRs) in the brain. "	( Effect of a nicotine vaccine on nicotine binding to β2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers. Bois, F; Cosgrove, KP; D'Souza, DC; Esterlis, I; Hannestad, JO; Hatsukami, DM; O'Malley, SS; Perkins, E; Seibyl, JP; Tyndale, RF, 2013)	2.21
"Nicotine did not increase mean plasma concentration significantly during fasting or with enteral nutrition, although the extent of levodopa absorption was reduced by 34% to 60% in some individuals and the mean plasma concentration of levodopa was statistically decreased by nicotine in subjects who received enteral nutrition. "	( Effect of nicotine on the pharmacokinetics of levodopa. Iwaki, H; Kaneta, M; Kubo, M; Kyaw, WT; Nagai, M; Nishikawa, N; Nomoto, M; Tsujii, T, )	1.98
"Nicotine promotes physical addiction to tobacco as well as causes pulmonary diseases, cardiovascular diseases or cancers to smokers."	( [Compounds in tobacco smoke and pathogenesis of the diseases]. Sasaki, J, 2013)	1.11
"Nicotine plays an important role in the initiation and maintenance of tobacco smoking. "	( The "stop" and "go" of nicotine dependence: role of GABA and glutamate. D'Souza, MS; Markou, A, 2013)	2.14
"Both nicotine and alcohol activate the mesocorticolimbic dopamine system, producing downstream dopamine signals that promote the drug reinforcement process."	( Potential substrates for nicotine and alcohol interactions: a focus on the mesocorticolimbic dopamine system. Dani, JA; Dong, Y; Doyon, WM; Ostroumov, A; Thomas, AM, 2013)	1.15
"Nicotine vaccine can generate specific antibodies that can sequester nicotine from cigarette smoke in the blood, and prevent its access to the brain and minimize positive reinforcing effects, which may help smokers to stop smoking."	( [Recent progress in vaccines against nicotine addiction]. Wang, GB; Zhu, CJ, 2013)	1.38
"Nicotine was able to enhance the in vivo overflow of the three amino acids being more potent in stimulating GLU overflow."	( Inhibitory effects of beta-amyloid on the nicotinic receptors which stimulate glutamate release in rat hippocampus: the glial contribution. Govoni, S; Grilli, M; Marchi, M; Mura, E; Olivero, G; Preda, S; Salamone, A; Zappettini, S, 2014)	1.12
"Nicotine is known to lower background craving and negative affect, but the difference between patch and placebo appeared to dissipate in the hours immediately preceding lapse episodes."	( Effect of high-dose nicotine patch on craving and negative affect leading up to lapse episodes. Ferguson, SG; Shiffman, S, 2014)	1.45
"Nicotine is able to activate mitogenic signalling pathways, which promote cell growth or survival as well as increase chemoresistance of cancer cells. "	( Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability. Chen, C; Dai, W; He, H; Luo, LY; Mariyannis, A; Nishioka, T; Shen, L, 2014)	3.29
"Nicotine did not inhibit or stimulate alkaline phosphatase (ALP) activity or the amount of osteocalcin in C2C12 cells in the presence of rhBMP-2 in vitro."	( The effect of nicotine on osteoinduction by recombinant human bone morphogenetic protein 2. Bessho, K; Hussain, A; Kaihara, S; Takahashi, K; Tamura, K; Togo, Y, 2014)	1.48
"The nicotine-induced increase in sIPSC frequency was independent on voltage-gated calcium channels and dependent on Ca(2+)-induced Ca(2+) release (CICR)."	( Nicotine increases GABAergic input on rat dorsal raphe serotonergic neurons through alpha7 nicotinic acetylcholine receptor. Chavarría, K; Garduño, J; Hernández-López, S; Hernández-Vázquez, F; Mihailescu, SP, 2014)	2.33
"Does nicotine suppress alcohol-induced aversive effects via the BF? We hypothesized that nicotine may act via the BF to suppress sleep-promoting effects of alcohol."	( Nicotine administration in the wake-promoting basal forebrain attenuates sleep-promoting effects of alcohol. Lodhi, S; Sahota, P; Sharma, R; Thakkar, MM, 2015)	2.31
"Nicotine can activate dopaminergic neurons within the ventral tegmental area (VTA). "	( Effect of Transient Inactivation of Ventral Tegmental Area on the Expression and Acquisition of Nicotine-Induced Conditioned Place Preference in Rats. Ali Beig, H; Bourbour, Z; Chalabi-Yani, D; Hosseini, SB; Meftahi, GH; Ranjabaran, M; Sadeghi-Gharajehdaghi, S; Sahraei, H, 2015)	2.08
"Nicotine promotes rooting in leaf explants of tomato (Lycopersicon esculentum Miller var. "	( Nicotine promotes rooting in leaf explants of in vitro raised seedlings of tomato, Lycopersicon esculentum Miller var. Pusa Ruby. Bamel, K; Gupta, R; Gupta, SC, 2015)	3.3
"Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension."	( Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats. Bergamaschi, CT; Boim, MA; Campos, RR; Ferreira, VM; Maquigussa, E; Passos, CS; Pontes, RB, 2016)	1.59
"Nicotine induced an increase in the spike firing rate of PVN CRH-mRNA-expressing neurons in a concentration-dependent manner."	( Nicotine excites corticotropin-releasing hormone mRNA-expressing neuron in the hypothalamic paraventricular nucleus in vitro in rats. Chu, CP; Cui, BR; Cui, X; Qiu, DL; Zhang, BB, 2016)	2.6
"Nicotine may also increase cognitive control among nonsmokers, and this may vary as a function of trait cognitive control."	( Nicotine-induced cortical activation among nonsmokers with moderation by trait cognitive control. Drobes, DJ; Evans, DE; Jentink, KG; Sutton, SK; Van Rensburg, KJ, 2016)	2.6
"Nicotine tended to increase myocardial blood flow in the circumflex artery territory, but this effect failed to reach the level of statistical significance (from 0.56+/-0.06 to 0.63+/-0.03 ml/min/g; p>.15)."	( Nicotine does not compromise resting myocardial blood flow autoregulation in smokers at high cardiovascular risk. Argacha, JF; Garcia, C; Goldman, S; Gujic, M; Preumont, N; van de Borne, P; Van Simaeys, G; Xhaët, O, 2008)	2.51
"Nicotine may enhance the reinforcing value of other reinforcers. "	( The generality of nicotine as a reinforcer enhancer in rats: effects on responding maintained by primary and conditioned reinforcers and resistance to extinction. Dallery, J; Raiff, BR, 2008)	2.12
"Nicotine displays rewarding and aversive effects, and while dopamine has been linked with nicotine's reward, the neurotransmitter(s) involved with aversion remains speculative. "	( Acute nicotine changes dynorphin and prodynorphin mRNA in the striatum. Hadjiconstantinou, M; Isola, R; Neff, NH; Tejwani, GA; Zhang, H, 2009)	2.28
"Nicotine did not increase DAT function and cell surface expression in striatum, indicating that nicotine modulates DAT function in a brain region-specific manner."	( Nicotinic receptor activation increases [3H]dopamine uptake and cell surface expression of dopamine transporters in rat prefrontal cortex. Apparsundaram, S; Dwoskin, LP; Zhu, J, 2009)	1.07
"Nicotine was able to produce this phenotype in embryos lacking supraspinal input."	( Acute nicotine exposure and modulation of a spinal motor circuit in embryonic zebrafish. Galvez, F; Svoboda, KR; Thomas, LT; Welsh, L, 2009)	1.56
"Nicotine did not enhance striatal markers when administered to monkeys with pre-existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning."	( Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys. Bordia, T; Huang, LZ; Michael McIntosh, J; Parameswaran, N; Quik, M, 2009)	2.52
"Nicotine may increase intracellular free Ca(2+) concentrations via the influx of extracellular Ca(2+)+ mainly across L-type voltage-gated Ca(2+) channels, in a manner related to the alpha4beta2 subtype of nicotinic receptors."	( An increase in intracelluar free calcium ions modulated by cholinergic receptors in rat facial nucleus. Li, N; Sun, DW; Zhang, QG; Zhou, R; Zhu, FG, 2009)	1.07
"Nicotine was found to increase the expression of interleukin-1, interleukin-8 and RANKL mRNA and protein in U2OS cells (p < 0.05). "	( Up-regulation of osteolytic mediators in human osteosarcoma cells stimulated with nicotine. Chang, YC; Ho, YC; Huang, FM; Yang, SF, 2009)	2.02
"Nicotine plays a role in smoking-associated cardiovascular diseases, and may upregulate matrix metalloproteinase (MMP)-2 and MMP-9. "	( Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine. Cau, SB; Gerlach, RF; Izidoro-Toledo, TC; Jacob-Ferreira, AL; Martinez, ML; Moreno, H; Palei, AC; Tanus-Santos, JE, 2010)	2.02
"Nicotine did not produce statistically significant long-lasting effects on NGF levels in the cerebral cortex, or in the BF."	( Nicotine increases the expression of neurotrophin receptor tyrosine kinase receptor A in basal forebrain cholinergic neurons. Cantù, C; Chiamulera, C; Dalfini, AC; Decimo, I; Di Chio, M; Fazzini, F; Fiorini, Z; Formaggio, E; Fumagalli, G, 2010)	2.52
"Nicotine plays an important role in cigarette-smoke-associated airway disease. "	( Nicotine enhances murine airway contractile responses to kinin receptor agonists via activation of JNK- and PDE4-related intracellular pathways. Cardell, LO; Xu, Y; Zhang, Y, 2010)	3.25
"Nicotine was found to inhibit cardiomyocyte viability in a concentration-dependent manner. "	( Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression. Kong, X; Sheng, Y; Yang, R; Zhou, X, 2010)	3.25
"Nicotine promotes cardiomyocyte apoptosis by inducing oxidative stress and disrupting apoptosis-related gene expression."	( Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression. Kong, X; Sheng, Y; Yang, R; Zhou, X, 2010)	3.25
"The nicotine-induced increase in glutamatic acid decarboxylase (GAD) and GABA(A) receptor mRNA resulted in increased GABA-induced currents and increased expression of mucin."	( Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium. Fu, XW; Spindel, ER; Wood, K, 2011)	1.27
"This nicotine-induced increase in lipid peroxidation was prevented by both vitamin E and HRe-1."	( Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver. Akar, S; Akcay, F; Aktas, O; Dane, S; Demircan, B; Gul, M; Gumustekin, K; Oztasan, N; Suleyman, H; Taysi, S, 2010)	1.1
"Nicotine did not enhance the reinforcing properties of the visual cue paired with drug delivery. "	( Patterns of responding differentiate intravenous nicotine self-administration from responding for a visual stimulus in C57BL/6J mice. Contet, C; Jarrell, H; Kenny, PJ; Markou, A; Whisler, KN, 2010)	2.06
"Nicotine promotes glutamatergic synaptic plasticity in dopaminergic (DA) neurons in the ventral tegmental area (VTA), which is thought to be an important mechanism underlying nicotine reward. "	( Exposure of nicotine to ventral tegmental area slices induces glutamatergic synaptic plasticity on dopamine neurons. Jin, Y; Wang, H; Wu, J; Yang, K, 2011)	2.19
"Nicotine did not cause an excessive expression of TNF-α, IL-8, and IL-6, nor did it affect protein production from the MUC5AC gene."	( Nicotine suppresses inflammatory factors in HBE16 airway epithelial cells after exposure to cigarette smoke extract and lipopolysaccharide. Kolosov, VP; Li, Q; Perelman, JM; Zhou, X, 2010)	2.52
"As nicotine is known to activate protein kinase C (PKC) signaling, the authors also hypothesized that in AIFs, nicotine-induced up-regulation of Wnt signaling might be due to PKC activation."	( Mechanism for nicotine-induced up-regulation of Wnt signaling in human alveolar interstitial fibroblasts. Cerny, LM; Rehan, VK; Sakurai, R; Torday, JS, 2011)	1.24
"Nicotine appears to enhance certain forms of cognition in nonsmokers, but its specificity to subtypes of cognition is not known."	( Effects of nicotine on attention and inhibitory control in healthy nonsmokers. de Wit, H; Wignall, ND, 2011)	1.48
"Nicotine-induced increase of presynaptic glutamate release also contributed to the induction of synaptic plasticity, likely through increased activation of NMDAR."	( Nicotine potentiation of excitatory inputs to ventral tegmental area dopamine neurons. Gallagher, K; Mao, D; McGehee, DS, 2011)	2.53
"Nicotine did not enhance responding for an audiovisual stimulus relative to baseline at any dose when administered before repeated daily administration, but responding was enhanced at 0.1, 0.3, and 1.0 mg/kg of nicotine after daily administration."	( The effects of repeated exposure on the reward-enhancing effects of nicotine. Barrett, ST; Odum, AL, 2011)	1.33
"Nicotine can enhance various indices of cognitive performance, including working memory span capacity measured using the odor span task (OST)."	( Nicotine improves working memory span capacity in rats following sub-chronic ketamine exposure. Rushforth, SL; Shoaib, M; Steckler, T, 2011)	2.53
"A nicotine-induced increase or decrease in apoptosis as assessed by the TUNEL assay in BEAS-2B could not be detected."	( Analysis of nicotine-induced DNA damage in cells of the human respiratory tract. Friehs, G; Ginzkey, C; Hackenberg, S; Hagen, R; Kleinsasser, NH; Koehler, C; Richter, E; Stueber, T, 2012)	1.32
"The nicotine-induced increase in SCS level was suppressed by DHβE, but not MLA."	( 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)	0.85
"Nicotine can cause oxidative damage to organisms; however, some bacteria, for example Pseudomonas sp. "	( Unraveling the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress by ¹H NMR-based metabolomics. Lu, Z; Wang, X; Yan, X; Ye, Y; Zhang, L, 2012)	2.05
"Nicotine could inhibit HDAC6 activity and chaperone-dependent activation of GR. "	( Nicotine inhibits histone deacetylase 6 activity and chaperone-dependent activation of the glucocorticoid receptor in A549 cells. Li, W; Lin, JT; Sun, LC; Zhang, L; Zhang, XY; Zhou, TL, 2012)	3.26
"Nicotine is known to generate oxidative stress through cytochrome P450 2A6 (CYP2A6)-mediated metabolism in the liver and other organs, including macrophages. "	( An LC-MS/MS method for concurrent determination of nicotine metabolites and the role of CYP2A6 in nicotine metabolite-mediated oxidative stress in SVGA astrocytes. Ande, A; Earla, R; Jin, M; Kumar, A; Kumar, S; Mitra, AK; Silverstein, PS, 2012)	2.07
"Nicotine induced an increase in cell proliferation and a decrease of apoptosis in Caco-2 and HCT-8 cells. "	( Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways. Bizzarri, M; Coluccia, P; Cucina, A; D'Anselmi, F; Dinicola, S; Pasqualato, A; Proietti, S, 2012)	3.26
"Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABA(A)R antagonist picrotoxin. "	( Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo. Buch, S; Gott, KM; Gundavarapu, S; Harrod, KS; Jaramillo, RJ; Langley, RJ; McIntosh, JM; Mishra, NC; Peña-Philippides, JC; Rir-Sima-Ah, J; Saeed, AI; Singh, SP; Sopori, ML; Wilder, JA, 2012)	1.82
"Nicotine seems to increase the occurrence of nausea and vomiting."	( [A possible analgesic effect of nicotine on postoperative pain]. Pachai, A; Petersen, RH; Vibe Nielsen, S, 2012)	1.38
"Nicotine is known to enhance long-term hippocampus dependent learning and memory in both rodents and humans via its activity at nicotinic acetylcholinergic receptors (nAChRs). "	( Learning and nicotine interact to increase CREB phosphorylation at the jnk1 promoter in the hippocampus. Adoff, MD; Gould, TJ; Kenney, JW; Logue, SF; Poole, RL, 2012)	2.19
"Nicotine promotes endothelial cell migration, proliferation, survival, tube formation and nitric oxide (NO) production in vitro, mimicking the effect of other angiogenic growth factors."	( Nicotine and pathological angiogenesis. Cooke, JP; Lee, J, 2012)	2.54
"Nicotine did not produce an anxiolytic effect in male HINT1 -/- mice, but rather an anxiogenic response."	( Acute behavioral effects of nicotine in male and female HINT1 knockout mice. Barbier, E; Chen, X; Damaj, MI; Jackson, KJ; Wang, JB, 2012)	1.39
"Nicotine-induced increase of glutamatergic EPSC frequency persisted 10-20 min after drug withdrawal."	( Presynaptic α4β2 nicotinic acetylcholine receptors increase glutamate release and serotonin neuron excitability in the dorsal raphe nucleus. Galarraga, E; Galindo-Charles, L; Garduño, J; Hernandez-Lopez, S; Jiménez-Rodríguez, J; Mihailescu, S; Tapia, D, 2012)	1.1
"Nicotine is known to enhance aspects of cognitive functioning in abstinent smokers, but the effects on specific areas of executive functions and in non-smokers are inconclusive. "	( Investigating the impact of nicotine on executive functions using a novel virtual reality assessment. Dawkins, L; Edginton, T; Froggatt, D; Jansari, AS, 2013)	2.13
"Nicotine-induced increase in erythrocyte MDA level was prevented by both HRe-1 and vitamin E."	( Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E. Akar, S; Akcay, F; Aktas, O; Altinkaynak, K; Dane, S; Gul, M; Gumustekin, K; Keles, S; Oztasan, N; Suleyman, H; Taysi, S; Timur, H, 2002)	1.29
"Nicotine did not inhibit apoptosis induced by angiotensin II (100 nM, 24 h)."	( Nicotine inhibits cardiac apoptosis induced by lipopolysaccharide in rats. Bayna, E; Dalle Molle, E; Lew, WY; Suzuki, J, 2003)	2.48
"Nicotine can enhance attentional performance in humans, a property that may be of therapeutic utility."	( Involvement of the prefrontal cortex but not the dorsal hippocampus in the attention-enhancing effects of nicotine in rats. Hahn, B; Shoaib, M; Stolerman, IP, 2003)	1.98
"Nicotine may enhance LH-based cognitive performance by increasing LH cognitive resources or by reducing the influence of RVF distracting stimuli."	( Effects of transdermal nicotine on lateralized identification and memory interference. Gilbert, DG; McClernon, FJ; Radtke, R, 2003)	1.35
"Nicotine did enhance contextual fear conditioning in the groups that received nicotine for both training and testing."	( Nicotine produces a within-subject enhancement of contextual fear conditioning in C57BL/6 mice independent of sex. Gould, TJ, )	2.3
"Nicotine may thus enhance the contrast of dopamine signals associated with behavioral cues."	( Frequency-dependent modulation of dopamine release by nicotine. Sulzer, D; Zhang, H, 2004)	1.29
"Nicotine can enhance contextual learning while ethanol impairs some forms of learning. "	( Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning. Balogh, SA; Beaudet, A; Booker, TK; Heinemann, SF; Keller, AB; Keller, JJ; Paylor, R; Picciotto, MR; Wehner, JM, 2004)	2.01
"The nicotine-induced increase in the size of the readily releasable pool was blocked by alphaBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through alpha7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals."	( Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles. Turner, TJ, 2004)	2.25
"This nicotine-induced increase in blood-brain barrier permeability was significantly attenuated by both the blood-brain barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 +/- 0.2 and 0.3 +/- 0.2 microl.g(-1).min(-1), respectively."	( Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors. Davis, TP; Egleton, RD; Hawkins, BT, 2005)	0.78
"Nicotine exposure promotes hippocampal gamma oscillations in a methyllycaconitine-sensitive manner."	( Role of alpha7-nicotinic acetylcholine receptors in tetanic stimulation-induced gamma oscillations in rat hippocampal slices. Ellsworth, K; Javedan, SP; Kimura, R; Lukas, RJ; Marxer-Miller, S; Murray, TA; Song, C; Wakui, M; Wu, J, 2005)	1.05
"Nicotine appears to activate specific intracellular death-related pathways, probably by bax-dependent activation of caspase-3, inducing apoptosis in Leydig cells. "	( Nicotine induces apoptosis in TM3 mouse Leydig cells. Jang, MH; Joo, KJ; Kim, CJ; Kim, KH; Kwon, CH; Park, HJ, 2005)	3.21
"The nicotine-induced increase in 86Rb+ efflux was significantly greater in NDZ as compared to DZ in the "thalamus." There was no statistically significant difference in the effects of nicotine in the frontal cortex, hippocampus, and striatum of these two groups. "	( Evidence of cellular nicotinic receptor desensitization in rats exhibiting nicotine-induced acute tolerance. Gross, DF; James, JR; Lapp, LN; Philibin, SD; Robinson, SE; Rosecrans, JA; Vann, RE, 2006)	1.12
"Nicotine could suppress this timing-dependent mechanism by desensitizing nAChRs."	( Nicotine-induced switch in the nicotinic cholinergic mechanisms of facilitation of long-term potentiation induction. Hamaue, N; Jia, Y; Sumikawa, K; Yamazaki, Y, 2005)	2.49
"Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC."	( A randomized trial of nicotine enemas for active ulcerative colitis. Courtney, E; Evans, BK; Green, JT; Hawkes, ND; Ingram, JR; Newcombe, RG; Pillai, S; Rhodes, J; Srivastava, ED; Swift, JL; Thomas, GA; Williams, GT, 2005)	1.36
"Nicotine tended to enhance performance at the long-delay stage specifically but only against a background of relatively low baseline performance."	( Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeys. Ballard, T; Feldon, J; Higgins, GA; Pryce, CR; Spinelli, S, 2006)	1.37
"Nicotine induced increase in cardiac interval was not altered by pirenzepine."	( Muscarinic type 1 receptors mediate part of nitric oxide's vagal facilitatory effect in the isolated innervated rat right atrium. Hogan, K; Markos, F, 2007)	1.06
"Nicotine is thought to inhibit the production of proinflammatory cytokines from macrophages through an anti-inflammatory pathway that is dependent on nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR). "	( Effect of nicotine on IL-18-initiated immune response in human monocytes. Hamano, R; Iwagaki, H; Nishibori, M; Takahashi, HK; Tanaka, N; Yoshino, T, 2006)	2.18
"Nicotine promotes angiogenesis via stimulation of nAChR-dependent endothelial cell migration. "	( A central role for nicotinic cholinergic regulation of growth factor-induced endothelial cell migration. Chang, E; Cooke, JP; Ishii-Watabe, A; Katzenberg-Clark, R; Ng, MK; Wang, BY; Wu, J, 2007)	1.78
"Nicotine did not cause any alteration on a single dose of carbachol (3 x 10(-5) M) and sodium nitroprusside (10(-5) M) induced relaxation responses."	( Nicotine potentiates the nitrergic relaxation responses of rabbit corpus cavernosum tissue via nicotinic acetylcholine receptors. Bozkurt, NB; Pekiner, C; Sarioglu, Y; Vural, IM, 2007)	2.5
"Nicotine is known to inhibit the production of pro-inflammatory cytokines from macrophages through the stimulation of nicotinic acetylcholine receptor alpha7 subunit."	( The immunosuppressive effects of nicotine during human mixed lymphocyte reaction. Hamano, R; Iwagaki, H; Kanke, T; Liu, K; Nishibori, M; Sadamori, H; Takahashi, HK; Tanaka, N; Yagi, T; Yoshino, T, 2007)	1.34
"Nicotine led to the increase in the amplitudes of the EFS-evoked contractile responses in a dose-dependent manner."	( Nicotine potentiates the electrical field stimulation-evoked contraction of non-pregnant rabbit myometrium. Barun, S; Ercan, ZS; Nas, T; Oztürk, GS; Sarioğlu, Y; Vural, IM, 2007)	2.5
"Nicotine promotes induction of long-term potentiation (LTP) in the SC path; however, it is not known whether the modulatory effect of nicotine on LTP induction is pathway-specific."	( Nicotine gates long-term potentiation in the hippocampal CA1 region via the activation of alpha2* nicotinic ACh receptors. Boulter, J; Brennan, RJ; Nakauchi, S; Sumikawa, K, 2007)	2.5
"Nicotine appears to enhance attention, while nicotine withdrawal leads to attentional deficits in humans that are ameliorated with nicotine administration. "	( Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats. Markou, A; Semenova, S; Stolerman, IP, )	2.01
"Nicotine promotes CAM expression on HCAECs, shifting them toward a proatherosclerotic state. "	( HMG-CoA reductase inhibitors reduce nicotine-induced expression of cellular adhesion molecules in cultured human coronary endothelial cells. Angri, V; Calabrò, P; Chiariello, M; Cirillo, P; De Rosa, S; Fiorentino, I; Gargiulo, A; Musto D'Amore, S; Pacileo, M; Petrillo, G; Prevete, N; Sasso, L; Ucci, G, 2007)	2.06
"(2) Nicotine vaccines produce antibodies that bind nicotine, the chief addictive agent in cigarettes, and prevent it from entering the brain."	( Nicotine vaccines for smoking cessation. Foerster, V; Murtagh, J, 2007)	2.26
"Nicotine is known to enhance learning and memory in hippocampus-dependent tasks such as contextual fear conditioning. "	( Hippocampal alpha4beta2 nicotinic acetylcholine receptor involvement in the enhancing effect of acute nicotine on contextual fear conditioning. Davis, JA; Gould, TJ; Kenney, JW, 2007)	2
"Nicotine can both activate and desensitize/inactivate nicotinic acetylcholine receptors (nAChRs). "	( It is not "either/or": activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Addy, NA; Brunzell, DH; Mineur, YS; Picciotto, MR, 2008)	1.99
"Nicotine tended to enhance eye-gaze orientation to emotional pictures versus neutral pictures in women, but it had no significant effect on eye-gaze in men."	( Emotional stimuli and context moderate effects of nicotine on specific but not global affects. Dillon, A; Gilbert, DG; Huber, J; Rabinovich, NE; Riise, H; Sugai, C, 2008)	1.32
"Nicotine can increase size and severity of experimental choroidal neovascularization (CNV); however, the mechanism is uncertain. "	( Nicotine promotes contribution of bone marrow-derived cells to experimental choroidal neovascularization in mice. Hou, HY; Wang, BR; Wang, YS; Xu, JF, 2008)	3.23
"Nicotine appears to cause relaxation by releasing a nonadrenergic inhibitory substance since 1) alpha and beta adrenergic antagonists are ineffective against nicotine and 2) nicotine retains activity on preparations from reserpinized animals."	( Nicotine action on rat colon. Romano, C, 1981)	2.43
"Nicotine reduced the increase in irritability, anxiety, difficulty concentrating, restlessness, impatience, and somatic complaints that subjects reported after cessation."	( Effect of nicotine on the tobacco withdrawal syndrome. Hatsukami, DK; Hughes, JR; Krahn, D; Luknic, A; Malin, S; Pickens, RW, 1984)	1.39
"Nicotine was found to produce an increase of 3H-NA uptake and endogenous NA in the cerebral cortex and pons-medulla, which was most pronounced at the age of one week."	( Effects of neonatal nicotine administration on the postnatal development of central noradrenaline neurons. Hallman, H; Jonsson, G, 1980)	1.31
"Nicotine failed to inhibit the hypotensive effect of eledoisine, prostacyclin, isoprenaline and papaverine."	( Inhibition by nicotine of the vasodilator effect of bradykinin: evidence for a prostacyclin-dependent mechanism. Ercan, ZS; Ersoy, A; Türker, RK; Zengil, H, 1982)	1.35
"d-Nicotine did not inhibit the responses of the artery to electrical transmural stimulation."	( The effects of d-nicotine and l-isomer on nicotinic receptors. Fujiwara, M; Ikushima, S; Muramatsu, I; Sakakibara, Y; Yokotani, K, 1982)	1.16
"This nicotine-induced increase was blocked by treatment with hexamethonium 50 microgram/animal given intraventricularly or atropine 100 microgram/kg given intravenously."	( Central effect of nicotine on gastric acid secretion in rats. Fujiwara, M; Ishikawa, T; Nagasaka, Y; Osumi, Y, 1980)	1.05
"(-)-Nicotine was shown to produce in vivo protection against neurobehavioral effects caused by systemically administered kainic acid (KA), an excitotoxin that has been widely used to induce temporal lobe convulsions including "wet dog shakes" in experimental animals. "	( (-)-nicotine protects against systemic kainic acid-induced excitotoxic effects. Borlongan, CV; Cahill, DW; Freeman, TB; Ross, SD; Sanberg, PR; Shimizu, T; Shytle, RD, 1995)	1.41
"The nicotine-induced increase in [Ca]in was inhibited not only by nicotinic antagonists but also by muscarinic antagonists, while the muscarine-induced [Ca]in increase was little affected by nicotinic antagonists."	( Pharmacology of nicotine-induced increase in cytosolic Ca2+ concentrations in chick embryo ciliary ganglion cells. Sorimachi, M, 1995)	1.12
"2. d-Nicotine did not produce any responses except for the case of guinea-pig trachea."	( Inhibitory effects of d-nicotine on the responses evoked by 1-isomer in trachea and bronchus isolated from guinea-pig and rabbit. Funayama, N; Shinkai, M; Takayanagi, I, 1995)	1.05
"Nicotine abuse may cause severe nephrourologic diseases such as nephrosclerosis, hypertension and tumour of the bladder. "	( [Adverse effects of smoking from the nephrologic viewpoint]. Kopsa, H, 1994)	1.73
"Nicotine caused an increase in respiratory rate and this effect was abolished by prazosin."	( Effects of adrenoceptor blockers on the cardiorespiratory response to nicotine in rats. Fasanmade, AA; Oyebola, DD, 1993)	1.24
"Nicotine is thought to activate the nigrostriatal dopaminergic pathway and increase the release of dopamine in the striatum, and this can explain the effects of smoking in these patients."	( Effects of smoking in patients with early-onset Parkinson's disease. Ishikawa, A; Miyatake, T, 1993)	1.01
"Nicotine replacements produce lower nicotine concentrations than cigarettes, and no tar and carbon monoxide; thus, it is difficult to justify absolute contraindications to these products."	( Risk-benefit assessment of nicotine preparations in smoking cessation. Hughes, JR, 1993)	1.3
"Nicotine and capsaicin produce many similar physiological responses that include pain, irritation, and vasodilation. "	( Capsaicin and nicotine both activate a subset of rat trigeminal ganglion neurons. Liu, L; Simon, SA, 1996)	2.1
"Nicotine was found to produce significant dose-related increases in leukocyte rolling and adhesion."	( Nicotine induces leukocyte rolling and adhesion in the cerebral microcirculation of the mouse. Linthicum, DS; Yong, T; Zheng, MQ, 1997)	2.46
"The nicotine-induced increase in the cyclic GMP content in cerebral arteries was depressed by KN62."	( Effect of Ca2+/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation. Ayajiki, K; Okamura, T; Toda, N, 1997)	0.78
"Nicotine patches produce only minor disturbances of autonomic regulation."	( Autonomic effects of nicotine patch administration in habitual cigarette smokers: a double-blind, placebo-controlled study using spectral analysis of RR interval and systolic arterial pressure variabilities. Bertocchi, F; Lucini, D; Malliani, A; Pagani, M, 1998)	1.34
"(-)Nicotine did not blunt the AbetaP activation of phospholipase C."	( (-)Nicotine inhibits the activations of phospholipases A2 and D by amyloid beta peptide. Kanfer, JN; Singh, IN; Sitar, DS; Sorrentino, G, 1998)	1.44
"Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity."	( Nicotine-induced perturbations on heart rate, body temperature and locomotor activity daily rhythms in rats. Bruguerolle, B; Gantenbein, M; Pelissier, AL, 1998)	2.46
"The nicotine-induced increase of receptors in cerebral cortical cultures was not blocked by either mecamylamine or dihydro-beta-erythroidine."	( Nicotinic receptor binding sites in rat primary neuronal cells in culture: characterization and their regulation by chronic nicotine. Dávila-García, MI; Houghtling, RA; Kellar, KJ; Qasba, SS, 1999)	0.99
"Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%."	( Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm. Amit, Z; Gaskin, S; Horan, JT; Smith, BR, 1999)	1.4
"Nicotine may be the cause of this protective effect."	( Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results. Sandborn, WJ, 1999)	2.47
"Nicotine was found to increase swim speed in a Morris water maze paradigm with a hidden platform; however, no beneficial effects of nicotine in reference memory were obtained for either age group."	( The effects of nicotine on learning and memory: a neuropsychological assessment in young and senescent Fischer 344 rats. Attaway, CM; Compton, DM; Turner, MD, 1999)	1.38
"Nicotine is known to enhance cognitive function but the mechanism is unknown. "	( Nicotine reverses GABAergic inhibition of long-term potentiation induction in the hippocampal CA1 region. Fujii, S; Jia, Y; Sumikawa, K; Yang, A, 2000)	3.19
"Nicotine failed to activate mouse plantar sweat glands at any of the concentrations used (from 3 x 10(-6) to 3 x 10(-1) M)."	( Evaluation of direct and axon reflex sweating in the mouse. Navarro, X; Vilches, JJ, 2000)	1.03
"Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R."	( Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF. Mathur, RS; Mathur, SP; Young, RC, 2000)	1.27
"The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects."	( Mechanism for increase in expression of cerebral diazepam binding inhibitor mRNA by nicotine: involvement of L-type voltage-dependent calcium channels. Higo, A; Katsura, M; Mohri, Y; Ohkuma, S; Shuto, K; Takesue, M; Tarumi, C; Tsujimura, A, 2000)	1.01
"The nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of nicotine, suggesting that the intrinsic activity of nicotine was greater in the FSL than in the FRL rats."	( Expression and function of striatal nAChRs differ in the flinders sensitive (FSL) and resistant (FRL) rat lines. Auta, J; Costa, E; Guidotti, A; Javaid, JI; Lecca, D; Nelson, M; Overstreet, DH, 2000)	0.79
"Nicotine can enhance performance in several tests of cognition but the specific nicotinic receptor subtypes mediating these effects are largely unknown. "	( Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain. Caldarone, BJ; Duman, CH; Picciotto, MR, 2000)	1.75
"1. Nicotine can activate primary afferent nociceptors, one result of which is to increase neurogenic plasma extravasation. "	( Endogenous opioids suppress activation of nociceptors by sub-nanomolar nicotine. Benowitz, NL; Levine, JD; Miao, FJ, 2001)	1.17
"This nicotine-induced increase in cell proliferation was inhibited in a dose-dependent manner by the addition of D-tubocurarine."	( Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture. El Haj, AJ; Magnay, JL; Preston, MR; Thomas, PB; Walker, LM, 2001)	0.77
"Nicotine might inhibit the uptake of dopamine through the nAChR, which could serve as a preventive factor against neurodegenerative diseases."	( Nicotinic acetylcholine receptors and neurodegenerative disease. Kawakami, H; Nakamura, S; Takahashi, T; Yamashita, H, 2001)	1.03
"The nicotine-induced increase in mpps and action potentials were inhibited during simultaneous application of domperidone; L-glutamic acid diethyl ester hydrochloride, a non-selective glutamate receptor antagonist; and/or dihydro-beta-erythroidine, a central nicotinic acetylcholine receptor (alpha4beta2 type) antagonist."	( Excitation of rat striatal large neurons by dopamine and/or glutamate released from nerve terminals via presynaptic nicotinic receptor (A4beta2 type) stimulation. Amano, H; Amano, T; Matsubayashi, H; Sasa, M, 2001)	0.79
"Nicotine at a lower concentration of 0.01 micromol/L had no effect on endothelial cell surface intercellular adhesion molecule expression compared with controls (P =.614). "	( Effects of nicotine on intercellular adhesion molecule expression in endothelial cells and integrin expression in neutrophils in vitro. Gu, Y; Lucas, MJ; Speer, P; Wang, Y; Zhang, Y, 2002)	2.15
"The nicotine-induced increase in the cortical CBF was significantly attenuated by propranolol (10 mg/kg, i.v.) and ICI 118,551 (a beta2-adrenoceptor antagonist, 10 mg/kg, i.v.) but not by metoprolol (a beta1-adrenoceptor antagonist, 10 mg/kg, i.v.)."	( Nicotine-induced NO-mediated increase in cortical cerebral blood flow is blocked by beta2-adrenoceptor antagonists in the anesthetized rats. Kawashima, K; Lee, TJ; Uchida, S, 2002)	2.24
"The nicotine-mediated increase was shown to occur at least in part through increase of the activity of dopamine neurons in the ventral tegmental area."	( Receptors in the ventral tegmental area mediating nicotine-induced dopamine release in the nucleus accumbens. Hashim, A; Lajtha, A; Sershen, H; Sziráki, I, 2002)	1.05
"Nicotine dependency plays a minor role in determining the smoking habits of those who continue to smoke on a long-term basis."	( Changes in the cigarette consumption of smokers in relation to changes in tar/nicotine content of cigarettes smoked. Garfinkel, L, 1979)	1.21
"3. Nicotine was found to increase vasopressin secretion by all three routes of administration."	( The release of vasopressin by nicotine: further studies on its site of action. Castro de Souza, E; Rocha E Silva, M, 1977)	1.06
"Thus nicotine does not inhibit the addition of the two extra isoprene units plus two hydroxyl groups (at C1 and C1') to a C40 carotenoid skeleton."	( Effect of nicotine on biosynthesis of C50 carotenoids in Halobacterium cutirubrum. Kates, M; Kushwaha, SC, 1976)	1.11
"Nicotine patches produce end-of-treatment smoking cessation rates that range from 18% to 77%; these rates are about twice those of placebo-treated subjects. "	( Tobacco dependence and the nicotine patch. Clinical guidelines for effective use. Baker, TB; Fiore, MC; Jorenby, DE; Kenford, SL, 1992)	2.02
"Nicotine was found to increase the levels of proenkephalin mRNA in the adrenal medulla, but did not affect the levels of PENK mRNA in striatum, hypothalamus and hippocampus."	( Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and alpha 3 nicotinic receptor subunit in the rat. Höllt, V; Horn, G, )	1.26
"Nicotine is known to produce cutaneous vasoconstriction."	( Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption. Benowitz, NL; Jacob, P; Johansson, CJ; Olsson, P, 1992)	1.38
"Nicotine did not inhibit uptake of [3H]dopamine in the nucleus accumbens of saline-treated animals."	( Inhibition of dopamine uptake by cocaine and nicotine: tolerance to chronic treatments. Cox, BM; Izenwasser, S, 1992)	1.26
"Nicotine-induced increase in plasma catecholamines resulted in a powerful constriction of both resistance and oxygen-exchange vessels of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Skeletal muscle blood flow and O2 uptake during intravenous nicotine with and without hypertension. Hirsch, LJ; Rooney, MW, 1991)	1.24
"Nicotine alone did not produce catalepsy or any significant changes in locomotion."	( Nicotine potentiates the behavioral effects of haloperidol. Emerich, DF; Norman, AB; Sanberg, PR, 1991)	2.45
"Nicotine alone did not produce catalepsy."	( Nicotine potentiates haloperidol-induced catalepsy and locomotor hypoactivity. Emerich, DF; McConville, BJ; Norman, AB; Sanberg, PR; Zanol, MD, 1991)	2.45
"Nicotine may produce some of its effects through alterations in release of enkephalins from peripheral tissues."	( Nicotine-induced alterations in peripheral tissue concentrations of native and cryptic Met- and Leu-enkephalin. Houdi, AA; Pierzchala, K; Van Loon, GR, 1991)	2.45
"Nicotine did not increase repeated movements reliably."	( Locomotor activity in rats after administration of nicotinic agonists intracerebrally. Reavill, C; Stolerman, IP, 1990)	1
"Nicotine failed to produce any significant changes in the latencies of the FFP and EcoG components."	( [Effect of nicotine on auditory functions in the rat, studied by electrocochleography and auditory evoked potentials of the brain stem]. de Lavernhe-Lemaire, MC; Garand, G, 1985)	1.38
"The nicotine-induced increase in MHPG and DOPAC concentrations in the brain regions was inhibited by pretreatment with mecamylamine (5 mg/kg, i.p.) but not by hexamethonium (10 mg/kg, i.p.)."	( Nicotine-induced regional changes in brain noradrenaline and dopamine turnover in rats. Amano, H; Kubo, T; Kurahashi, K; Misu, Y, 1989)	2.2
"(-)-Nicotine-induced increase in catecholamine synthesis occurred by a direct stimulation of central nicotinic receptors, as mecamylamine (5 mg/kg) but not hexamethonium (5 mg/kg) was an effective antagonist."	( Regionally specific effects of acute and chronic nicotine on rates of catecholamine and 5-hydroxytryptamine synthesis in rat brain. Alavijeh, MS; Brazell, MP; Gray, JA; Joseph, MH; Mitchell, SN, 1989)	1.01
"The nicotine-induced increase in heart rate was larger during adenosine infusion than during placebo administration (14.9 versus 5.5 beats/min, p less than 0.001), whereas the increment of diastolic blood pressure was lower (1.1 versus 4.0 mm Hg, p less than 0.05)."	( Nicotine enhances the circulatory effects of adenosine in human beings. Eijsbouts, A; Smits, P; Thien, T, 1989)	2.2
"Nicotine from ST can activate the sympathetic nervous system thereby significantly increasing heart rate, blood pressure, cardiac stroke volume and output and coronary blood flow."	( Smokeless tobacco addiction: a threat to the oral and systemic health of the child and adolescent. Christen, AG; Christen, JA; McDonald, JL; Olson, BL, 1989)	1
"Nicotine was shown to produce significant increases in plasma AVP from 1.7 +/- 0.4 to 75.3 +/- 35.1 pg/ml (P less than .05) and in plasma ANF levels from 39 +/- 11 to 121 +/- 52 pg/ml (P less than .05) within 5 min of an i.v."	( Characterization of the effect of nicotine on vasopressin and atrial natriuretic factor in the rabbit. Cantin, M; du Souich, P; Januszewicz, P; Larose, P; Ong, H, 1988)	1.28
"Nicotine plays a key role in reinforcing tobacco smoking, and exerts several psychoneuropharmacological actions which may contribute to its reinforcing effects. "	( Nicotine and smoking: a perspective from animal studies. Clarke, PB, 1987)	3.16
"Nicotine tended to increase low ICSS rates but did not change or even reduced high ICSS rates."	( Effects of acute nicotine and ethanol on medial prefrontal cortex self-stimulation in rats. Arregui-Aguirre, A; Claro-Izaguirre, F; Goñi-Garrido, MJ; Morgado-Bernal, I; Zárate-Oleaga, JA, 1987)	1.33
"Nicotine did not cause contractions in the strip of the narrow portion of the cyst."	( Choledochal cyst. Its possible autonomic involvement in the bile duct. Ishikawa, Y; Kantoh, M; Kusunoki, M; Takahashi, T; Utsunomiya, J; Yamamura, T, 1987)	0.99
"Nicotine did not produce any change in the detection threshold for stimulation of the brain."	( Task-specific effects of nicotine in rats. Intracranial self-stimulation and locomotor activity. Michael, RP; Schaefer, GJ, 1986)	1.3
"Nicotine appeared to produce a concentration dependent desynchronization to ECoG activity in isolated perfused mouse brain (IPMB) from C3H mice."	( Nicotine alters catecholamines and electrocortical activity in perfused mouse brain. Cornell, K; Erwin, VG; Towell, JF, 1986)	2.44
"Nicotine cause a significant pressor response during infusion and a hypotensive response during the post infusion period."	( Effect of nicotine on blood flow, oxygen consumption and glucose uptake in the canine small intestine. Grayson, J; Oyebola, DD, 1985)	1.39

Treatment

Nicotine pretreatment affected the number of lymphocytes present in BAL after elastase instillation and some of the complement pathway related proteins. In nicotine+Histatin-1 treated cells, wound gap decreased to 70.2 ± 2.9% at 24 h. Nicotine treatment also downregulated the expression of α7nAChR in pregnant tissue.

Excerpt	Reference	Relevance
"Nicotine pretreatment affected the number of lymphocytes present in BAL after elastase instillation and some of the complement pathway related proteins, arguing for a slight modification of the immune response, as well as changes related to general body metabolism."	( Early life exposure to nicotine modifies lung gene response after elastase-induced emphysema. Avila, Y; Barazzone-Argiroffo, C; Blaskovic, S; Donati, Y; Ruchonnet-Metrailler, I; Schittny, D; Schittny, JC; Schlepütz, CM, 2022)	1.75
"In nicotine+Histatin-1 treated cells, wound gap decreased to 70.2 ± 2.9% (p < 0.01) at 24 h compared to nicotine alone in which 82 ± 1.64% of wound gap was retained."	( The efficacy of salivary Histatin-1 protein in wound closure of nicotine treated human periodontal ligament fibroblast cells - In vitro study. Aghila Rani, KG; Alkawas, S; Altell, RT; Arab, A; Ismail, AA; Samsudin, AR, 2022)	1.47
"Nicotine treatment also downregulated the expression of α7nAChR in pregnant tissue."	( Nicotine ameliorates inflammatory mediators in RU486 induced preterm labor model through activating cholinergic anti-inflammatory pathway. Bao, J; Garfield, RE; Huang, Q; Li, P; Liu, H; Ye, A, 2022)	2.89
"Nicotine-treated fish in which the medial part of the dorsal Hb was silenced did not have a higher winning rate, and nicotine-treated fish in which the lateral part of the dorsal Hb was silenced did not have a higher loss rate."	( Nicotine reduces social dominance and neutralizes experience-dependent effects during social conflicts in zebrafish (Danio rerio). Chou, MY; Chu, CY; Fu, CW; Huang, CH; Tong, SK, 2023)	3.07
"Nicotine treatment did not elicit different responses between sexes in the FST."	( Liver tryptophan 2,3-dioxygenase: a determinant of anxiety-like behaviour - studies with chronic nicotine administration in rats. Badawy, AA; Bano, S; Hamid, SB; Sajid, F; Sharif, H, 2023)	1.85
"Nicotine-treated rice plants were exposed to BPH (early stage) and the gut microbiome of the emerging female adults were analyzed using high throughput sequencing (HTS)."	( Nicotine perturbs the microbiota of brown planthopper (Nilaparvata lugens stål Hemiptera: Delphinidae). De Mandal, S; Gong, G; Hong, Y; Huang, L; Jin, F; Wang, X; Xu, X; Zafar, J, 2023)	3.07
"Nicotine treatment also induced changes in gene expression."	( Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice. Chen, GJ; Deng, XJ; Long, Y; Sun, F; Xu, DM; Yan, Z; Yang, J; Zhu, BL, 2019)	1.65
"Nicotine treatment also induced MEC apoptosis concurrently with inactivation of Akt."	( Nicotine directly affects milk production in lactating mammary epithelial cells concurrently with inactivation of STAT5 and glucocorticoid receptor in vitro. Kobayashi, K; Nishimura, T; Suzuki, N; Suzuki, T; Tsugami, Y, 2020)	2.72
"Nicotine treatment significantly increased the colocalization of NLRP3 with Asc, caspase-1 activity, IL-β production, cell permeability in podocytes compared to control cells. "	( Nicotine instigates podocyte injury via NLRP3 inflammasomes activation. Boini, KM; Koka, S; Kshirasagar, N; Patibandla, S; Puchchakayala, G; Singh, GB, 2019)	3.4
"D/N-nicotine-treated zebrafish obtained the highest CPP score, whereas zebrafish pre-exposed continuously to nicotine did not show nicotine-CPP."	( Pre-Exposure to Nicotine with Nocturnal Abstinence Induces Epigenetic Changes that Potentiate Nicotine Preference. Bernabeu, R; Faillace, MP; Pisera-Fuster, A, 2020)	1.38
"Nicotine-treated S."	( Effect of nicotine on Staphylococcus aureus biofilm formation and virulence factors. Huang, W; Ma, Y; Qu, D; Shi, L; Wang, JX; Wu, Y; Yan, YJ; Yang, C; Zhang, QZ; Zhao, KQ; Zheng, CQ; Zhu, T; Zhu, XY, 2019)	1.64
"Nicotine treatment normalizes these levels in hypothyroid rats trained on both the visible and hidden platforms."	( Comparison of Effects of Spatial and Non-Spatial Memory Acquisition on the CaMKII Pathway During Hypothyroidism and Nicotine Treatment. Alkadhi, KA; Alzoubi, KH, 2020)	1.49
"Nicotine treatment accelerated cell cycle progression in the oral cancer cells, and significantly reduced cisplatin-induced cell apoptosis."	( α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer. Chen, YC; Chien, CY; Hsu, CC; Liu, SY; Shieh, YS; Su, YF; Tsai, KY; Wu, YC, 2020)	1.9
"The nicotine-treated group showed significantly decreased epididymal sperm density and serum testosterone concentration relative to the control group. "	( Evaluation of the protective effects of icariin on nicotine-induced reproductive toxicity in male mouse -a pilot study. Afedo, SY; Ni, G; Rui, R; Zhang, X, 2020)	1.37
"Nicotine treatment reduced SKOV3 and TOV112D spheroid invasion and compaction but did not significantly affect spheroid formation."	( Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells. Bouni, ME; Chadee, DN; Harmych, SJ; Kumar, J, 2020)	2.72
"Nicotine treatment increased the decreased M2 phenotype and inhibited the increased M1 phenotype in decidua of pregnant mice induced by LPS."	( Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model. Guo, K; Han, X; He, P; Li, P; Li, W; Lin, B; Yang, J; Zheng, Z; Zhou, B, 2021)	1.59
"Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis?"	( A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis. Baran, J; Crouser, ED; Culver, DA; Diaz, C; Erdal, BS; Hade, EM; Julian, MW; Martin, K; Smith, RM, 2021)	1.51
"Nicotine treatment was associated with a clinically significant, approximately 2.1% (70 mL) improvement in FVC from baseline to 26 weeks. "	( A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis. Baran, J; Crouser, ED; Culver, DA; Diaz, C; Erdal, BS; Hade, EM; Julian, MW; Martin, K; Smith, RM, 2021)	2.33
"Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC."	( A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis. Baran, J; Crouser, ED; Culver, DA; Diaz, C; Erdal, BS; Hade, EM; Julian, MW; Martin, K; Smith, RM, 2021)	2.33
"Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells."	( Disruption of retinal pigment epithelial cell properties under the exposure of cotinine. Brelén, ME; Cao, D; Chan, KP; Chan, SO; Ng, TK; Pang, CP; Wang, Y; Wu, D; Yung, JSY; Zhang, S; Zhang, XY, 2017)	0.91
"Nicotine-treated IC rats self-administered more d-amphetamine at 0.006, 0.01, and 0.02 mg/kg/infusion doses compared with their saline-treated IC counterparts regardless of the schedule maintaining behavior."	( Effects of environmental enrichment on d-amphetamine self-administration following nicotine exposure. Ewin, SE; Kangiser, MM; Pfaff, MN; Stairs, DJ, 2017)	1.4
"Nicotine treatment effects were observed on CRF1R levels in the DS."	( Increased expression of CRF and CRF-receptors in dorsal striatum, hippocampus, and prefrontal cortex after the development of nicotine sensitization in rats. Bate, ST; Carboni, L; Romoli, B; Romualdi, P; Zoli, M, 2018)	1.41
"Nicotine treatment significantly attenuated MAdCAM-1 expression, leukocyte recruitment, DAI, and histological score."	( Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. Furuhashi, H; Higashiyama, M; Hokari, R; Hozumi, H; Ishizuka, T; Komoto, S; Kurihara, C; Maruta, K; Miura, S; Nagao, S; Okada, Y; Shirakabe, K; Takajo, T; Tomita, K; Watanabe, C, 2018)	2.64
"Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines."	( Roles of Nicotine in the Development of Intracranial Aneurysm Rupture. Furukawa, H; Hashimoto, T; Kamio, Y; Kimura, T; Korai, M; Kudo, D; Lawton, MT; Lukas, RJ; Mitsui, K; Miyamoto, T; Yokosuka, K; Zhang, D, 2018)	1.62
"The nicotine treatment decreased BDNF levels in the prefrontal cortex but had no effect on striatal BDNF."	( Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation. Kohtala, S; Koski, SK; Leino, S; Rannanpää, S; Rantamäki, T; Salminen, O, 2018)	0.96
"Nicotine treatment induced HSC-2 cell proliferation and migration and the phosphorylation of EGFR."	( Nicotine exposure induces the proliferation of oral cancer cells through the α7 subunit of the nicotinic acetylcholine receptor. Chen, C; Ibaragi, S; Nishioka, T; Sasano, T; Tada, H, 2019)	2.68
"Nicotine treatment led to overproduction of reactive oxygen species (ROS), which formed intracellular oxidative stress that could induce the expression of several antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and peroxiredoxin (Prx)."	( Transcriptome analysis of genes and metabolic pathways associated with nicotine degradation in Aspergillus oryzae 112822. He, C; Huang, Y; Liu, P; Wei, J; Xiao, M; Xu, L; Yang, Y, 2019)	1.47
"Nicotine-treated animals did not differ from control animals in gross motor performance or millet seed intake, although female mice consumed more millet seeds than male mice when reaching was not required."	( Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Lee, AM; Picciotto, MR, 2019)	1.64
"Nicotine treatment reduced mechanical allodynia, cartilage degradation, and the upregulation of matrix metalloproteinase-9 (MMP-9), a hallmark of joint inflammation in OA, in mice treated with monosodium iodoacetate."	( Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor. Dai, Y; Hu, J; Liu, WT; Liu, Y; Teng, P; Zhang, H, 2019)	2.68
"Some nicotine-treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment."	( Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions. Domen, T; Imamura, T; Ishizuka, O; Minagawa, T; Nagai, T; Ogawa, T; Suzuki, T; Ueno, M, 2019)	2.41
"Nicotine-treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls."	( Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions. Domen, T; Imamura, T; Ishizuka, O; Minagawa, T; Nagai, T; Ogawa, T; Suzuki, T; Ueno, M, 2019)	2.68
"Nicotine-treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. "	( Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions. Domen, T; Imamura, T; Ishizuka, O; Minagawa, T; Nagai, T; Ogawa, T; Suzuki, T; Ueno, M, 2019)	3.4
"Nicotine treatment increased ACh levels to a larger extent in females than males."	( Sex differences in cholinergic systems in the interpeduncular nucleus following nicotine exposure and withdrawal. Arreguin, MC; Carcoba, LM; Correa, VL; Flores, RJ; O'Dell, LE, 2019)	1.46
"Nicotine-treated rats gained half the weight that vehicle treated animals gained and ate approximately 20 % less food overall than vehicle-treated rats. "	( The effects of extended intravenous nicotine administration on body weight and meal patterns in male Sprague-Dawley rats. Grebenstein, PE; Rowland, NE; Thompson, IE, 2013)	2.11
"In nicotine treated wild-type mice, both α4β2* and α7 nAChR binding sites were increased compared with saline treated controls."	( Genetic deletion of the adenosine A(2A) receptor prevents nicotine-induced upregulation of α7, but not α4β2* nicotinic acetylcholine receptor binding in the brain. Al-Hasani, R; Bailey, A; Berwick, A; Farshim, P; Hourani, S; Kitchen, I; Ledent, C; Metaxas, A; Tubby, K, 2013)	1.15
"Nicotine treatment (20 µM and 20 mM) was limited to the post-embryonic stage from L1 to L4 (∼31 h) period after which worms were collected for genome-wide miRNA profiling."	( Chronic nicotine exposure systemically alters microRNA expression profiles during post-embryonic stages in Caenorhabditis elegans. Pan, X; Taki, FA; Zhang, B, 2014)	1.56
"Nicotine treatment minimally impacted expression of cytokines and cytolytic activity."	( Combustible and non-combustible tobacco product preparations differentially regulate human peripheral blood mononuclear cell functions. Arimilli, S; Damratoski, BE; Prasad, GL, 2013)	1.11
"Nicotine pretreatment may be protective in sporadic PD patients and models; however, timely diagnosis remains to be an obstacle."	( Nicotine increases lifespan and rescues olfactory and motor deficits in a Drosophila model of Parkinson's disease. Buhlman, LM; Call, GB; Chambers, RP; Meyer, D; Pearman, K; Smith, J; Techau, JA, 2013)	2.55
"Nicotine pretreatment affects reward-related behavior in both an age- and reward-dependent manner. "	( Age-dependent alterations in reward-seeking behavior after brief nicotine exposure. Belluzzi, JD; Leslie, FM; Mojica, CY, 2014)	2.08
"Nicotine-treated rats showed significant (P < .001) cervical resistance to stretch and higher LIF compared with the control rats."	( Nicotine treatment prolongs gestation and inhibits cervical ripening in pregnant rats. Fang, D; Garfield, RE; Liu, H; Shi, L; Shi, SQ; Yang, J, 2014)	2.57
"Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only."	( Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response. Dao, JM; Leslie, FM; Loughlin, SE; Mojica, CY; Yuan, M, 2014)	2.57
"The nicotine-treated females were then bred with drug-naive males, and the embryos and larvae were grown in a nicotine-free environment."	( Impact of maternal nicotine exposure on expression of myelin-related genes in zebrafish larvae. Cao, J; Cui, WY; Fan, L; Li, MD; Luo, C; Zhao, S, 2014)	1.21
"Nicotine-treated MSCs had a significantly higher G0/G1 ratio (P < 0.05)."	( Effects of nicotine on proliferation and survival in human umbilical cord mesenchymal stem cells. Bu, QQ; Chen, HZ; Chen, J; Han, XA; Li, Y; Liu, GX; Qin, YL; Yu, PX; Zeng, HL; Zhong, Q, 2014)	1.51
"Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region."	( Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation. Li, XH; Liu, F; Liu, L; Qin, HQ; Wang, H; Wang, JF; Yan, YE, 2014)	1.12
"Nicotine treatment significantly reduces LPS-induced TNF-α and IL-6 concentrations (P < .001) but does not change (P > .05) IL-10 levels."	( Nicotine, an α7 nAChR agonist, reduces lipopolysaccharide-induced inflammatory responses and protects fetuses in pregnant rats. Fang, D; Garfield, RE; Liu, H; Shi, L; Shi, SQ; Yang, J, 2014)	2.57
"The nicotine treatment group experienced an average decrease in total retinal thickness (TRT) of 9.4 µm with the majority of the loss localized within the outer nuclear layer (ONL) as determined by segmentation analysis (p < 0.05)."	( Nicotine accelerates diabetes-induced retinal changes. Boretsky, A; Godley, BF; Gupta, P; Liu, R; Motamedi, M; Tilton, RG; Tirgan, N; Zhang, W, 2015)	2.34
"Nicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC20-P) levels. "	( Perinatal nicotine exposure increases angiotensin II receptor-mediated vascular contractility in adult offspring. Dasgupta, C; Huang, X; Li, Y; Xiao, D; Zhang, L, 2014)	2.25
"Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells."	( Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism. Bijli, KM; Crothers, K; Fitzpatrick, AM; Grooms, K; Hart, CM; Wongtrakool, C, 2014)	2.57
"Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6."	( Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis. Cheng, Z; Jing-Lin, Z; Li-Sha, G; Wen-Wu, Z; Xing-Xing, C; Xue-Si, C; Yue-Chun, L, 2014)	1.12
"The nicotine treatment did not reverse the level of ChAT but significantly inhibited the decrease in HC-3 binding, indicating improvement of cholinergic function without affecting the number of ACh terminals."	( Effect of nicotine on neuronal dysfunction induced by intracerebroventricular infusion of amyloid-β peptide in rats. Murayama, N; Nakamura, S; Noshita, T, 2015)	1.3
"In nicotine treatment group, nicotine (50, 100, and 300 μg/kg) was administered 1 hour before and after SAP operation through intraperitoneal injection."	( Nicotine ameliorates experimental severe acute pancreatitis via enhancing immunoregulation of CD4+ CD25+ regulatory T cells. Ke, L; Li, JS; Li, N; Li, WQ; Wu, ZS; Zhang, LY; Zheng, YS, 2015)	2.37
"Nicotine or MDMA treatment reduced memory function and altered hippocampal structure."	( Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment. Adeniyi, PA; Bankole, OO; Ishola, AO; Laoye, BJ; Ogundele, OM; Olatunji, BP; Shallie, PD, 2016)	1.39
"Nicotine treatment ameliorated cartilage destruction, promoted matrix production, reduced the serum level of TNF-α and the expression of TNF-α in the synovial tissue, and increased the expression of α7nAChR in the synovial tissue in the rat model of early stage OA."	( Effects of nicotine on a rat model of early stage osteoarthritis. Gu, Q; Guo, Y; Li, D; Mao, F; Wang, L; Wei, B; Yan, J; Zhang, X, 2015)	1.53
"Nicotine treatment did not alter cocaine versus food choice."	( Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys. Banks, ML; Negus, SS; Poklis, JL; Schwienteck, KL, 2015)	1.45
"Nicotine treated group showed least performance in learning in comparison with control, atorvastatin and atorvastatin+nicotine treated groups."	( Atorvastatin improves Y-maze learning behaviour in nicotine treated male albino rats. Das S, S; Febi, J; Indira, M; Kavitha, S; Nair, SS, 2015)	1.39
"The nicotine treatment significantly decreased body weight, total glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and increased malondialdehyde (MDA) and nitric oxide (NO) levels in the N group compared to controls."	( Investigation of the protective effect of ellagic acid for preventing kidney injury in rats exposed to nicotine during the fetal period. Akkoyun, HT; Karadeniz, A, 2016)	1.13
"Nicotine treatment led to dose-dependent increases in the phosphorylation of PERK[Thr981] and eIF2α[Ser51], whereas pretreatment with a nicotinic acetylcholine receptor (nAChR) antagonist (mecamylamine hydrochloride) blocked the induction of PERK phosphorylation, verifying the direct involvement of nicotine and nAChR binding."	( Nicotine Directly Induces Endoplasmic Reticulum Stress Response in Rat Placental Trophoblast Giant Cells. Hardy, DB; Holloway, AC; Wong, MK, 2016)	2.6
"Nicotine treatment reduced cell viability dose dependently, increased ROS levels, and increased extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK expression."	( Nicotine-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells. Bae, EH; Choi, JS; Joo, SY; Kim, CS; Kim, SW; Lee, J; Ma, SK, 2016)	2.6
"The nicotine treatment group showed an increase in collagen IV secondary papillae and basal cells."	( Effects of Nicotine on Rat Tongue Mucosa. Histopathological and Immunohistochemical Analyses. Deveci, E; Eratilla, E; Eratilla, V; Güneş, RF; Söker, S; Uysal, I; Yildiz, I, 2016)	1.31
"In nicotine-treated PC cells, the aPKC was significantly activated."	( Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C. Amisaki, M; Arai, Y; Hanaki, T; Honjo, S; Horikoshi, Y; Ikeguchi, M; Kitagawa, Y; Matsura, T; Nakaso, K; Nakasone, M; Ohno, S; Saito, H; Sakamoto, T; Tokuyasu, N; Yamashita, K, 2016)	2.39
"Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. "	( Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily. Carroll, FI; Cunningham, CS; Javors, MA; McMahon, LR; Moerke, MJ, 2016)	2.27
"Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells."	( Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3. Du, P; Liu, X; Qin, Z; Su, DF; Sun, Y; Wan, JJ; Wang, PY; Wu, T; Yang, Y, 2017)	2.62
"Nicotine treatment decreased the levels of LPS-induced pro-inflammatory cytokines in the serum (P < 0.05) and placenta (P < 0.05)."	( Activation of the cholinergic anti-inflammatory pathway by nicotine ameliorates lipopolysaccharide-induced preeclampsia-like symptoms in pregnant rats. Bao, J; Li, X; Liu, H; Liu, Y; Yang, J; Ye, A; Zhang, G, 2017)	1.42
"Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment."	( Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats. Asanuma, M; Kanemoto, E; Kanzaki, H; Kitamura, Y; Machida, A; Miyazaki, I; Naito, N; Nakamura, Y; Sendo, T; Sugimoto, M, 2017)	1.55
"Upon nicotine treatment, the mRNA level of RhoGDIA is increased but protein level is decreased both in vitro and in vivo, which suggested a mechanism of post-translational regulation."	( Nicotine facilitates VSMC dysfunction through a miR-200b/RhoGDIA/cytoskeleton module. Hou, S; Liang, D; Qiao, Z; Shang, M; Wang, L; Wang, Z; Xu, W; Yan, Z, 2017)	2.35
"In nicotine treated fish and cells a negative correlation between reduced glutathione and LPO was observed."	( Effects of nicotine on zebrafish: A comparative response between a newly established gill cell line and whole gills. Abdul Majeed, S; Nathiga Nambi, KS; Sahul Hameed, AS; Sarath Babu, V; Sivasubbu, S; Taju, G, 2017)	1.36
"Nicotine treatment in adulthood produced an immediate increase in AC activity in males that disappeared upon withdrawal; there were late-emerging deficits similar to, but smaller in magnitude than those seen with adolescent nicotine exposure."	( Adolescent nicotine administration changes the responses to nicotine given subsequently in adulthood: adenylyl cyclase cell signaling in brain regions during nicotine administration and withdrawal, and lasting effects. Bodwell, BE; Mackillop, EA; Ryde, IT; Seidler, FJ; Slotkin, TA, 2008)	1.46
"Nicotine-treated mice showed up-regulation of epibatidine binding in several brain regions."	( Opposing actions of chronic stress and chronic nicotine on striatal function in mice. De Biasi, M; Salas, R, 2008)	1.32
"Nicotine treatment has long been associated with alterations in alpha4beta2(*) nicotinic acetylcholine receptor (nAChR) expression that modify dopaminergic function. "	( Long-term nicotine treatment differentially regulates striatal alpha6alpha4beta2* and alpha6(nonalpha4)beta2* nAChR expression and function. Bordia, T; Grady, SR; McIntosh, JM; Perez, XA; Quik, M, 2008)	2.19
"Nicotine-treated rats also made more correct responses and fewer omissions than vehicle-treated rats."	( Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration. Amitai, N; Markou, A, 2009)	1.51
"Nicotine treatment also significantly reduced AIMs in L-DOPA-primed rats using either dosing regimen, whereas nicotine removal led to an increase in AIMs."	( Continuous and intermittent nicotine treatment reduces L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias in a rat model of Parkinson's disease. Bordia, T; Campos, C; Huang, L; Quik, M, 2008)	1.36
"Nicotine pretreatment reversed the anti-lipid peroxidative action of sodium valproate in the PTZ-induced seizure model in mice."	( Dose-finding study with nicotine as a proconvulsant agent in PTZ-induced seizure model in mice. Chakrabarti, A; Medhi, B; Sahai, AK; Sood, N, 2008)	1.37
"The nicotine treatment significantly but temporarily decreased substance P-like immunoreactivity (SPLI) content in the ventral tegmental area (VTA) and substantia nigra 12-18 h after drug exposure. "	( Responses of limbic and extrapyramidal substance P systems to nicotine treatment. Alburges, ME; Frankel, PS; Hanson, GR; Hoonakker, AJ, 2009)	1.15
"In nicotine-pretreated mice, morphine-induced dopamine release in the caudate putamen and nucleus accumbens was significantly augmented, as measured by microdialysis."	( Chronic nicotine modifies the effects of morphine on extracellular striatal dopamine and ventral tegmental GABA. Ahtee, L; Airavaara, M; Leiviskä, R; Piepponen, TP; Relander, TR; Tuominen, RK; Vihavainen, T, 2008)	1.29
"Nicotine treatment was associated with a transiently enhanced growth of S."	( Stimulation of acetylcholine receptors impairs host defence during pneumococcal pneumonia. Florquin, S; Giebelen, IA; Leendertse, M; van der Poll, T, 2009)	1.07
"Nicotine treatment was repeated on day 6 to test for tolerance."	( Chronic menthol attenuates the effect of nicotine on body temperature in adolescent rats. Anand, R; LaHoste, GJ; Ruskin, DN, 2008)	1.33
"Nicotine treatment altered both non-burst- and burst-stimulated dopamine release in ventral but not dorsal putamen."	( Prominent role of alpha3/alpha6beta2* nAChRs in regulating evoked dopamine release in primate putamen: effect of long-term nicotine treatment. McIntosh, JM; O'Leary, KT; Parameswaran, N; Perez, XA; Quik, M, 2009)	1.28
"Nicotine pre-treatment attenuated behavioral deficits and lessened lesion-induced losses of the striatal dopamine transporter, and alpha6beta2* and alpha4beta2* nicotinic receptors (nAChRs)."	( Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys. Bordia, T; Huang, LZ; Michael McIntosh, J; Parameswaran, N; Quik, M, 2009)	2.52
"Nicotine pretreatment had no impact on cerebral or cardiac histopathology."	( Newborn piglets exposed to hypoxia after nicotine or saline pretreatment: long-term effects on brain and heart. Andresen, JH; Carlsen, B; Goverud, IL; Løberg, EM; Mørkrid, L; Saugstad, OD; Solberg, R, 2009)	1.34
"Nicotine pretreatment (0.4, 0.8 and 1.2 mg/kg) increased voluntary ethanol intake on day 10 by 1.8, 2.0, and 1.4 fold respectively compared to saline pretreatment (P<0.01-0.3)."	( Differential induction of ethanol-metabolizing CYP2E1 and nicotine-metabolizing CYP2B1/2 in rat liver by chronic nicotine treatment and voluntary ethanol intake. Khokhar, J; Miksys, S; Tyndale, RF; Yue, J, 2009)	1.32
"Nicotine treatment reversed these impairments whereas carbachol did not."	( The role of the AT4 and cholinergic systems in the Nucleus Basalis Magnocellularis (NBM): effects on spatial memory. Harding, JW; Munn, C; Ross, RC; Wilson, WL; Wright, JW, 2009)	1.07
"Nicotine treatment resulted in sensitization and conditioned hyperactivity in all differential rearing groups."	( Effects of mecamylamine on nicotine-induced conditioned hyperactivity and sensitization in differentially reared rats. Cain, ME; Coolon, RA, 2009)	1.37
"Nicotine treatment resulted in a marked reduction in lung allograft infiltration by CD68-like antigen(+) alveolar and tissue macrophages, whereas resident mature macrophages (CD163(+)) and T cells remained unchanged. "	( Nicotine attenuates macrophage infiltration in rat lung allografts. Grau, V; Hirschburger, M; Kummer, W; Padberg, W; Zakrzewicz, A, 2009)	3.24
"Nicotine treatment of PDA cells selectively induced de novo expression of OPNc. "	( Expression of a prometastatic splice variant of osteopontin, OPNC, in human pancreatic ductal adenocarcinoma. Alnajar, A; Arafat, HA; Aziz, T; Blair, L; Chipitsyna, G; Denhardt, DT; Gong, Q; Ng, CY; Sullivan, J; Weber, GF; Witkiewicz, A; Yeo, CJ, 2009)	1.8
"Nicotine treatment concomitantly downregulated the expression of OPG and osteoblastic differentiation markers, such as alkaline phosphatase, osteocalcin, and osteopontin, and upregulated the expression of RANKL. "	( Effects of nicotine on antioxidant defense enzymes and RANKL expression in human periodontal ligament cells. Kim, EC; Kim, HS; Kim, SJ; Kim, Y; Kim, YS; Lee, HJ; Lee, SK; Pi, SH, 2009)	2.19
"Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys."	( Chronic nicotine treatment increases nAChRs and microglial expression in monkey substantia nigra after nigrostriatal damage. Campos, C; Langston, JW; McIntosh, JM; Parameswaran, N; Quik, M; Yeluashvili, M, 2010)	1.52
"Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. "	( Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats. Belluzzi, JD; Dao, JM; Leslie, FM; McQuown, SC, 2009)	2.07
"Nicotine or saline treatment was preceded by the D2-like receptor antagonist eticlopride, D3 antagonist nafadotride, or saline."	( Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: role of D2 and D3 receptor subtypes. Brown, RW; Cope, ZA; Lehmann, J; Sheppard, B, 2009)	1.4
"Nicotine treatment increased the expressions of COX-2 at mRNA and protein level in a dose-dependent manner, following prostaglandin E(2) (PGE(2)) release enhancement."	( Nicotine induces cyclooxygenase-2 and prostaglandin E(2) expression in human umbilical vein endothelial cells. Qiao, ZD; Tang, MP; Wang, LY; Wang, ZX; Xu, WJ; Yao, CJ; Zhou, Y, 2010)	2.52
"Nicotine treatment increased correlations in both sexes, and yielded a significant negative interaction between initial ambulatory counts and plasma corticosterone."	( Locomotor and stress responses to nicotine differ in adolescent and adult rats. Belluzzi, JD; Cao, J; Chen, Y; Dao, JM; Leslie, FM; Loughlin, SE, 2010)	1.36
"Nicotine treatment stimulated the promoter activity of Egr-1 in cultured human fibroblasts."	( Nicotine induces the expression of early growth response-1 in human skin dermal fibroblasts. Choi, JE; Jeong, SH; Kim, JN; Son, SW, 2010)	2.52
"Nicotine treatment significantly increased MCP-1 expression in PDA cells. "	( Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: role of osteopontin. Arafat, HA; Aziz, T; Chipitsyna, G; Denhardt, DT; Gong, Q; Lazar, M; Salem, AF; Sullivan, J; Witkiewicz, A; Yeo, CJ, 2010)	2.06
"Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein."	( Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury. Gordon, S; Mabley, J; Pacher, P, 2011)	2.53
"Nicotine pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α, IL-1β and HMGB-1 in mice with ALI. "	( Protective effect of nicotine on lipopolysaccharide-induced acute lung injury in mice. Fu, HY; Jiang, T; Lu, ZF; Ni, YF; Tian, F; Wang, J; Wang, YJ; Yan, XL; Yang, GD; Zhao, YC, 2011)	2.13
"nicotine treatment of pregnant rats starting at day 4 of gestation increased the methylation of the Egr-1 binding site at the PKCε gene promoter and decreased PKCε protein and mRNA abundance in near-term foetal hearts. "	( Foetal nicotine exposure causes PKCε gene repression by promoter methylation in rat hearts. Buchholz, JN; Chen, M; Lawrence, J; Xiao, D; Xiong, F; Zhang, H; Zhang, L, 2011)	2.27
"Nicotine treatment has known to produce an inverse relationship between body weight and food intake in rodents. "	( High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice. Choi, SH; Chun, BG; Hong, GH; Hur, YN; Shin, KH, 2010)	2.04
"Nicotine treatment induced marked endothelial damage and an obvious vasoconstriction in the aorta as evaluated by an increased endothelin-1 (ET-1) expression. "	( Endothelin-1 as a potential marker of melatonin's therapeutic effects in smoking-induced vasculopathy. Favero, G; Foglio, E; Reiter, RJ; Rezzani, R; Rodella, LF; Rossini, C, 2010)	1.8
"Nicotine-treated rats also learned the discrimination in fewer sessions than control rats."	( Differential effects of nicotinic acetylcholine receptor stimulation on negative occasion setting. Bucci, DJ; MacLeod, JE; Vucovich, MM, 2010)	1.08
"Nicotine-treated imDCs might be considered as a potential candidate for therapeutic tumor immunotherapy for lung and liver cancer."	( Nicotine stimulated dendritic cells could achieve anti-tumor effects in mouse lung and liver cancer. Gao, FG; Gu, JR; Li, HT; Li, ZJ, 2011)	2.53
"Nicotine pretreatment sensitized AMPH-induced DA overflow in slices from ventral (nucleus accumbens, NAc), but not dorsal striatum as compared to saline-pretreated rats."	( The sensitizing effect of acute nicotine on amphetamine-stimulated behavior and dopamine efflux requires activation of β2 subunit-containing nicotinic acetylcholine receptors and glutamate N-methyl-D-aspartate receptors. Gnegy, ME; Jutkiewicz, EM; Kim, MN; Zhang, M, 2011)	1.37
"Nicotine treatment induced a statistically significant increased expression of E2F-regulated genes in A549-EV but not in A549-sh cells; the maximum difference being observed in BIRC5 (A549-EV vs A549-sh, mean fold-increase in mRNA level upon nicotine treatment = 20.7-fold, 95% confidence interval = 19.2- to 22.2-fold, vs mean = 0.8-fold, 95% confidence interval= 0.78- to 0.82-fold, P < .001)."	( ARRB1-mediated regulation of E2F target genes in nicotine-induced growth of lung tumors. Banerjee, S; Chellappan, SP; Coppola, D; Dasgupta, P; Davis, R; Haura, E; Hug, K; Lloyd, M; Pillai, S; Rizwani, W, 2011)	1.34
"Nicotine treatment (0.4 mg·kg⁻¹·da⁻¹, 10 days) increased more than 100-fold the potency of bPiDI (IC₅₀=1.45 nM) to inhibit nicotine-evoked dopamine release."	( bPiDI: a novel selective α6β2* nicotinic receptor antagonist and preclinical candidate treatment for nicotine abuse. Bardo, MT; Crooks, PA; Dwoskin, LP; McIntosh, JM; Pivavarchyk, M; Siripurapu, KB; Smith, AM; Wooters, TE; Zhang, Z, 2011)	1.31
"In nicotine-treated rats, the threshold intensity of NBM stimulation producing increases in acetylcholine release and blood flow was reduced to 20μA."	( Sustained subcutaneous infusion of nicotine enhances cholinergic vasodilation in the cerebral cortex induced by stimulation of the nucleus basalis of Meynert in rats. Hotta, H; Kawashima, K; Misawa, H; Uchida, S, 2011)	1.16
"Nicotine treatment was associated with a highly significant decrease in pain reported during the 5 days after TM surgery. "	( Nicotine nasal spray as an adjuvant analgesic for third molar surgery. Afzali, P; Akkara, J; Alfi, DM; Conell-Price, J; Eisig, SB; Flood, P; Olson, L; Yagoubian, B; Yeh, J, 2011)	3.25
"Nicotine pretreatment aggravated the arthritis, whereas nicotine posttreatment suppressed the disease. "	( Nicotine-induced differential modulation of autoimmune arthritis in the Lewis rat involves changes in interleukin-17 and anti-cyclic citrullinated peptide antibodies. Moudgil, KD; Rajaiah, R; Yang, YH; Yu, H, 2011)	3.25
"Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32."	( Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism. Belluzzi, JD; Dao, JM; Leslie, FM; Loughlin, SE; McQuown, SC, 2011)	2.53
"Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations (0.1, 0.3mM) but tolerance at higher concentrations (1, 3mM)."	( Nicotine behavioral pharmacology: clues from planarians. Baron, S; Kim, M; Patil, T; Raffa, RB; Rawls, SM; Song, K; Tallarida, CS; Ward, S, 2011)	2.53
"Nicotine treatment selectively induced denovo expression of OPNc and increased α7-nAChR expression levels."	( Expression and regulation of nicotine receptor and osteopontin isoforms in human pancreatic ductal adenocarcinoma. Alnajar, A; Arafat, HA; Aziz, T; Blair, L; Chipitsyna, G; Gong, Q; Sullivan, J; Yeo, CJ, 2011)	1.38
"The nicotine treatment significantly decreased the superoxide dismutase activity and increased malondialdehyde, superoxide and nitrotyrosine protein levels in the vascular wall."	( Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring. Huang, X; Xiao, D; Yang, S; Zhang, L, 2011)	1.25
"In nicotine and PD98059 treated group, the PAI-1 mRNA and protein expression [(1.12 ± 0.11), (17.52 ± 1.72) µg/L] decreased significantly compared to the nicotine treated group(q = 4.68, 5.54, all P < 0.05), still higher than the control group (q = 8.77, 6.43, all P < 0.05)."	( [Interaction of protein kinase C-extracellular signal-regulated kinase 1/2 signal pathway in the process of plasminogen activator inhibitor-1 expression induced by nicotine in human umbilical vein endothelial cells]. DU, Y; DU, YC; Han, BF; Hu, XY, 2011)	1.08
"Nicotine pretreatment caused dose-dependent antagonism to the antiseizure and antilipid peroxidative actions of topiramate."	( Nicotine reversal of anticonvulsant action of topiramate in kainic acid-induced seizure model in mice. Chakrabarti, A; Hota, D; Sahai, AK; Sood, N, 2011)	2.53
"Nicotine treatment (0.01-1 μM) for up to 48 h had little or no effect upon the TEER or sucrose permeability of either ECV304/C6 co-cultures or CaCo₂ cells."	( Comparison of the effects of nicotine upon the transcellular electrical resistance and sucrose permeability of human ECV304/rat C6 co-cultures and human CaCo₂ cells. Alvehus, M; Andersson, T; Jacobsson, SO; Rodriguez-Gaztelumendi, A, 2011)	1.38
"Nicotine treatment increased VSMC chemotaxis to serum-free medium, but TSP-1 or Fn had no further effect on chemotaxis. "	( The effects of nicotine on vascular smooth muscle cell chemotaxis induced by thrombospondin-1 and fibronectin. Gahtan, V; Maier, KG; Seymour, KA; Stein, JJ, 2011)	2.16
"Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism."	( Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons. Akay, M; Akay, Y; Chen, T; Dragomir, A; Kobayashi, K; Zhang, D, 2011)	1.34
"In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect."	( The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration. Bora, NS; Bora, PS; Davis, SJ; Lyzogubov, VV; Safar, AN; Tytarenko, RG, 2012)	1.25
"Nicotine pretreatment had no effect on ADs duration in 12-day-old pups, therefore brought about suppression of ADs in 35-day-old animals."	( Nicotine reduces mortality of developing rats exposed to high-altitude hypoxia and partially suppresses the duration of cortical epileptic afterdischarges. Marešová, D; Pokorný, J; Riljak, V, 2011)	2.53
"Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks."	( Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats. Bordia, T; McIntosh, JM; Quik, M, 2012)	2.54
"Nicotine-treated mGluR5(+/+) and mGluR5(-/-) mice demonstrated similar threshold elevations during mecamylamine-precipitated withdrawal compared with their saline-treated counterparts. "	( Involvement of metabotropic glutamate receptor 5 in brain reward deficits associated with cocaine and nicotine withdrawal and somatic signs of nicotine withdrawal. Markou, A; Olivier, B; Stoker, AK, 2012)	2.04
"The nicotine-treated group showed an enhanced level of stress neurotransmitters and second messenger cAMP in serum, blood cellular fraction, and xenograft tissues."	( Gamma-amino butyric acid inhibits the nicotine-imposed stimulatory challenge in xenograft models of non-small cell lung carcinoma. Al-Wadei, HA; Al-Wadei, MH; Schuller, HM; Ullah, MF, 2012)	1.13
"Nicotine-treated NSCLC cells showed significant induction of the α7nAChR and α4nAChR, along with significant inductions of p-CREB and p-ERK1/2 accompanied by increases in the stress neurotransmitter noradrenaline, which in turn led to the observed increase in DNA synthesis and cell proliferation."	( Cooperative regulation of non-small cell lung carcinoma by nicotinic and beta-adrenergic receptors: a novel target for intervention. Al-Wadei, HA; Al-Wadei, MH; Schuller, HM, 2012)	1.1
"Nicotine pretreatments increased the dopamine-stimulating effects of ethanol in the pVTA (100 mg% ethanol: 115% vs 160% of baseline in the vehicle and nicotine groups, respectively, p < 0.05; 200 mg% ethanol: 145% vs 190% of baseline in the vehicle and nicotine groups, respectively, p < 0.05)."	( Repeated exposure of the posterior ventral tegmental area to nicotine increases the sensitivity of local dopamine neurons to the stimulating effects of ethanol. Deehan, GA; Ding, ZM; Engleman, EA; Hauser, SR; Katner, SN; McBride, WJ; Rodd, ZA; Truitt, W, 2012)	1.34
"The nicotine treatments had no effect on pituitary and plasma β-endorphin."	( Nicotine-induced changes of brain β-endorphin. Duchemin, AM; Gudehithlu, KP; Hadjiconstantinou, M; Neff, NH; Tejwani, GA, 2012)	2.3
"Nicotine treatment led to the downregulation of ECM molecules, including collagen type I, elastin and fibronectin, and upregulation of MMPs (MMP-1, MMP-2, MMP-8 and MMP-9)."	( Endoplasmic reticulum stress modulates nicotine-induced extracellular matrix degradation in human periodontal ligament cells. Herr, Y; Kang, KL; Kim, EC; Lee, SI; Lee, YM; Shin, SI, 2012)	1.37
"Nicotine treated mice, 78.6%, but none of control of mice, developed neoplasms originating from the uterus or skeletal muscle. "	( Muscle sarcomas and alopecia in A/J mice chronically treated with nicotine. Chernyavsky, AI; Edwards, RA; Galitovskiy, V; Grando, SA, 2012)	2.06
"Nicotine treatment transiently induced translation of GluR2 mRNA and Akt phosphorylation with a concomitant increase of YB-1/HSP60 interaction. "	( Mechanism of YB-1-mediated translational induction of GluR2 mRNA in response to neural activity through nAChR. Kobayashi, S; Moue, M; Ohashi, S; Tanaka, T, 2012)	1.82
"Nicotine treatment also decreased AIMs by ~50% in wildtype mice, although not in α6⁻/⁻ mice."	( Role for α6 nicotinic receptors in l-dopa-induced dyskinesias in parkinsonian mice. Grady, SR; Hrachova, M; Huang, LZ; Mallela, A; McIntosh, JM; Park, KM; Quik, M, 2012)	1.1
"In nicotine-treated rats, blockade of β-adrenergic (propranolol), but not muscarinic (atropine), receptors caused additional reductions in reflex chronotropic responses, implying that nicotine selectively impairs reflex vagal activity."	( Estrogen provokes the depressant effect of chronic nicotine on vagally mediated reflex chronotropism in female rats. El-Gowelli, HM; El-Gowilly, SM; El-Mas, MM; Fouda, MA; Helmy, MM, 2012)	1.14
"Nicotine-treated adults displayed a robust aversion to an environment paired with a KOR agonist versus naïve adults. "	( Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner. Natividad, LA; O'Dell, LE; Orfila, JE; Tejeda, HA; Torres, OV, 2012)	2.07
"Nicotine replacement treatment (NRT) can be efficacious for smoking cessation, but used by only a minority of smokers in China. "	( Association of functional COMT Val108/Met polymorphism with smoking cessation in a nicotine replacement therapy. Cao, Y; Chen, D; Di, X; Guo, S; Kosten, T; Lu, L; Sun, H; Yang, F; Zhang, XY; Zou, Y, 2012)	2.05
"Nicotine treatment was associated with restoration of TLR2 and TLR9 responsiveness, and expansion of Tregs, including the CD4 1 CD25 2 FoxP3 1 phenotype."	( Nicotine treatment improves Toll-like receptor 2 and Toll-like receptor 9 responsiveness in active pulmonary sarcoidosis. Baughman, RP; Bhatt, NY; Cosmar, DG; Crouser, ED; Culver, DA; Huang, Q; Julian, MW; Schlesinger, LS; Shao, G; Wood, KL, 2013)	2.55
"Nicotine treatment in active pulmonary sarcoidosis was well tolerated and restored peripheral immune responsiveness to TLR2 and TLR9 agonists and expansion of FoxP3 1 Tregs, including a specific “preactivated” (CD25 2 ) phenotype. "	( Nicotine treatment improves Toll-like receptor 2 and Toll-like receptor 9 responsiveness in active pulmonary sarcoidosis. Baughman, RP; Bhatt, NY; Cosmar, DG; Crouser, ED; Culver, DA; Huang, Q; Julian, MW; Schlesinger, LS; Shao, G; Wood, KL, 2013)	3.28
"Nicotine-treated mice exhibited greater response accuracy during visual discrimination."	( Effects of chronic low- and high-dose nicotine on cognitive flexibility in C57BL/6J mice. Gould, TJ; Ortega, LA; Parikh, V; Tracy, BA, 2013)	1.38
"Nicotine replacement treatments are being alternatively applied as an aid to smoking cessation during pregnancy. "	( Evaluation of emotional behaviors in young offspring of C57BL/6J mice after gestational and/or perinatal exposure to nicotine in six different time-windows. Alkam, T; Aoyama, Y; Hiramatsu, M; Kim, HC; Mamiya, T; Nabeshima, T; Nitta, A; Yamada, K, 2013)	2.04
"Nicotine treatment induced epithelial-to-mesenchymal transition (EMT) in both cell lines by repressing E-cadherin expression, and led to the induction of stem cell markers Oct-4, Nanog, CD44 and BMI-1, which was reversed upon ectopic re-expression of E-cadherin."	( Nicotine promotes acquisition of stem cell and epithelial-to-mesenchymal properties in head and neck squamous cell carcinoma. Brumund, KT; Chen, J; Ellies, LG; Fan, JB; Haas, M; Kiang, A; Ongkeko, WM; Rahimy, E; Wang-Rodriguez, J; Weisman, RA; Yu, MA; Yu, V, 2012)	2.54
"Nicotine treatment led to declines in the striatal dopamine transporter, α6β2* nAChRs and various components of α6β2* and α4β2* nAChR-mediated release."	( The nicotine-mediated decline in l-dopa-induced dyskinesias is associated with a decrease in striatal dopamine release. Bordia, T; McIntosh, JM; Quik, M, 2013)	1.67
"Nicotine treatment selectively reversed the HRM-related phenotype in most brain areas and increased BDNF gene expression in cortex and hippocampus of both genotypes."	( Nicotine restores Wt-like levels of reelin and GAD67 gene expression in brain of heterozygous reeler mice. Fuso, A; Laviola, G; Romano, E, 2013)	2.55
"Nicotine treatment significantly increased the amount of mRNA for egr-1 and nur77 genes at 0.5 h post-nicotine treatment in the PC12 cells."	( Increase of transcriptional levels of egr-1 and nur77 genes due to both nicotine treatment and withdrawal in pheochromocytoma cells. Ichino, N; Ishiguro, H; Nagatsu, T; Nishii, K; Sawada, H; Yamada, K, 2002)	1.27
"Nicotine treatment resulted in necrosis and hyalinization of the nucleus pulposus in all rabbits. "	( Mechanism of intervertebral disc degeneration caused by nicotine in rabbits to explicate intervertebral disc disorders caused by smoking. Iwahashi, M; Matsuzaki, H; Tokuhashi, Y; Uematsu, Y; Wakabayashi, K, 2002)	2
"Nicotine treatment reduced food intake by up to 40% in lean and obese P."	( Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus. Cameron-Smith, D; Collier, GR; Fahey, R; Sanigorski, A, 2002)	2.48
"Nicotine treatment for smoking reduction had no detectable impact on smoking cessation."	( Nicotine replacement to reduce cigarette consumption in smokers who are unwilling to quit: a randomized trial. Etter, JF; Laszlo, E; Perneger, TV; Perrot, C; Zellweger, JP, 2002)	2.48
"Nicotine treatment triggers calcium influx into neuronal cells, which promotes cell survival in a number of neuronal cells. "	( Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells. Ikeuchi, T; Nakayama, H; Numakawa, T, 2002)	3.2
"Nicotine treatment significantly enhanced the constriction of the bone vasculature in response to NE, but not to AVP."	( Two week nicotine treatment selectively increases bone vascular constriction in response to norepinephrine. Feitelson, JB; Fleming, JT; Roberts, CS; Rowell, PP, 2003)	1.46
"Nicotine treatment had no effect on Smad2, but caused a down regulation of the PI-3 kinase pathway that may have contributed to inhibiting palatal fusion in vitro."	( Nicotine inhibits palatal fusion and modulates nicotinic receptors and the PI-3 kinase pathway in medial edge epithelia. Kang, P; Svoboda, KK, 2003)	3.2
"Nicotine treatment predominantly increased a receptor with characteristics of an alpha3beta2 subtype, whereas the NGF treatment exclusively increased a receptor with characteristics of an alpha3beta4 subtype."	( Differential regulation of nicotinic acetylcholine receptors in PC12 cells by nicotine and nerve growth factor. Ascarrunz, VS; Avila, AM; Dávila-García, MI; Kellar, KJ; Xiao, Y, 2003)	1.27
"Nicotine treatment did not increase the micronucleus frequencies in polychromatic erythrocytes while the positive control compound mitomycin C yielded the expected result."	( Nicotine is not clastogenic at doses of 1 or 2 mg/kg body weight given orally to male mice. Adler, ID; Attia, SM, 2003)	2.48
"Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. "	( Effects of nitric oxide on gastric ulceration induced by nicotine and cold-restraint stress. Liu, L; Mei, QB; Qui, BS; Tchou-Wong, KM, 2004)	2.01
"Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment."	( Effects of nitric oxide on gastric ulceration induced by nicotine and cold-restraint stress. Liu, L; Mei, QB; Qui, BS; Tchou-Wong, KM, 2004)	1.29
"nicotine treatment, three samples each) has increased from 0.974+/-0.017 to 0.995+/-0.002."	( Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells. Kane, J; Konu, O; Li, MD; Ma, JZ; Shi, SJ; Wang, J; Xu, X, 2004)	1.25
"Nicotine-treated embryos exhibited a 15% decrease in whole body weight and 7% decrease in brain weight at E16."	( Exposure to low concentrations of nicotine during cranial nerve development inhibits apoptosis and causes cellular hypertrophy in the ventral oculomotor nuclei of the chick embryo. Corbin Downey, L; Ewald, KW; Hatley, ME; Wielgus, JJ; Wilson, KC; Yeilding, RH, 2004)	1.32
"Nicotine patch pre-treatment before cessation did not reduce early withdrawal symptoms but increased sustained abstinence rates at 6 months. "	( Effect of pre-treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial. Bolliger, CT; Diacon, AH; Schuurmans, MM; van Biljon, X, 2004)	2.06
"Nicotine treatment significantly decreased errors in the task impaired schizophrenic group and this effect was most pronounced at the 6 mg level."	( Nicotine reduces antisaccade errors in task impaired schizophrenic subjects. Larrison-Faucher, AL; Matorin, AA; Sereno, AB, 2004)	2.49
"Nicotine treatment did not significantly change performance in the water maze at any age tested."	( Effects of early training and nicotine treatment on the performance of male NMRI mice in the water maze. Carrasco, MC; Redolat, R; Vicens, P, 2003)	1.33
"Nicotine treatment activates neuronal nicotinic acetylcholine receptors (nAChR) in peripheral and central nervous systems leading to depolarization and elevation of intracellular calcium levels, which are considered to cause stimulation of neurotransmitter release, synaptic transmission, intracellular signal transduction and gene expression."	( [Calcium signaling mediated by nicotine receptors in neurons]. Nakashima, T; Nakayama, H, 2004)	1.33
"Nicotine-treated animals had a significantly higher maximal efflux in cerebral cortex and superior colliculus, but not in thalamus or interpeduncular nucleus plus medial habenula."	( Binding and functional activity of nicotinic cholinergic receptors in selected rat brain regions are increased following long-term but not short-term nicotine treatment. Nguyen, HN; Perry, DC; Rasmussen, BA, 2004)	1.24
"Nicotine-treated rabbits had 78/440 (17.7%) positive/total swabs, and nicotine/placebo-treated rabbits had 149/792 (18.8%) positive/total swabs, whereas bupropion-treated rabbits had 23/440 (5.2%), and nicotine/bupropion-treated rabbits had 47/792 (5.9%) positive/total swabs."	( Bupropion (Zyban, Wellbutrin) inhibits nicotine-induced viral reactivation in herpes simplex virus type 1 latent rabbits. Azcuy, AM; Barker, SA; Hill, JM; Myles, ME; Nguyen, NT; Reisch, ER; Thompson, HW, 2004)	1.31
"Nicotine treated and control rats were trained in one trial learning step-through passive avoidance task, where retention latencies were carried out 1 h, 24 h, and 3 days after learning trial."	( Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement. Bahçekapili, N; Díler, AS; Tasyüreklí, M; Uzüm, G; Zíylan, YZ, 2004)	2.49
"Nicotine treatment increased dopamine transporter densities and decreased serotonin transporter densities in periadolescent rats."	( Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats. Collins, SL; Izenwasser, S; Ledon, J; Wade, D, 2004)	1.31
"Nicotine treatment on postnatal days (PN) 1-4 had little or no effect on alpha7 nAChRs but treatment during the second (PN11-14) or third (PN21-24) weeks elicited significant decrements in receptor expression in brainstem and cerebellum, regions containing cell bodies that project to the forebrain."	( Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos. Adam, SJ; Cousins, MM; Seidler, FJ; Slotkin, TA; Southard, MC, 2004)	1.26
"Nicotine-treated dams had lower body weights than control dams from gestational days 5-21, and the values reached statistical significance on gestational days 17, 20, and 21."	( Effects of maternal nicotine exposure on lung surfactant system in rats. Chen, CM; Wang, LF; Yeh, TF, 2005)	1.37
"Nicotine treatment of transfected cells produces dose- and time-dependent increases (up to approximately 100%) in numbers of I-Bgt binding sites."	( High-affinity epibatidine binding of functional, human alpha7-nicotinic acetylcholine receptors stably and heterologously expressed de novo in human SH-EP1 cells. Fryer, JD; George, AA; Groppi, VE; Hurst, RS; Leonard, SS; Lukas, RJ; Morrissy, S; Peng, JH; Schroeder, KM, 2005)	1.05
"Nicotine-treated endothelial cell (EC) conditioned media (CM) was shown to increase migration 20.3+/-l.l-fold."	( Nicotine induces mitogen-activated protein kinase dependent vascular smooth muscle cell migration. Chen, A; Dhadwal, AK; Di Luozzo, G; Pradhan, S; Sumpio, BE; Ueno, H, 2005)	2.49
"Nicotine treatment of the Cpn-infected cells up-regulated IL-10, but not TNF-alpha and IL-12, and also resulted in significant down-regulation of TGF-beta1 production which was marked in the Cpn-infected control cells."	( Nicotine modulates cytokine production by Chlamydia pneumoniae infected human peripheral blood cells. Friedman, H; Hakki, A; Klein, TW; Mamata, Y; Newton, C; Pross, S; Yamamoto, Y, 2005)	2.49
"Nicotine treatment increased T2 values, with a significant effect in the cingulate cortex."	( Sub-chronic nicotine-induced changes in regional cerebral blood volume and transversal relaxation time patterns in the rat: a magnetic resonance study. Calderan, L; Chiamulera, C; Fabene, PF; Fumagalli, GF; Marzola, P; Sbarbati, A, 2005)	1.43
"Nicotine treatment exhibits several features of apoptosis in mouse Leydig cells."	( Nicotine induces apoptosis in TM3 mouse Leydig cells. Jang, MH; Joo, KJ; Kim, CJ; Kim, KH; Kwon, CH; Park, HJ, 2005)	2.49
"Nicotine treatment resulted in significantly decreased expression of lipogenic and increased expression of myogenic markers in a dose-dependent manner, indicating nicotine-induced LIF-to-MYF transdifferentiation."	( Mechanism of nicotine-induced pulmonary fibroblast transdifferentiation. Chen, X; Khazanchi, A; Rehan, VK; Romero, S; Santos, J; Sugano, S; Torday, JS; Wang, Y, 2005)	1.42
"Nicotine treatment down-regulated TGF-beta1-induced p38 MAPK phosphorylation."	( Nicotine inhibits myofibroblast differentiation in human gingival fibroblasts. Fang, Y; Svoboda, KK, 2005)	2.49
"Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of "stimulated" on the visual analog scales, and scores on the Amphetamine scale of the ARCI."	( Transdermal nicotine alters some of marihuana's effects in male and female volunteers. Gross, MM; Kouri, EM; Lukas, SE; McCarthy, EM; Penetar, DM; Peters, EN; Rhee, CK, 2005)	1.43
"Nicotine treatment increased p21 expression in immortalized cells (HaCaT, IHOK) and oral cancer cells (HN4, HN12), but decreased pRb and p53 expression in oral cancer cells."	( Effects of nicotine on proliferation, cell cycle, and differentiation in immortalized and malignant oral keratinocytes. Guo, HY; Jeon, BH; Jun, CD; Kim, EC; Lee, HJ; Lee, SK; Park, MH, 2005)	1.44
"In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed."	( Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats. Kalpana, C; Menon, VP; Rajasekharan, KN, 2005)	1.06
"The nicotine-treated rats were less sensitive to the threshold elevating effects of D1-like receptor antagonism."	( Decreased sensitivity to the effects of dopamine D1-like, but not D2-like, receptor antagonism in the posterior hypothalamic region/anterior ventral tegmental area on brain reward function during chronic exposure to nicotine in rats. Bruijnzeel, AW; Markou, A, 2005)	1
"Nicotine treatment prevents chronic psychosocial stress-induced impairment of hippocampus-dependent spatial memory and long-term potentiation (LTP). "	( Nicotine prevents stress-induced enhancement of long-term depression in hippocampal area CA1: electrophysiological and molecular studies. Aleisa, AM; Alkadhi, KA; Alzoubi, KH, 2006)	3.22
"Nicotine treatment, which can improve working memory, eliminated the impairment associated with the deletion of the MT-1 and MT-2 genes in a dose-related fashion after acquisition training in the aging adult mice."	( Metallothionein expression and neurocognitive function in mice. Freedman, JH; Levin, ED; Perraut, C; Pollard, N, 2006)	1.06
"Nicotine treatment of uninfected ARPE-19 cells had no effect on baseline NF-kappaB levels."	( Nicotine treatment alters NF-kappaB expression in human cytomegalovirus-infected ARPE-19 cells. Buckner, AE; Dix, RD, 2006)	2.5
"Nicotine treatment decreases the intracellular copper concentration and attenuates Abeta-mediated neurotoxicity facilitated by the addition of copper, and these effects are independent of the activation of nicotinic acetylcholine-receptor."	( Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis. Chen, Q; He, W; Huang, YY; Li, FL; Liu, NQ; Liu, Q; Lu, ZB; Qin, C; Zhang, J; Zhao, BL; Zhu, H, 2006)	2.5
"Nicotine treatment alone enhanced synaptic plasticity by lowering the threshold for long-term depression (LTD) in the corticostriatal pathway."	( Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. Chen, L; Langston, JW; McCallum, SE; Parameswaran, N; Quik, M; Xie, X, 2006)	1.42
"Nicotine treatment reversed established stress-induced impairment of LTP."	( Chronic but not acute nicotine treatment reverses stress-induced impairment of LTP in anesthetized rats. Aleisa, AM; Alkadhi, KA; Alzoubi, KH, 2006)	1.37
"Nicotine treated animals had lower percentage of viability areas (60.7% +/- 6.8) than the control group (73.7% +/- 9.5), p=0.016. "	( Buflomedil and pentoxifylline in the viability of dorsal cutaneous flaps of rats treated with nicotine. de Tolosa, EM; Mauad, RJ; Mauad, T; Shimizu, MH, 2006)	2
"Nicotine treatment increased alpha4beta2* nAChRs by > or =50% in striatum of both unlesioned and lesioned animals."	( Partial recovery of striatal nicotinic receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys with chronic oral nicotine. Bordia, T; Fan, H; Langston, JW; McIntosh, JM; Parameswaran, N; Quik, M, 2006)	1.26
"Nicotine treatment was found to be effective in attenuating the attentional and memory impairments caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of the cognitive impairment of schizophrenia."	( Nicotinic-antipsychotic drug interactions and cognitive function. Levin, ED; Rezvani, AH, 2006)	1.06
"Nicotine-treated rats exhibited greater discrimination between the two trial types as evidenced by less frequent responding during non-reinforced trials, and learned the discrimination in fewer sessions than vehicle-treated rats."	( Nicotine administration enhances conditioned inhibition in rats. Bucci, DJ; MacLeod, JE; Potter, AS; Simoni, MK, 2006)	2.5
"Nicotine treatment at 100 mg/l for 3 min by immersion before testing caused a significant decrease in diving throughout the session, while 50 mg/l was effective during the first minute when the greatest bottom dwelling was seen in controls."	( Anxiolytic effects of nicotine in zebrafish. Bencan, Z; Cerutti, DT; Levin, ED, 2007)	1.38
"Nicotine treatment caused expression of MMP-1, 2, 3, and 13, but not MMP-14, to increase significantly after 5 or 10 d of culture; MMP-14 expression did not change through day 14."	( Nicotine treatment induces expression of matrix metalloproteinases in human osteoblastic Saos-2 cells. Katono, T; Kawato, T; Maeno, M; Motohashi, M; Oka, H; Suzuki, N; Tanabe, N; Yamanaka, K, 2006)	2.5
"Nicotine treatment increased the number of EPCs in the bone marrow and spleen, and increased their incorporation into the vasculature of ischemic tissue. "	( Endothelial progenitor cells participate in nicotine-mediated angiogenesis. Aicher, A; Chang, E; Cooke, JP; Heeschen, C, 2006)	2.04
"Nicotine treatment significantly decreased the endogenous antioxidant status viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), GSH, vitamin A, E and C."	( Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with N-acetylcysteine. Kalpana, C; Menon, VP; Muthukumaran, S; Srinivasan, M; Sudheer, AR, 2007)	1.33
"Nicotine treatment caused dose-dependent activation of extracellular signal-regulated kinases (ERK1/2), the maxima occurring at 100 micro m and at 3 min after treatment; the response was suppressed by the ERK1/2 inhibitor. "	( Nicotine-induced proliferation of isolated rat pancreatic acinar cells: effect on cell signalling and function. Bose, C; Chowdhury, P; Udupa, KB, 2007)	3.23
"Nicotine treatment significantly altered the abundance of 41, 29, 54, and 14 ventral tegmental transcripts in strains C57BL/6ByJ, BALB/cJ, B6.Cb4i5-alpha4/Vad, and B6.Ib5i7-beta25A/Vad, respectively."	( Ventral tegmental transcriptome response to intermittent nicotine treatment and withdrawal in BALB/cJ, C57BL/6ByJ, and quasi-congenic RQI mice. Chakraborty, G; Morahan, G; O'Brien, D; Saito, M; Vadasz, C; Wang, R; Zavadil, J, 2007)	1.31
"The nicotine treated group had a mean +/- SEM adhesion score of 2.4 +/- 0.2, which was significantly greater than that of the control group (1.2 +/- 0.2) (P < 0.05, Mann Whitney U test.). "	( Evaluation of postoperative peritoneal adhesion formation following perioperative nicotine administration. Aherne, NJ; Cahill, RA; Condon, ET; O'malley, DB; Redmond, HP, 2007)	1.12
"Nicotine treatment significantly reduced the rate of cleavage and blastocyst development after parthenogenetic activation."	( Nicotine alters bovine oocyte meiosis and affects subsequent embryonic development. Aston, KI; Bunch, TD; Li, GP; Liu, Y; Rickords, LF; Sessions, BR; White, KL, 2007)	2.5
"Nicotine treatment resulted in TIMP-2 redistribution to the cell surface."	( Nicotine increases the collagen-degrading ability of human gingival fibroblasts. Olson, BL; Windsor, LJ; Zhou, J, 2007)	2.5
"Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice."	( Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway. Barvais, L; Claessen, N; Diallo, B; Florquin, S; Goldman, M; Kubjak, C; Le Moine, A; Loi, P; Moore, F; Sadis, C; Stokman, G; Teske, G, 2007)	2.5
"Nicotine pretreatment considerably decreased microglial activation with significant reduction of tumour necrosis factor (TNF)-alpha mRNA expression and TNF-alpha release induced by LPS stimulation."	( Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. Ahn, YW; Choi, YJ; Chung, ES; Jin, BK; Lee, DY; Lee, G; Lee, PH; Park, HJ, 2007)	1.36
"The nicotine treatment significantly decreased neurotensin-like immunoreactivity content in the ventral tegmental area, as well as related regions such as prefrontal cortex, substantia nigra, and anterior striatal region 12-18 h after drug treatment, but not the nucleus accumbens."	( Nicotinic and dopamine D2 receptors mediate nicotine-induced changes in ventral tegmental area neurotensin system. Alburges, ME; Hanson, GR; Hoonakker, AJ, 2007)	1.08
"Nicotine treatments from 15 min to 5h did not cause any changes in the expression and localization of principal junctional proteins."	( Effect of nicotine and polyaromtic hydrocarbons on cerebral endothelial cells. Buzás, K; Deli, MA; Farkas, AE; Hunyadi-Gulyás, E; Hutamekalin, P; Krizbai, IA; Medzihradszky, KF; Meksuriyen, D; Nagyoszi, P; Orbók, A; Veszelka, S; Wilhelm, I, 2008)	1.47
"Nicotine treatment resulted in a rapid and transient decrease in food-intake and a moderate decrease in maternal body weight gain."	( Prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion injury in adult offspring. Lawrence, J; Rejali, M; Xiao, D; Xue, Q; Yang, S; Zhang, L, 2008)	1.48
"Nicotine pretreatment reduced peak and total levodopa-induced dyskinesias in levodopa-naive monkeys over an 8-week period, with a decrease in total dyskinesias of about 50%. "	( Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys. Cox, H; Di Monte, D; Langston, JW; O'Leary, K; Parameswaran, N; Quik, M, 2007)	3.23
"The nicotine-treated rats had less (49%) elongation than the placebo-treated controls (P=0.0008)."	( Nicotine impairs distraction osteogenesis in the rat mandible. Glowacki, J; Kaban, LB; Perrott, D; Schulten, AJ, 2008)	2.27
"Nicotine treatment did not change pain report or morphine use in either anesthetic group (P > 0.05)."	( Anesthesia matters: patients anesthetized with propofol have less postoperative pain than those anesthetized with isoflurane. Cheng, SS; Flood, P; Yeh, J, 2008)	1.07
"The nicotine treatment was found to significantly enhance precursor cell proliferation in the SVZ."	( Nicotine-induced fibroblast growth factor-2 restores the age-related decline of precursor cell proliferation in the subventricular zone of rat brain. Belluardo, N; Bonomo, A; Di Liberto, V; Frinchi, M; Fuxe, K; Mudo', G, 2008)	2.27
"Nicotine or caffeine-treated animals showed significant restoration against most of the MPTP-induced alterations."	( Nicotine and caffeine-mediated modulation in the expression of toxicant responsive genes and vesicular monoamine transporter-2 in 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease phenotype in mouse. Nath, C; Patel, DK; Patel, S; Singh, C; Singh, K; Singh, MP; Singh, S, 2008)	2.51
"Nicotine-treated adults developed a CPA to the mecamylamine-associated compartment and expressed significant physical withdrawal signs, whereas similarly treated adolescents did not. "	( Interactions between age and the aversive effects of nicotine withdrawal under mecamylamine-precipitated and spontaneous conditions in male Wistar rats. Lê, AD; Li, Z; Shram, MJ; Siu, EC; Tyndale, RF, 2008)	2.04
"Nicotine treatment modulates both dopaminergic and glutamatergic neurotransmission, and these effects are specific both to brain region and functional system."	( [A review of the effects of nicotine on schizophrenia]. Bidzan, L, )	1.15
"In nicotine-treated groups, fetal developmental parameters including body weight were significantly lower."	( Growth retardation of fetal rats exposed to nicotine in utero: possible involvement of CYP1A1, CYP2E1, and P-glycoprotein. Chen, M; Pan, XL; Wang, H; Wang, T; Xiao, FQ; Yan, YE, 2009)	1.13
"The nicotine-treated mice developed conditioned place preference after being conditioned twice with morphine 5 mg/kg s.c."	( Morphine-nicotine interaction in conditioned place preference in mice after chronic nicotine exposure. Ahtee, L; Korpi, ER; Piltonen, M; Tuominen, RK; Vihavainen, T, 2008)	1.24
"The nicotine treatment induced a significant depletion of amine stores and an increase of amine turnover in dopamine (DA) and noradrenaline (NA) nerve terminals of the median eminence and of the peri- and paraventricular and dorsomedial NA systems of the hypothalamus using the tyrosine hydroxylase (TH) inhibition model."	( Differential effects of mecamylamine on the nicotine induced changes in amine levels and turnover in hypothalamic dopamine and noradrenaline nerve terminal systems and in the secretion of adenohypophyseal hormones in the castrated female rat. Evidence for Agnati, LF; Anderson, K; Eneroth, P; Fuxe, K, 1984)	1.01
"In nicotine-treated rats, complete adaptation did not occur and the plasma corticosterone showed a significant (P less than 0.05) negative correlation with hippocampal 5-HT."	( Effects of chronic nicotine administration on the response and adaptation to stress. Balfour, DJ; Benwell, ME, 1982)	1.11
"The nicotine treatment produced a significant depletion of CA stores and an increase of CA turnover in DA and NA nerve terminals of the median eminence and in peri- and paraventricular NA systems."	( Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerve terminal systems and of prolactin, LH, FSH and TSH secretion in the castrated male rat. Agnati, LF; Andersson, K; Eneroth, P; Fuxe, K, 1982)	1.04
"Nicotine treated rats were not simply seeking calories provided by the EtOH solution, since nicotine treatment did not enhance intake of a distinctively flavored solution isocaloric to 10% ethanol."	( Ethanol intake increases during continuous administration of amphetamine and nicotine, but not several other drugs. Ellison, G; Nelson, L; Potthoff, AD, 1983)	1.22
"Nicotine treatment of normal male rats and of ovariectomized female rats results in increases of dopamine (DA), noradrenaline (NA) and adrenaline (A) turnover in the hypothalamus, especially within the median eminence. "	( Mecamylamine induced blockade of nicotine induced inhibition of gonadotrophin and TSH secretion and of nicotine induced increases of catecholamine turnover in the rat hypothalamus. Agnati, LF; Andersson, K; Eneroth, P; Fuxe, K; Gustafsson, JA, 1980)	1.99
"The nicotine-treated offspring showed reduced spontaneous alternation both as neonates and adults."	( Behavioral effects of prenatal exposure to nicotine in guinea pigs. Becker, RF; Johns, JM; Louis, TM; Means, LW, )	0.87
"Nicotine-treated rabbits were compared with control rabbits (10) in terms of blood serum biochemistry and lipid profiles, blood cells counts, changes in aortic endothelial cell morphologic characteristic and distribution, and vessel wall permeability (Evans blue dye uptake)."	( Effects of chronic oral consumption of nicotine on the rabbit aortic endothelium. Booyse, FM; Osikowicz, G; Quarfoot, AJ, 1981)	1.25
"Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period."	( Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits. Cho, CH; Ho, J; Luk, CT; Luk, IS; Wong, WM; Yuen, ST, 1994)	1.33
"In nicotine-treated rats compared with placebo-treated controls, acetylcholine-evoked axon reflex flare was enhanced by 240% (p < 0.01) without enhancement of electrically evoked flare."	( The role of skin nociceptive afferent nerves in blister healing. Carr, RW; Delaney, CA; Morris, MJ; Roberts, RG; Westerman, RA, 1993)	0.8
"Nicotine treatment did not affect plasma and liver zinc and copper concentrations or liver manganese (Mn) concentrations."	( Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Bui, LM; Dubick, MA; Keen, CL, 1995)	1.3
"Nicotine treatment of cardiac fibroblasts also led to decreased collagenase activity (62%, P < 0.001) in the conditioned medium of those cells in culture."	( Nicotine regulates collagen gene expression, collagenase activity, and DNA synthesis in cultured cardiac fibroblasts. Eghbali-Webb, M; Rimar, S; Tomek, RJ, 1994)	2.45
"The nicotine treatment (10(-5), 10(-4) and 10(-3) mol/L) did not cause any effects on the process of wound repair."	( Effect of nicotine in migration and proliferation of rabbit gastric mucosal cells in a culture cell model. Hirose, M; Kitami, N; Kobayashi, O; Maehiro, K; Murai, T; Nagahara, A; Ogihara, T; Sato, N; Wang, XE; Watanabe, S, 1994)	1.17
"Nicotine treatment and copper (Cu) deficiency have been associated with an increased production of reactive oxygen species that may contribute to the development and/or progression of cardiovascular diseases (CVD). "	( Influence of 12-week nicotine treatment and dietary copper on blood pressure and indices of the antioxidant system in male spontaneous hypertensive rats. Bui, LM; Dubick, MA; Keen, CL, )	1.89
"Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms."	( Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Feyerabend, C; Gustavsson, G; Russell, MA; Sawe, U; Stapleton, JA; Wiseman, D; Wiseman, SM, 1995)	1.24
"Nicotine treatment for 1-2 days increased both the TH and DBH mRNA levels."	( Nicotine increases expression of tyrosine hydroxylase gene. Involvement of protein kinase A-mediated pathway. Hiremagalur, B; Nankova, B; Nitahara, J; Sabban, EL; Zeman, R, 1993)	2.45
"This nicotine treatment also induced a 1.6-fold increase in skin flap tissue content of norepinephrine compared with the saline-treated control."	( Evidence for nicotine-induced skin flap ischemic necrosis in the pig. Forrest, CR; Pang, CY; Xu, N, 1994)	1.11
"Nicotine pretreatment did not affect the release evoked by amphetamine, veratridine, or 15 mM K+."	( Characterization of nicotine-induced desensitization of evoked dopamine release from rat striatal synaptosomes. Hillebrand, JA; Rowell, PP, 1994)	1.33
"The nicotine pretreatment also inhibited the reserpine-induced hypothermia and decrease in the locomotor activity."	( Possible explanations for the antagonism by nicotine against reserpine-induced depletion of monoamines in mouse brain. Furuno, K; Gomita, Y; Oishi, R; Saeki, K; Suemaru, K, 1993)	1.03
"Nicotine treatment restored performance of the lesioned rats to control levels."	( Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection. Briggs, SJ; Christopher, NC; Levin, ED; Rose, JE, 1993)	1.44
"The nicotine replacement treatment lasted for 3 months and was carried out according to the manufacturers recommendations."	( Transdermal nicotine in smoking cessation and involvement of non-specific influences. Huber, T; Keller-Stanislawski, B; Merz, PG; Rietbrock, N; Woodcock, BG, 1993)	1.15
"Nicotine treatment also prevented the stimulatory effect of naltrexone on serum LH concentrations."	( Naltrexone treatment attenuates the inhibitory effect of nicotine treatment on serum LH in rats. Burden, HW; Davenport, A; Hodson, CA; Price, G, 1993)	1.25
"Nicotine treatment weakly decreased serum levels of aldosterone at 2 h, possibly as a consequence of nicotine metabolising to cotinine, resulting in higher serum levels of cotinine than nicotine."	( Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in the normal male rat. Andersson, K; Eneroth, P; Jansson, A; Kuylenstierna, F, 1993)	2.45
"Nicotine pretreatment of similar aged rats markedly improved overall learning and the rate of learning compared to aged controls."	( Nicotine enhances the learning and memory of aged rats. Arendash, GW; Sanberg, PR; Sengstock, GJ, 1995)	2.46
"Nicotine pretreatment significantly enhanced this effect in the PFC, whereas it did not affect the response in the NAC."	( Condition-independent sensitization of locomotor stimulation and mesocortical dopamine release following chronic nicotine treatment in the rat. Hertel, P; Nisell, M; Nomikos, GG; Panagis, G; Svensson, TH, 1996)	1.23
"Nicotine pre-treatment (10(-9)-10(-7) M) dose-dependently attenuated dexamethasone potentiation of kainic acid-induced neurotoxicity."	( Nicotine protects against the dexamethasone potentiation of kainic acid-induced neurotoxicity in cultured hippocampal neurons. Kito, S; Miyoshi, R; Semba, J, 1996)	2.46
"Nicotine patch treatment diminished the physiologic and performance changes, but subjective measures of tobacco abstinence (cigarette craving, increases in withdrawal scores) were not significantly reduced."	( Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal. Butschky, MF; Fant, RV; Henningfield, JE; Pickworth, WB, 1996)	1.33
"Nicotine pretreatment reduced ANG II inhibition of LTP induction in a dose-dependent manner."	( Nicotine blocks angiotensin II inhibition of LTP in the dentate gyrus. Armstrong, DL; Phelix, CF; Wayner, MJ, 1996)	2.46
"Nicotine treatment resulted in 35-40% (p < 0.001) decrease in the blood flow in the periphery of the ischemic core during reperfusion, an increase in the neurologic score of 2.6-fold (p < 0.01), and 36% (p < 0.05) and 121% (p < 0.01) increases in the injury and edema volume in the pallium, respectively."	( Chronic nicotine treatment enhances focal ischemic brain injury and depletes free pool of brain microvascular tissue plasminogen activator in rats. Kittaka, M; Schreiber, SS; Sun, N; Wang, L; Zlokovic, BV, 1997)	1.45
"Nicotine treatment upregulated the expression of TH, PNMT, and NPY genes in a dose-dependent fashion."	( Expression of catecholamine-synthesizing enzymes, peptidylglycine alpha-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine. Houpt, TA; Jahng, JW; Joh, TH; Wessel, TC, 1997)	1.21
"Nicotine antagonist treatment also reduces responding, although human studies usually find a transient increase in smoking, which is interpreted as an attempt to compensate for nicotinic receptor blockade."	( Nicotine self-administration in animals and humans: similarities and differences. Corrigall, WA; Rose, JE, 1997)	2.46
"Such nicotine treatment did not influence the reduction in TH-IR cell bodies in the locus ceruleus following 15-20 min of perinatal asphyxia."	( Perinatal asphyxia-induced changes in rat brain tyrosine hydroxylase-immunoreactive cell body number: effects of nicotine treatment. Andersson, K; Bjelke, B; Blum, M; Chen, Y; Gross, J; Herrera-Marschitz, M, 1997)	0.96
"Nicotine treatment (12 mg/kg/d) alone did not affect serum gastrin levels; however, nicotine potentiated the hypergastrinemic action of famotidine."	( Interaction of nicotine and a H2-receptor antagonist, famotidine, on gastrin and chromogranin A expression. Gomez, G; Greeley, GH; Udupi, V, 1997)	1.37
"Nicotine treatment blocked naloxone induced LH release and reduced LHRH induced increases in serum LH."	( Effect of prior nicotine treatment on drug induced changes in serum LH concentrations in rats. Burden, HW; Davis, MC; Hodson, CA, 1997)	1.36
"Nicotine-pretreated rats exhibited higher levels of activity following a nicotine challenge."	( Behavioural and biochemical adaptations to nicotine in rats: influence of MK801, an NMDA receptor antagonist. Goldberg, SR; Pauly, JR; Schindler, CW; Shoaib, M, 1997)	1.28
"Nicotine treatment also decreased that for 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]-5,11-dihydro-6H-pyrido [2,3-b] [1,4] benzodiazepin-6-one (AF-DX 116) (M2-subtype) by 77% in cerebellum on postnatal 14th day."	( Nicotine administration decreases the number of binding sites and mRNA of M1 and M2 muscarinic receptors in specific brain regions of rat neonates. Konishi, Y; Mayumi, M; Muramatsu, I; Taniguchi, T; Zhu, J, 1998)	2.46
"Nicotine (NT) treatment impairs T-cell receptor (TCR)-mediated signaling, leading to the arrest of T cells in the G1 phase of the cell cycle and inhibition of the antibody plaque-forming cell (AFC) response to sheep red blood cells (SRBC). "	( Effect of nicotine on the immune system: possible regulation of immune responses by central and peripheral mechanisms. Geng, Y; Kluger, MJ; Kozak, W; Perryman, EK; Savage, SM; Snow, GE; Sopori, ML; Soszynski, D, 1998)	2.15
"Nicotine pretreatment augmented the vasodilatory response to dopamine at doses falling within the mid range of the dopamine dose-response relationship, and this augmentation was blocked by the nicotinic ganglionic receptor antagonist mecamylamine."	( Acute nicotine pretreatment augments dopaminergic pulmonary vasodilation. Russ, RD, 1998)	1.5
"Nicotine pretreatment did not influence the increase in DA overflow into dialysis probes, located in the core of the NAcc, evoked by systemic injections of D-amphetamine or cocaine (15 mg/kg i.p.) but decreased the overflow evoked by the administration of D-amphetamine (1 x 10(-6) M) through the dialysis probe."	( The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to D-amphetamine. Balfour, DJ; Birrell, CE, 1998)	1.36
"Nicotine treatment significantly raised cAMP levels."	( Differing temporal roles of Ca2+ and cAMP in nicotine-elicited elevation of tyrosine hydroxylase mRNA. Gueorguiev, VD; Hiremagalur, B; Menezes, A; Sabban, EL; Zeman, RJ, 1999)	1.28
"Nicotine-treated rats developed significantly enlarged left ventricles with thin, infarcted walls and a rightward shift in the passive pressure-volume relationship."	( Nicotine-modified postinfarction left ventricular remodeling. Hong, D; Omens, J; Villarreal, FJ, 1999)	2.47
"Nicotine treatment for as long as 3 months did not have any significant effect on these 'stopping smoking changes'."	( Effects of nicotine nasal spray on atherogenic and thrombogenic factors during smoking cessation. Blöndal, T; Franzon, M; Gudmundsson, TV; Lúdvíksdóttir, D; Säwe, U, 1999)	1.41
"Nicotine replacement treatment use, ratings of withdrawal symptoms, ratings of product characteristics and helpfulness, and biochemically validated continuous lapse-free abstinence."	( Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Burrows, S; Foulds, J; Hajek, P; Meadow, A; Nilsson, F; West, R, 1999)	2.03
"Nicotine pretreatment attenuated some of these changes in a region- and time-dependent manner."	( Differential effects of nicotine against stress-induced changes in dopaminergic system in rat striatum and hippocampus. Ihara, H; Nagai, N; Pawlak, R; Takada, A; Takada, Y; Takahashi, H; Urano, T, 2000)	1.34
"Nicotine-treated rats receiving mecamylamine or i.c.v."	( Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. Koob, GF; Markou, A; Stinus, L; Watkins, SS, 2000)	1.29
"Nicotine treatment increases intracellular free Ca(2+) concentration [Ca(2+)](i), stimulates catecholamine release, and elevates gene expression for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). "	( Involvement of alpha7 nicotinic acetylcholine receptors in activation of tyrosine hydroxylase and dopamine beta-hydroxylase gene expression in PC12 cells. Gueorguiev, VD; Meyer, EM; Sabban, EL; Zeman, RJ, 2000)	1.75
"In nicotine-untreated neonates, [3H]HC-3 binding sites of cerebral cortex increased from 64 fmol/mg protein at postnatal day 7 to 142 fmol/mg protein at postnatal day 35."	( Effects of perinatal nicotine exposure on development of [3H]hemicholinium-3 binding sites in rat neonate brain. Muramatsu, I; Suzuki, F; Tanaka, T; Taniguchi, T; Zhu, J, 2000)	1.14
"Nicotine patch (TNS) treatment was provided for 8 weeks; paroxetine or placebo was provided for 9 weeks."	( Nicotine patch and paroxetine for smoking cessation. Fortmann, SP; Hayward, C; Killen, JD; Rothman, M; Schatzberg, AF; Strausberg, L; Sussman, L; Varady, A, 2000)	2.47
"Nicotine treatment did not affect the performance of rats that were more active in that environment."	( Nicotine enhances acquisition of a T-maze visual discrimination: assessment of individual differences. Besheer, J; Bevins, RA, 2000)	2.47
"Nicotine pretreatment markedly attenuated all these effects."	( Nicotine protects against arachidonic-acid-induced caspase activation, cytochrome c release and apoptosis of cultured spinal cord neurons. Garrido, R; Hennig, B; Mattson, MP; Toborek, M, 2001)	2.47
"Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women."	( The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment. Fonte, C; Meeker, J; Perkins, KA; White, W; Wilson, A, 2001)	1.28
"Nicotine treatment also significantly increased jejunal segmental weight."	( Dual effect of chronic nicotine administration: augmentation of jejunitis and amelioration of colitis induced by iodoacetamide in rats. Cohen, P; Eliakim, R; Heyman, SN; Karmeli, F; Rachmilewitz, D, 2001)	1.34
"Nicotine pretreatment attenuated cocaine-induced increases in reports of "high" and "stimulated" and increased the latency to detect cocaine effects and cocaine-induced euphoria."	( Nicotine alters some of cocaine's subjective effects in the absence of physiological or pharmacokinetic changes. Kouri, EM; Lukas, SE; Stull, M, )	2.3
"Nicotine treatment significantly delayed the onset of hematopoietic foci and reduced their size."	( Correlation between nicotine-induced inhibition of hematopoiesis and decreased CD44 expression on bone marrow stromal cells. Khaldoyanidi, S; Kozlov, V; Matrosova, V; Orlovskaya, I; Sikora, L; Sriramarao, P, 2001)	1.36
"Nicotine treatment (1 mg/kg) produced significant improvement in both paradigms in corticosterone-treated mice."	( Chronic corticosterone treatment alters sensory gating in C3H mice. Bullock, AE; Collins, AC; Stevens, KE, )	0.85
"The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking."	( The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments. Franzon, MA; Lunell, E; Olmstead, RE; Schneider, NG, 2001)	1.35
"Nicotine-induced treatment differences were not detected in serum calcium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D."	( Effects of nicotine on bone mass, turnover, and strength in adult female rats. Akhter, MP; Cullen, DM; Fung, YK; Haven, MC; Haynatzki, GR; Iwaniec, UT; Nespor, S, 2001)	1.42
"The nicotine treatment of MH-S alveolar macrophages after infection with L."	( Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. Friedman, H; Klein, TW; Matsunaga, K; Yamamoto, Y, 2001)	0.98
"Nicotine pretreatment significantly reduced one of the three measures of compulsive checking behavior."	( Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder. Culver, KE; Louis, VA; Szechtman, H; Taylor, CT; Tizabi, Y; Waxman, D, 2002)	1.44
"Nicotine treatment reduced the hyperglycemia and incidence of disease in both the MLDS and NOD mouse models of diabetes."	( Nicotine reduces the incidence of type I diabetes in mice. Mabley, JG; Pacher, P; Salzman, AL; Southan, GJ; Szabó, C, 2002)	2.48
"Nicotine treatment increased NO metabolites significantly in all brain regions compared with naïve or saline-treated rats."	( Effects of chronic nicotine administration on nitric oxide synthase expression and activity in rat brain. Alonso, JR; Balkan, B; Koylu, EO; Pogun, S; Weruaga, E, 2002)	1.36
"The nicotine-treated groups were injected with nicotine."	( Nicotine administration decreases nitric oxide synthase expression in the hypothalamus of food-deprived rats. Choue, RW; Chung, JH; Jang, MH; Kang, HS; Kang, SA; Kim, CJ; Kim, EH; Lim, BV; Shin, MC, 2002)	2.24
"Nicotine treatment was found to raise plasma free fatty acids by similar amounts in both lean and obese mice."	( Acute effects of nicotine on plasma free fatty acid concentrations and on the response to cold stress, in lean and obese (genotype ob/ob) mice. Batt, RA; Topping, DL, 1979)	1.32
"Nicotine-treated animals also had elevated CCS levels 2 weeks after the last chronic injection."	( Tolerance to nicotine following chronic treatment by injections: a potential role for corticosterone. Collins, AC; Grun, EU; Pauly, JR, 1992)	1.37
"The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy."	( Persistence of chronic nicotine-induced cognitive facilitation. Briggs, SJ; Christopher, NC; Levin, ED; Rose, JE, 1992)	1.08
"Nicotine treatment resulted in an increase in the pro-opiomelanocortin mRNA levels in the anterior pituitary and in a decrease in the intermediate pituitary, but did not change the levels of pro-opiomelanocortin mRNA in the hypothalamus."	( Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and alpha 3 nicotinic receptor subunit in the rat. Höllt, V; Horn, G, )	1.26
"Nicotine treatment increases striatal and cortical hemicholinium-3 binding at all three ages, with greater percent increases at day 5."	( High-affinity choline transport regulation by drug administration during postnatal development. Happe, HK; Murrin, LC, 1992)	1
"2. Nicotine pretreatment failed to alter the deficit in locomotor activity and the reduction in striatal levels of dopamine produced by MPTP."	( Chronic administration of nicotine fails to alter the MPTP-induced neurotoxicity in mice. Fiske, LA; Fung, YK; Lau, YS, 1991)	1.1
"Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment than both placebo- and control-subjects: 69% in the nicotine condition, 51.2% and 44.4% under placebo and control conditions respectively."	( Combination of behavioral smoking cessation with transdermal nicotine substitution. Bents, H; Buchkremer, G; Horstmann, M; Opitz, K; Tölle, R, 1989)	1.24
"The nicotine treatment did not affect the apomorphine-induced locomotor activity, however, the (+)-amphetamine-stimulated locomotor activity was attenuated."	( Acute effect of nicotine on the striatal dopaminergic system in the rat. Fung, YK; Lau, YS, 1986)	1.1
"Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels."	( Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male rat. Agnati, LF; Andersson, K; Eneroth, P; Fuxe, K; Härfstrand, A, 1988)	1.26
"The nicotine treatment led to increases in the specific binding of both [3H]prazosin and [3H]clonidine in the cerebral cortex."	( Alteration of alpha and muscarinic receptors in rat brain and heart following chronic nicotine treatment. Muramatsu, I; Oshita, M; Yamanaka, K, 1985)	0.97
"Nicotine-treatment also caused a decrease in the Bmax of cortical (3H)DHA binding comparable to the case of stress, and increased the (3H)clonidine binding."	( Effect of chronic nicotine treatment against repeated immobilization stress. Kigoshi, S; Muramatsu, I; Yamanaka, K, 1987)	1.33
"Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment as well as during the follow-up period, than both placebo- and control-subjects."	( [Long-term effects of a combination of transdermal nicotine administration with behavior therapy for smoking cessation]. Bents, H; Buchkremer, G; Minneker, E; Opitz, K, 1988)	1.25
"Nicotine treated and untreated cells released minimal amounts of prostaglandin E2."	( The effect of nicotine on human endothelial cell release of prostaglandins and ultrastructure. Bull, HA; Machin, SJ; Pittilo, RM; Woolf, N, 1988)	1.36
"Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water."	( The effects of long-term nicotine treatment on locomotion, exploration and memory in young and old rats. Alessandri, B; Bätig, K; Oettinger, R; Welzl, H, 1988)	1.3
"Nicotine-treated HFF exhibited a haphazard arrangement with cell overlapping and vacuolization of the cytoplasm."	( The effect of nicotine on the attachment of human fibroblasts to glass and human root surfaces in vitro. Hanson, BS; McPherson, JC; McQuade, MJ; Raulin, LA, 1988)	1.36
"Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals."	( Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice. Collins, AC; de Fiebre, CM, )	1.16
"The nicotine treatment did not alter the ability of muscimol to inhibit the hyperactivity elicited by apomorphine."	( Effect of nicotine on central GABAergic system. Fung, YK; Reed, JA, 1988)	1.16
"The nicotine-treated group had greater myointimal thickening than did the hypertensive animals (p = 0.02)."	( Comparative effects of hypertension and nicotine on injury-induced myointimal thickening. Krupski, WC; Olive, GC; Rapp, JH; Weber, CA, 1987)	1.02
"Nicotine treatment also resulted in a significant increase in [3H]acetylcholine (3H-ACh) binding in the midbrain (48.3% increase in comparison with controls) and hippocampus (38.3% increase), whereas the binding of [3H]nicotine (3H-NIC) was unaffected in all brain areas investigated."	( Subchronic treatment of rats with nicotine: effects on tolerance and on [3H]acetylcholine and [3H]nicotine binding in the brain. Halén, A; Larsson, C; Nilsson, L; Nordberg, A, 1986)	1.27
"Nicotine-treated DBA mice developed a dose-related tolerance for most measures, whereas C3H mice did not appear to develop tolerance to any measure until the infusion dose reached 4 mg/kg/hr."	( Dose-response analysis of nicotine tolerance and receptor changes in two inbred mouse strains. Collins, AC; Marks, MJ; Stitzel, JA, 1986)	1.29
"The nicotine-treated group of rats was given water containing nicotine, which was estimated to be 10 mg/kg/day, for 40 days."	( [Influences of free intake of nicotine on several circadian rhythms in rats]. Kita, T; Kurogochi, Y; Nakanishi, Y; Nakashima, T, 1985)	1.04
"Treatment of nicotine dependence in the medical management of opioid dependence seems promising, but at what point in the course - simultaneously, shortly after, or far behind - has yet to be determined."	( [Nicotine, alcohol and opioids - three interacting substances]. Larsson, M, 2022)	1.98
"Pretreatment with nicotine (0.2 mg · kg"	( Nicotine pretreatment alleviates MK-801-induced behavioral and cognitive deficits in mice by regulating Pdlim5/CRTC1 in the PFC. Cheng, HQ; Geng, PP; Hu, XY; Jin, XC; Shu, H; Sun, YY; Wang, H; Wang, MW; Wang, Q; Wang, W; Wang, XN; Zhang, JF, 2023)	2.68
"Pretreatment with nicotine dose dependently inhibited acute pancreatitis caused by infusion of ERCP contrast solution into the main pancreatic duct in mice."	( Nicotinic stimulation of splenic T cells is protective in endoscopic retrograde cholangiopancreatography-induced acute pancreatitis in mice. Gunn, MD; Huang, MN; Liddle, RA; Shahid, RA; Vigna, SR, 2022)	1.04
"Treatment with nicotine or VEA alone or with PG/VG did not impact cell viability."	( An in vitro evaluation of e-vapor products: The contributions of chemical adulteration, concentration, and device power. Hoeng, J; Iskandar, AR; Johne, S; Majeed, S; Peitsch, MC; Torres, LO; van der Toorn, M, 2023)	1.25
"Treatment with nicotine for 14 days slightly polarized M0 microglia to M2b and d subtypes."	( Long-term Stimulation of α7 Nicotinic Acetylcholine Receptor Rescues Hemorrhagic Neuron Loss via Apoptosis of M1 Microglia. Deguchi, M; Inoue, A; Kurose, Y; Machida, A; Ohnishi, M; Takiyama, N, 2023)	1.25
"Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA)."	( GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity. Clemmensen, C; Dmytriyeva, O; Ejdrup, AL; Falk, S; Gether, U; Hecksher-Sørensen, J; Jørgensen, SH; Kohlmeier, KA; Krauth, N; Ludwig, MQ; Lundø, K; Nielsen, DAG; Pers, TH; Petersen, J; Romero-Leguizamón, CR; Roostalu, U; Skovbjerg, G; Svendsen, C, 2023)	1.64
"Treatment of nicotine toxicity is primarily supportive care directed at the presenting signs and symptoms."	( Acute Pediatric Liquid Nicotine Ingestions. Duong, M; Rosario, JM; Tweet, MS; Wilson, M, 2023)	1.57
"Treatment with nicotine replacement therapy (NRT) during an attempt to quit smoking increases the likelihood of success by about 55%. "	( Should Nicotine Replacement Therapy be Provided Free of Charge? A Cost-Utility Analysis in Sweden. Feldman, I; Galanti, MR; Gebreslassie, M; Lager, A, 2023)	1.72
"Treatment with nicotine caused a significant reduction in the levels of all reproductive hormones with significant diminution of some sperm parameters: motility, morphology and viability; and decrease in superoxide dismutase and increase in malondialdehyde concentration amongst Group B rats compared to Group A control rats (p<0.05)."	( Ameliorative Effects of Hydromethanolic Extract of Citrullus lanatus (Watermelon) Rind on Semen Parameters, Reproductive Hormones and Testicular Oxidative Status Following Nicotine Administration in Male Wistar Rats. Adienbo, O; Dapper, V; Kolawole, T, 2019)	1.05
"Treatment with nicotine decreased local levels of TNF-α and IL-1β, and increased the expression of GAP-43."	( Nicotine exerts neuroprotective effects by attenuating local inflammatory cytokine production following crush injury to rat sciatic nerves. Gao, T; Lan, Q; Mao, Y; Sheng, Z; Wang, D; Zhao, Y, 2019)	2.3
"Rats treated with nicotine for two months showed alterations in the oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG)), antioxidant enzymes (superoxide dismutase (SOD), catalase (Cat), glutathione enzymes (GPx and GST)) as well as several pro-inflammatory markers (Tumor Necrosis Factor-alpha (TNF-α), Interleukin-17 (IL-17), and Nuclear Factor-kappa B (NF-κB)), and induced apoptosis through Caspase-3 activity."	( Nicotine encourages oxidative stress and impairment of rats' brain mitigated by Spirulina platensis lipopolysaccharides and low-dose ionizing radiation. Elsonbaty, SM; Ismail, AFM, 2020)	2.32
"COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. "	( Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance are glucocorticoid-independent. Adeyanju, OA; Areola, ED; Michael, OS; Olatunji, LA; Soladoye, AO, 2017)	1.05
"Treatment with nicotine decreased AP and osteocalcin levels, increased TNF‑α and COX‑2 expression levels, and led to alveolar bone loss compared with the control group."	( Protective effect of catalpol on nicotine‑induced injury of alveolar bone and associated underlying mechanisms. Jin, X; Li, Y; Mao, L, 2017)	1.08
"Pre-treatment with nicotine significantly increased the levels of phosphorylated Akt, an effector of PI3K in astrocytes."	( Astrocytic α7 Nicotinic Receptor Activation Inhibits Amyloid-β Aggregation by Upregulating Endogenous αB-crystallin through the PI3K/Akt Signaling Pathway. Guan, Z; Ren, Z; Yang, M; Yu, W, 2019)	0.83
"Pretreatment with nicotine (1 μM) completely blocked the toxicities of Mn and Fe."	( Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: Implication for Parkinson's disease. Aschner, M; Csoka, AB; Getachew, B; Tizabi, Y, 2019)	2.28
"Pretreatment with nicotine reversed LPS-induced high levels of placental inflammatory cytokines, low levels of placental VEGF and placental pathological damage, then rescued the number and weights of live fetuses."	( Nicotine protects fetus against LPS-induced fetal growth restriction through ameliorating placental inflammation and vascular development in late pregnancy in rats. Bao, J; Garfield, RE; Liu, H; Liu, Y; Yuan, L; Zou, Y, 2019)	2.28
"Treatment with nicotine stimulated ERK1/2 and p38 MAPK phosphorylation in the PC12 cells expressing nNOS (NPC12 cells) as compared with that in control PC12 cells."	( Nitric oxide enhances increase in cytosolic Ca(2+) and promotes nicotine-triggered MAPK pathway in PC12 cells. Ihara, H; Kajiwara, A; Nozaki, N; Nyunoya, M; Takata, T; Tsuchiya, Y; Watanabe, Y, 2013)	0.97
"Treatment with nicotine plus LPS up-regulated the expression of resistin mRNA and the production of resistin protein in PDLCs in a time- and concentration-dependent manner. "	( Role of resistin in the inflammatory response induced by nicotine plus lipopolysaccharide in human periodontal ligament cells in vitro. Kang, KL; Kang, SI; Kang, SK; Kim, DK; Kim, EC; Lee, HJ; Lee, SY; Park, YD, 2015)	1.02
"The treatment with nicotine also significantly increased FGF-2 protein expression."	( Stimulation of α7 nicotinic acetylcholine receptor regulates glutamate transporter GLAST via basic fibroblast growth factor production in cultured cortical microglia. Harano, S; Hisaoka-Nakashima, K; Idenoshita, Y; Morioka, N; Nakata, Y; Tokuhara, M; Zhang, FF, 2015)	0.74
"Pretreatment with nicotine strongly alleviated severity of SAP-associated lung injury through attenuating serum amylase, lipase, and interleukin 6 levels; pancreas and lung pathological injury; lung myeloperoxidase activity; lung tumor necrosis factor-α; and high-mobility group box 1 expression. "	( Effects of Nicotine and Vagus Nerve in Severe Acute Pancreatitis-Associated Lung Injury in Rats. Chen, C; Chen, X; Ding, Y; He, X; Ma, P; Ren, J; Shi, Q; Wang, W; Yu, J; Yu, K; Zhao, K; Zuo, T, 2016)	1.16
"Mice treated with nicotine during early but not late adolescence showed an increase in CPP for cocaine, morphine and amphetamine later in adulthood."	( Early adolescent nicotine exposure affects later-life cocaine reward in mice. Alajaji, M; Carroll, FI; Damaj, MI; Kota, D; Lazenka, MF; Levine, A; Selley, DE; Sim-Selley, LJ; Wise, LE; Younis, RM, 2016)	1.1
"Treatment with nicotine (10 microM) or with the nicotinic receptor antagonists, mecamylamine (10 microM) or dihydro-beta-erythroidine (DHbetaE) (5 microM) efficiently prevented the diazoxon-induced reduction in alpha4 and beta2 nAChR mRNA and protein in PC12 cells, but carbamaylcholine, a weak nAChR agonist, was ineffective."	( Changes in mRNA and protein levels of nicotinic acetylcholine receptors in Diazoxon exposed pC12 cells. Golmanesh, L; Mehrani, H, 2008)	0.69
"men treated with nicotine patch suggests that increasing the quit rates of women smokers may require supplementing patch treatment or use of other medications."	( Sex differences in long-term smoking cessation rates due to nicotine patch. Perkins, KA; Scott, J, 2008)	0.92
"Treatment with nicotine polyestex gum resulted in significantly greater abstinence rate at 3 months compared with placebo (50% vs. "	( Effect of nicotine polyestex gum on smoking cessation and quality of life. Ekpanyaskul, C; Hattapornsawan, Y; Rungruanghiranya, S; Tundulawessa, Y, 2008)	1.1
"Pretreatment with nicotine during acquisition training significantly increased locomotor activity."	( Individual differences in response to novelty and the conditioned locomotor effects of nicotine. Cain, ME; Coolon, RA, 2009)	0.9
"Treatment with nicotine polyestex gum were reported 65.3% (130/199) at 4 weeks compared with failure 30.15% (60/199)[ 65.3% vs 30.15%; p = 0.005]."	( The bioequivalent and effect of nicotine formulation gum on smoking cessation. Chutrthong, W; Tundulawessa, K; Tundulawessa, Y; Yongchaiyud, P, 2010)	0.98
"Pretreatment with nicotine reduced the severity of intestinal lesions in a dose-dependent manner."	( Activation of α7 nicotinic acetylcholine receptors ameliorates indomethacin-induced small intestinal ulceration in mice. Amagase, K; Hashimura, H; Kato, S; Kawahara, R; Takeuchi, K; Yasuda, M, 2011)	0.69
"Treatment with nicotine increased the phosphorylation level of ERK1/2 in the NPC12 cells as compared with that in control PC12 cells."	( Nitric oxide promotes nicotine-triggered ERK signaling via redox reactions in PC12 cells. Ihara, H; Maeda, C; Miyamoto, Y; Sakai, R; Takata, T; Tsuchiya, Y; Watanabe, Y, 2011)	1.02
"Treatment with nicotine patches slowed recurrent lapse progression (HR = 0.58, CI = 0.48-0.70), but this effect dissipated over multiple lapses, and was moderated by elevated ratings of postlapse guilt (HR = 1.08, CI = 1.01-1.18), which predicted accelerated progression within the active patch group, while protecting against lapse in the placebo group."	( Relapse dynamics during smoking cessation: recurrent abstinence violation effects and lapse-relapse progression. Kirchner, TR; Shiffman, S; Wileyto, EP, 2012)	0.72
"Untreated and nicotine-treated neurons were compared from several regions of embryonic (E19) rat brain."	( Effects of chronic nicotine on heteromeric neuronal nicotinic receptors in rat primary cultured neurons. Hussmann, GP; Kellar, KJ; Lomazzo, E; Perry, DC; Wolfe, BB; Yasuda, RP, 2011)	1.04
"Pre-treatment with nicotine significantly restored Akt phosphorylation, an effector of PI3K, in Aβ(1-42) -treated neurons."	( α7 Nicotinic receptor activation reduces β-amyloid-induced apoptosis by inhibiting caspase-independent death through phosphatidylinositol 3-kinase signaling. Krantic, S; Mechawar, N; Quirion, R; Yu, W, 2011)	0.69
"Rats treated with nicotine alone showed robust locomotor sensitization, whereas rats pretreated with JMV 2959 showed significantly attenuated nicotine-induced hyperlocomotion."	( Pharmacologic antagonism of ghrelin receptors attenuates development of nicotine induced locomotor sensitization in rats. Brunel, L; Clifford, PS; Eitan, S; Fehrentz, JA; Hughes, S; Martinez, J; Rodriguez, J; Wellman, PJ, 2011)	0.94
"Pretreatment with nicotine caused a significant 2.5-fold inhibition of TNF-α-stimulated hBD-2 mRNA expression compared to TNF-α alone (p = 0.004). "	( HBD-1 and hBD-2 expression in HaCaT keratinocytes stimulated with nicotine. Kielbassa, AM; Liodakis, S; Pries, AR; Wolgin, M; Zakrzewicz, A, 2012)	0.95
"Oral treatment with nicotine dose dependently preserved renal function and halted proteinuria progression, which were independent of blood pressure reduction."	( Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria. Agarwal, PK; Bakker, SJ; Gans, RO; Navis, G; van den Born, J; van Goor, H, 2012)	0.96
"Treatment with nicotine significantly enhances CaMKП phosphorylation."	( Involvement of nicotinic acetylcholine receptor in the proliferation of mouse induced pluripotent stem cells. Goshima, H; Ishizuka, T; Ozawa, A; Watanabe, Y, 2012)	0.72
"Treatment with nicotine reduced cell viability and increased the proportion of annexin V-negative, propidium iodide-positive cells, an indication of cell death. "	( Endoplasmic reticulum stress modulates nicotine-induced extracellular matrix degradation in human periodontal ligament cells. Herr, Y; Kang, KL; Kim, EC; Lee, SI; Lee, YM; Shin, SI, 2012)	1
"Pretreatment with nicotine, dose-dependently blocked this toxicity."	( Protective effects of nicotine against aminochrome-induced toxicity in substantia nigra derived cells: implications for Parkinson's disease. Caviedes, P; Cuevas, C; Huenchuguala, S; Muñoz, P; Paris, I; Segura-Aguilar, J; Tizabi, Y; Villa, M, 2012)	1.02
"Pretreatment with nicotine and α₄β₂ ligands dose dependently reduced the binding of ZW-104 in the thalamus."	( Rat thalamic α₄β₂ neuronal nicotinic acetylcholine receptor occupancy assay using LC-MS/MS. Ajjala, DR; Bhyrapuneni, G; Kandikere, V; Muddana, N; Nirogi, R; Saralaya, R, )	0.45
"Treatment with nicotine prevented decreased expression and altered localization of occludin and ZO-1, as seen in animals undergoing burn alone."	( Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: a cholinergic agonist prevents gut barrier failure after severe burn injury. Bansal, V; Cheadle, GA; Coimbra, R; Costantini, TW; Eliceiri, BP; Hageny, AM; Krzyzaniak, M; Lopez, N; Putnam, JG, 2012)	0.72
"Treatment with nicotine significantly ameliorated the PPI deficits observed in DAT KO mice."	( Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine. Fukui, A; Hall, FS; Kasahara, Y; Sora, I; Uchiumi, O; Uhl, GR, 2013)	0.94
"Treatment with nicotine or NNK attenuated apoptosis caused by etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a transformed phenotype manifest as loss of contact inhibition and loss of dependence on exogenous growth factors or adherence to ECM."	( Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. Belinsky, S; Brognard, J; Clark, AS; Dennis, PA; Harris, C; Linnoila, IR; Swain, SM; West, KA; Yang, X, 2003)	0.97
"Rats treated with nicotine had lower IL-6 and IL-2 blood levels compared to control rats."	( Divergent effects of nicotine administration on cytokine levels in rat small bowel mucosa, colonic mucosa, and blood. Eliakim, R; Karmeli, F, 2003)	0.96
"Treatment with nicotine markedly upregulated NGF mRNA and protein expression in spinal cord neurons."	( Nicotine upregulates nerve growth factor expression and prevents apoptosis of cultured spinal cord neurons. Garrido, R; Hennig, B; King-Pospisil, K; Son, KW; Toborek, M, 2003)	2.1
"Pretreatment with nicotine decreased glutamate-mediated calcium influx in primary cortical cultures by 41%, an effect that was absent in cultures from knock-out mice lacking the beta2 subunit of the nAChR."	( Neuroprotection by nicotine in mouse primary cortical cultures involves activation of calcineurin and L-type calcium channel inactivation. Fitzsimonds, RM; Krueger, SR; Picciotto, MR; Stevens, TR, 2003)	0.97
"Pretreatment with nicotine 1-20 micro M resulted in a dose-dependent protection against ethanol-induced toxicity."	( Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells. Al-Namaeh, M; Manaye, KF; Taylor, RE; Tizabi, Y, 2003)	0.96
"Treatment with nicotine before training session prolonged the latencies significantly (p < .01)."	( Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement. Bahçekapili, N; Díler, AS; Tasyüreklí, M; Uzüm, G; Zíylan, YZ, 2004)	2.11
"The treatment of nicotine dependent smokers bases on nicotine replacement therapy and on use of bupropion."	( [Methods and cost effectiveness of nicotine abstinence]. Górecka, D, 2004)	0.93
"Pretreatment with nicotine 5-20 microM resulted in a dose-dependent protection against ethanol-induced toxicity."	( Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Manaye, KF; Smoot, DT; Taylor, RE; Tizabi, Y, 2004)	2.09
"Pretreatment with nicotine abolished corticosterone-activating effect of this drug only in adult animals, indicating the development of tolerance at this age."	( Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats. Cruz, FC; Delucia, R; Planeta, CS, 2005)	0.89
"treatment with nicotine (from 5 to 20 g) dose-dependently blocked pain behavior revealed during the second phase, but not during the first phase in the formalin test."	( Antinociceptive effect of nicotine in various pain models in the mouse. Choi, SS; Han, KJ; Kwon, MS; Lee, HK; Lee, JY; Seo, YJ; Shim, EJ; Suh, HW, 2005)	0.97
"Treatment with nicotine patch or lozenge is effective for women, and the analysis did not reveal significant gender differences in efficacy."	( Nicotine patch and lozenge are effective for women. Dresler, CM; Shiffman, S; Sweeney, CT, 2005)	2.11
"Posttreatment of nicotine-damaged DNA by endonuclease III and formamidopyrimidine-DNA glycosylase, recognizing oxidized DNA bases, increased the extent of DNA damage."	( Effects of pH on nicotine-induced DNA damage and oxidative stress. Chi, CW; Liu, TY; Wu, HJ, 2005)	1
"Pretreatment with nicotine (5-20 microM) dose dependently attenuated these effects of ethanol."	( Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells. Manaye, KF; Taylor, RE; Tizabi, Y, 2005)	2.09
"Treatment with nicotine also resulted in less glial fibrillary acidic protein immunoreactive astrocytes around the plaques, increased levels of synaptophysin, and increased number of alpha7 nicotinic acetylcholine receptors (nAChRs) in the cortex of APPswe transgenic mice."	( Effect of subchronic treatment of memantine, galantamine, and nicotine in the brain of Tg2576 (APPswe) transgenic mice. Hedberg, MM; Nordberg, A; Svedberg, MM; Unger, C; Yu, WF, 2006)	0.91
"Treatment of nicotine with lithium powder and chlorotrimethylsilane afforded 1,4-bis(trimethylsilyl)-1,4-dihydronicotine in high yield."	( Synthesis of nicotine derivatives via reductive disilylation of (S)-nicotine. Comins, DL; Février, FC; Smith, ED, 2006)	1.06
"Treatment with nicotine (0.6 and 0.8 mg kg(-1)) also significantly reduced the number of amphetamine-induced rotations compared to vehicle treatment."	( Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle. Duty, S; O'Neill, MJ; Visanji, NP, 2006)	2.12
"Mice treated with nicotine (0.16 mg/kg) attained significantly higher response accuracy and had a lower percentage of incorrect responses in comparison with the solvent-treated animals."	( Attentional performance of (C57BL/6Jx129Sv)F2 mice in the five-choice serial reaction time task. de Bruin, NM; Duytschaever, H; Fransen, F; Grantham, C; Megens, AA, 2006)	0.66
"Pretreatment with nicotine significantly decreased each of these markers in vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham-operated DSS-treated mice."	( The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Blennerhassett, P; Collins, SM; Ghia, JE; Kumar-Ondiveeran, H; Verdu, EF, 2006)	0.66
"Treatment with nicotine also resulted in regulation of a number of genes that were not regulated by PNU-282987, consistent with the interaction of nicotine with other nAChRs beyond the alpha7 subtype."	( Analysis of gene expression profiles in rat hippocampus following treatment with nicotine and an alpha7 nAChR selective agonist. Abel, S; Anderson, DJ; Bitner, RS; Blomme, EA; Gopalakrishnan, M; Li, J; Nikkel, AL; Waring, JF, 2008)	0.91
"Mice treated with nicotine, mecamylamine or both drugs tested 5 hr after withdrawal were less sensitive to acute injection with nicotine than were saline-infused mice."	( Sensitivity to nicotine and brain nicotinic receptors are altered by chronic nicotine and mecamylamine infusion. Collins, AC; Luo, Y; Marks, MJ; Selvaag, S, 1994)	0.97
"Pretreatment with nicotine suppressed the sympathetic activity induced by immobilization stress to the same extent as that observed after administering nicotine alone."	( Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress. Kondo, M; Sakane, N; Umekawa, T; Yoshida, T, 1994)	1.01
"Treatment with nicotine caused a significant inhibition of IL-10 production by NAC. "	( In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Feyerabend, C; Madretsma, S; Tak, CJ; van Dijk, JP; Wilson, JH; Wolters, LM; Zijlstra, FJ, 1996)	0.98
"Treatment with nicotine has been shown to influence all aspects of the immune system, including alterations in humoral and cellular immunity."	( The effects of nicotine on the immune system. Caggiula, AR; Donny, EC; Knopf, S; McAllister-Sistilli, CG; Miller, AL; Rose, CA, 1998)	0.99
"Pretreatment with nicotine caused a significant inhibition of LPS-induced IL-1, IL-8, and PGE2 expression at the transcriptional level in U937 cells."	( Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation. Ito, K; Murai, S; Shimada, K; Sugano, N, 1998)	2.07
"Pretreatment with nicotine (0.4 mg/kg s.c."	( The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to D-amphetamine. Balfour, DJ; Birrell, CE, 1998)	0.96
"Treatment with nicotine reduced the binding of both radiotracers."	( Comparative studies of epibatidine derivatives [18F]NFEP and [18F]N-methyl-NFEP: kinetics, nicotine effect, and toxicity. Carroll, FI; Ding, YS; Fowler, JS; Kuhar, MJ; Logan, J; Molina, PE; Volkow, ND, 1999)	0.86
"Pretreatment with nicotine decreased AA-induced overexpression of nNOS and elevation of nitrite levels."	( Nicotine attenuates arachidonic acid-induced overexpression of nitric oxide synthase in cultured spinal cord neurons. Garrido, R; Hennig, B; Kaiser, S; Malecki, A; Mattson, MP; Toborek, M; Young, B, 2000)	2.07
"Mice treated with nicotine (0.5 mg/kg) or saline every other day for 8 days (four drug and four saline sessions) developed CPP that was completely blocked by pretreatment with 7-NI (25 mg/kg)."	( 7-Nitroindazole blocks nicotine-induced conditioned place preference but not LiCl-induced conditioned place aversion. Itzhak, Y; Martin, JL, 2000)	0.94
"Treatment with nicotine-di-D tartrate (1 mg/kg, sc) disrupted this effect."	( Individual differences in rat locomotor activity are diminished by nicotine through stimulation of central nicotinic acetylcholine receptors. Besheer, J; Bevins, RA, 2001)	0.89
"Treatment with nicotine, but not placebo, briefly reversed the inhibitory abnormality on both test days."	( Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism. Adler, LE; Amass, L; Cawthra, E; Freedman, R; Hoffer, M; Nagamoto, HT; Olincy, A, 2001)	0.65
"Treatment with nicotine (1-100 microM) for 3 days significantly increased the specific binding of [(3)H]epibatidine and [(3)H]cytisine in cortical cells but not in cells from subcortical forebrain and mesencephalon brain regions, indicating region-specific differences in the sensitivity to nicotine exposure."	( Nicotine-induced alterations in the expression of nicotinic receptors in primary cultures from human prenatal brain. Hellström-Lindahl, E; Kjaeldgaard, A; Nordberg, A, 2001)	2.09
"Pre-treatment with nicotine, at 10(-7)-10(-4) M, partially prevented the toxin-induced decline in dopaminergic cells."	( Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture. Jeyarasasingam, G; Quik, M; Tompkins, L, 2002)	0.63
"In untreated cells, nicotine increased [Ca(2+)](i) (EC(50) 7.5 microM)."	( Effects of chronic drug treatments on increases in intracellular calcium mediated by nicotinic acetylcholine receptors in SH-SY5Y cells. Pakkanen, J; Ridley, DL; Wonnacott, S, 2002)	0.63
"Treatment with nicotine replacement therapy or bupropion doubles the one-year success rate after cessation of smoking."	( [Treatment of nicotine addiction. Drug therapy for smoking cessation]. Christensen, HR; Døssing, M; Pedersen, ST, 2002)	1.01
"Treatment with nicotine or the cotransfection of TR3 expression vector inhibited the induction of RAR beta promoter activity by trans-RA in transient transfection assays."	( Nicotine modulates the effects of retinoids on growth inhibition and RAR beta expression in lung cancer cells. Chen, GQ; Dawson, MI; Lin, B; Zhang, XK, 2002)	2.1
"Pretreatment with nicotine (0.1 or 0.4 mg kg-1 daily for 5 days) enhanced the effects of the drug on spontaneous locomotor activity and enhanced the effects of the drug on extracellular levels of dopamine to the extent that the response became significant (P less than 0.05)."	( The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Balfour, DJ; Benwell, ME, 1992)	0.89
"Treatment with nicotine suppressed, in a dose dependent fashion, the ability of splenic T lymphocytes to respond to mitogen, but dramatically enhanced the ability of mitogen stimulated lymphocytes to generate IL2."	( Nicotine enhances interleukin production of rat splenic T lymphocytes. Fung, YK; Peterson, DS; Petro, TM, 1992)	2.07
"Treatment with nicotine chewing-gum and group or individual support."	( [Intervention against tobacco dependence in primary care. A study of 4 modalities of action]. Corral, C; Pascual, M, 1992)	0.62
"Treatment with nicotine 5 or 25 micrograms/ml did not influence the number of gastric mucosal mast cells degranulated by cold and restraint; however, drinking 50 micrograms/ml for 10 days lowered further the mast cell count in stressed animals."	( Chronic nicotine treatment intensifies gastric ulceration by cold-restraint stress in rats. Cho, CH; Ogle, CW; Qiu, BS, 1991)	1.06
"The treatments, nicotine chewing gum and acupuncture, were randomly allocated."	( [A study of various smoking cessation programs based on close to 1000 volunteers recruited from the general population: 1-month results]. Clavel, F; Paoletti, C, 1990)	0.61
"Treatment with nicotine for 10 days (s.c."	( Effects of chronic administration of nicotine on prolactin release in the rat: inactivation of prolactin response by repeated injections of nicotine. Hulihan-Giblin, BA; Kellar, KJ; Lumpkin, MD, 1990)	0.89
"Pre-treatment with nicotine, which temporarily inactivates cholinergic receptor-activated calcium channels, did not affect [Ca++]i responses to AII."	( Angiotensin II increases cytosolic calcium and stimulates catecholamine release in cultured bovine adrenomedullary cells. Goldstein, DS; Keiser, HR; Stull, R; Zimlichman, R; Zimlichman, S, 1987)	0.59
"Treatment with nicotine (0.001-2.0 mg/kg tended to improve performance but this did not reach statistical significance."	( Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects. Field, MJ; Iversen, SD; Jennings, CA; Rupniak, NM; Steventon, MJ, 1989)	0.62
"Pretreatment of nicotine did not alter the characteristics of [3H]spiperone binding to striatal dopamine receptors."	( Acute effect of nicotine on the striatal dopaminergic system in the rat. Fung, YK; Lau, YS, 1986)	0.95
"Treatment with nicotine mimicked the effects of tobacco smoke exposure."	( Enhanced chemotaxis and superoxide anion production by polymorphonuclear leukocytes from nicotine-treated and smoke-exposed rats. Gillespie, MN; Jay, M; Kojima, S; Owasoyo, JO, 1987)	0.83
"Pretreatment with nicotine, alcohol, and their combination resulted in the significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine."	( Effect of nicotine and alcohol pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. Ageel, AM; Parmar, NS; Tariq, M, )	0.86
"Pretreatment with nicotine, caffeine, and their combination resulted in significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine."	( Effect of nicotine and caffeine pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. Ageel, AM; Parmar, NS; Tariq, M, 1985)	1
"Pretreatment with nicotine, alcohol and caffeine and their combination resulted in a significant augmentation of gastric lesions produced by aspirin, phenylbutazone and reserpine."	( Effect of nicotine, alcohol and caffeine pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats. Ageel, AM; Parmar, NS; Tariq, M, 1985)	1
"The treatment of nicotine induced a dose-dependent increase in ambulatory activity."	( Effects of oral administration of nicotine on circadian rhythms of ambulatory activity and drinking in rats. Kita, T; Kurogochi, Y; Nakashima, T, 1985)	0.88

Toxicity

Nicotine replacement therapy (NRT) increases quit rates. Vitamin C supplementation mitigated the harmful effects of prenatal nicotine exposure on placental hemodynamics and development.

Excerpt	Reference	Relevance
" As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP+ in the storage vesicle."	( Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells. Daniels, AJ; Diliberto, EJ; Reinhard, JF; Viveros, OH, 1987)	0.27
"Nicotine is a toxic substance which is readily available from a wide variety of sources."	( Suicide plan by nicotine poisoning: a review of nicotine toxicity. Saxena, K; Scheman, A, 1985)	2.06
"To evaluate potential adverse effects from inadvertent exposure to a nicotine transdermal system or "patch", three marketed products were administered topically and orally to dogs: Nicoderm (nicotine transdermal system), with a drug reservoir and a rate-controlling membrane; Nicotinell, with a nicotine solution dispersed in a cotton gauze pad between layers of adhesive; and Niconil, with a nicotine gel matrix."	( Absorption and adverse effects following topical and oral administration of three transdermal nicotine products to dogs. Gorsline, J; Matsushima, D; Prevo, ME, 1995)	0.74
"The nicotine skin patch proved to be safe and well tolerated."	( The safety, tolerability and efficacy of transdermal nicotine (Nicotinell TTS) in initially hospitalised patients. Martin, PD; Robinson, GM, 1995)	1.1
"NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serous side effects."	( Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group. Bailey, WC; Bjornson, WM; Connett, JE; Daniels, K; Kiley, JP; Kurnow, K; Murray, RP; Nides, MA, 1996)	0.7
" The subject was not smoking and the adverse event was deemed to be not related to the patch therapy."	( High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Croghan, IT; Fredrickson, PA; Gomez-Dahl, L; Hurt, RD; Lauger, G; Lee, GM; Offord, KP; Wingender, L, 1995)	0.61
" Since nicotine is believed to be the primary constituent of cigarette smoke responsible for its acute adverse effects on myocardial oxygen supply and demand, concomitant nicotine replacement therapy and smoking theoretically could provoke a marked decrease in myocardial oxygen supply and increase in demand."	( Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions. Conrad, K; Foerster, EH; Hillis, LD; Keeley, EC; Landau, C; Lange, RA; Pirwitz, MJ; Willard, JE, 1996)	1.14
" These data suggest that humans acutely develop tolerance to an increasing nicotine concentration, thereby helping to explain the apparent lack of a potential synergistic adverse effect associated with continued smoking during nicotine replacement therapy."	( Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions. Conrad, K; Foerster, EH; Hillis, LD; Keeley, EC; Landau, C; Lange, RA; Pirwitz, MJ; Willard, JE, 1996)	0.91
" Clinical considerations regarding the problems of toxic effects of nicotine in human and molecular basis of carcinogen mechanism of nicotine derivatives are discussed."	( [Metabolism of nicotine--mechanism and clinical effects of toxicity]. Kwiatkowska, D; Szajerka, G, 1997)	0.89
" After exercise, subjects taking Habitrol tended to have a higher incidence of adverse events compared with baseline values."	( Plasma levels of nicotine and safety of smokers wearing transdermal delivery systems during multiple simultaneous intake of nicotine and during exercise. Besner, JG; Caillé, G; Gossard, D; Homsy, W; Houle, JM; Pierce, CH; Yan, K, 1997)	0.64
"Although nicotine nasal spray causes substantial irritant side effects during the first few days of use, these adverse effects decrease significantly within the first week."	( Nicotine nasal spray for smoking cessation: pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels. Croghan, GA; Croghan, IT; Dale, LC; Gomez-Dahl, LC; Hurt, RD; Offord, KP, 1998)	2.16
"To estimate the frequency of adverse effects associated with the use of the transdermal nicotine patch, we abstracted and analysed data from 47 reports of 35 clinical trials."	( A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Greenland, S; Lanes, SF; Satterfield, MH, 1998)	0.74
" The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking."	( Increase of formation of methylamine and formaldehyde in vivo after administration of nicotine and the potential cytotoxicity. Yu, PH, 1998)	0.8
" Safety was evaluated by self-reported adverse events."	( Efficacy and safety of an over-the-counter transdermal nicotine patch as an aid for smoking cessation. Burt, R; Davidson, M; Epstein, M; McDonald, A; Schaefer, C; Whitworth, G, )	0.38
" At least 1 adverse event was reported by 57% receiving the nicotine patch and 39% receiving placebo (P<."	( Efficacy and safety of an over-the-counter transdermal nicotine patch as an aid for smoking cessation. Burt, R; Davidson, M; Epstein, M; McDonald, A; Schaefer, C; Whitworth, G, )	0.62
" Nicotine was 100-fold more toxic than cotinine and 10-fold more rapid than cotinine at producing respiratory arrest."	( Evidence that nicotine acetylcholine receptors are not the main targets of cotinine toxicity. Baziard-Mouysset, G; Belahsen, Y; Courriere, P; Dousset, JC; Riah, O; Stigliani, JL, 1999)	1.57
" The presence of neuronal nicotinic receptors sensitive to nicotine in tissues known to be involved in tobacco toxicity, like bronchi and blood vessels, raises the possibility that they mediate some of the toxic effects of smoking."	( Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity? Conti-Fine, BM; Lei, S; Maus, AD; Navaneetham, D, 2000)	0.55
"The present study directly compared the antinociceptive and toxic effects of the neuronal nicotinic receptor agonist ABT-594 ((R)-5-(2-azetidinylmethoxy)-2-chloropyridine) with (-)-nicotine and (+)-epibatidine."	( Analgesic and toxic effects of ABT-594 resemble epibatidine and nicotine in rats. Boyce, S; Hill, RG; Rupniak, NMJ; Russell, MGN; Shepheard, SL; Webb, JK, 2000)	0.74
" Copper supplementation during gestation and lactation prevented the adverse effects of maternal nicotine exposure during gestation and lactation on the development of the alveolar region of the rat lung."	( Maternal copper supplementation protects the neonatal rat lung against the adverse effects of maternal nicotine exposure. Aalbers, J; Maritz, GS; Matthews, HL, 2000)	0.74
" Because nicotine has adverse effects, it is important to conduct a systematic review to assess the clinical efficacy and safety of nicotine for patients with AD OBJECTIVES: To evaluate the efficacy and safety of nicotine, administered in any way or form, for people with Alzheimer's disease."	( Efficacy and safety of nicotine on Alzheimer's disease patients. López-Arrieta, JM; Rodríguez, JL; Sanz, F, 2001)	1.04
" This study examines the hypothesis for the first time that the neonicotinoid insecticides and their imine metabolites and analogs display analgesic (antinociceptive) activity or adverse toxic effects associated with their action on binding to the alpha 4 beta 2 nicotinic acetylcholine receptor (AChR) subtype."	( Analgesic and toxic effects of neonicotinoid insecticides in mice. Casida, JE; Cowan, A; Tomizawa, M, 2001)	0.31
" Adverse events associated with the use of bupropion SR at the recommended dosage of 150mg twice daily in clinical trials most commonly included insomnia, headache, dry mouth, nausea and anxiety; insomnia and anxiety are also recognised as symptoms of nicotine withdrawal."	( Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Aubin, HJ, 2002)	0.5
" Knowledge reviewed here of the functional architecture and molecular aspects of the insect and mammalian nAChRs and their neonicotinoid-binding site lays the foundation for continued development and use of this new class of safe and effective insecticides."	( Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors. Casida, JE; Tomizawa, M, 2003)	0.32
" Copper supplementation during this period of lung development reduced the adverse effect of maternal nicotine exposure on neonatal lung development."	( Is maternal copper supplementation during alveolarization protecting the developing rat lung against the adverse effects of maternal nicotine exposure? A morphometric study. Maritz, GS; Windvogel, S, 2003)	0.74
" Studies to test the efficacy of bupropion for smoking cessation and depression suggest it is safe to use in cardiac disease patients despite recent case reports of adverse events associated with bupropion use."	( Safety issues in pharmacotherapy for smoking in patients with cardiovascular disease. Fu, SS; Joseph, AM, )	0.13
" After having received over-the-counter (OTC) status in Germany, concerns grew about effectiveness, increased risks, especially of adverse cardiovascular reactions, and inappropriate use of NRT."	( A naturalistic cohort study on effectiveness, safety and usage pattern of an over-the-counter nicotine patch. Cohort study on smoking cessation. Fagerstrom, KO; Hasford, J; Haustein, KO, 2003)	0.54
" Therefore, nicotine replacement is recognized as a relatively safe and effective aid to smoking cessation."	( Are nicotine replacement strategies to facilitate smoking cessation safe? Birek, C; Lavelle, C; Scott, DA, 2003)	1.26
" In addition to the stimulatory effects of both ethanol and nicotine on the mesolimbic reward pathway, nicotine's ability to counteract some of the adverse effects of ethanol (e."	( Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells. Al-Namaeh, M; Manaye, KF; Taylor, RE; Tizabi, Y, 2003)	0.88
"The underlying cause of Alzheimer's disease is thought to be the aggregation of monomeric beta-amyloid (Abeta), through a series of toxic oligomers, which forms the mature amyloid fibrils that accumulate at the center of senile plaques."	( Both the D-(+) and L-(-) enantiomers of nicotine inhibit Abeta aggregation and cytotoxicity. Allsop, D; El-Agnaf, OM; Fullwood, NJ; Gibson, GL; Huckerby, TN; Moore, SA; Tabner, BJ; Turnbull, S, 2004)	0.59
" Given that cigarette smoking is highly prevalent in some of these patient groups and nicotine has been shown to reduce toxic consequences of NMDA receptor function, it may be suggested that nicotine intake may attenuate the neurotoxic effects of hypercortisolemia."	( (-)-nicotine ameliorates corticosterone's potentiation of N-methyl-d-aspartate receptor-mediated cornu ammonis 1 toxicity. Harris, BR; Littleton, JM; Mulholland, PJ; Prendergast, MA; Self, RL, 2004)	1.1
"Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption."	( Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Buss, DC; Evans, BK; Feyerabend, C; Ingram, JR; Marshall, RW; Rhodes, J; Routledge, P; Thomas, GA, 2004)	2.15
" Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine."	( Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Buss, DC; Evans, BK; Feyerabend, C; Ingram, JR; Marshall, RW; Rhodes, J; Routledge, P; Thomas, GA, 2004)	1.99
" Eleven of 14 adverse events were 'early'--30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the tmax."	( Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Buss, DC; Evans, BK; Feyerabend, C; Ingram, JR; Marshall, RW; Rhodes, J; Routledge, P; Thomas, GA, 2004)	1.98
"The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events."	( Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Buss, DC; Evans, BK; Feyerabend, C; Ingram, JR; Marshall, RW; Rhodes, J; Routledge, P; Thomas, GA, 2004)	2.11
" An alternate metabolic route entails hydrolysis of nicotine iminium to an open-chain ketoamine that, in turn, undergoes nitrosation to form a toxic nitrosamine."	( Iminium metabolite mechanism for nicotine toxicity and addiction: Oxidative stress and electron transfer. Cooksy, A; Kovacic, P, 2005)	0.86
"The high incidence of smoking among alcoholics may be partially due to nicotine's ability to counteract some of the adverse effects of ethanol on motor coordination and/or cognitive functions."	( Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Manaye, KF; Smoot, DT; Taylor, RE; Tizabi, Y, 2004)	2
"Nicotine, a major toxic component of cigarette smoke has been identified as a major risk factor for lung related diseases."	( Curcumin ameliorates oxidative stress during nicotine-induced lung toxicity in Wistar rats. Kalpana, C; Menon, VP, 2004)	2.03
"Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of < or =6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers."	( Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Cadet, JL; Ernst, M; Heishman, SJ; Moolchan, ET; Pickworth, WB; Robinson, ML; Schroeder, JR, 2005)	0.63
" Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials."	( Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Cadet, JL; Ernst, M; Heishman, SJ; Moolchan, ET; Pickworth, WB; Robinson, ML; Schroeder, JR, 2005)	0.63
" Transdermal nicotine therapy appears safe and does not have an effect on the mortality of patients with acute coronary syndromes."	( Safety and effectiveness of transdermal nicotine patch in smokers admitted with acute coronary syndromes. Jollis, JG; Meine, TJ; Pappas, PA; Patel, MR; Washam, JB, 2005)	0.97
" The vaccine was safe and well-tolerated."	( A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. Bachmann, MF; Jennings, GT; Lindman, Y; Maurer, P; Müller, P; Renner, WA; Rohner, F; Roubicek, K; Willers, J, 2005)	0.63
" We investigated the possible existence of adverse effects as well as the severity of each adverse effect and its influence on the treatment course."	( Adverse effects of pharmacological therapy for nicotine addiction in smokers following a smoking cessation program. Barrueco, M; Jiménez-Ruiz, C; Otero, MJ; Palomo, L; Riesco, JA; Romero, P; Torrecilla, M, 2005)	0.59
"Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer."	( Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats. Kalpana, C; Menon, VP; Rajasekharan, KN, 2005)	1.99
" Results showed that the nicotine vaccine was safe and well tolerated."	( Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. de Vos, A; Fiore, M; Hatsukami, DK; Horwith, G; Jorenby, D; Koopmeiners, J; Pentel, PR; Rennard, S, 2005)	0.92
" The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55."	( Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week, randomized, open-label study. Choi, JH; Dresler, CM; Gamble, ML; Marsh, HS; Strahs, KR; Targett, DA, 2005)	0.65
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."	( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004)	0.32
" Adverse effects (AEs) were mostly drug-related local symptoms, most frequently reported at the end of the tryout period: out of 106 drug-related AEs, 90 were due to the spray, 11 and 5 to the inhaler and gum, respectively."	( A nicotine mouth spray for smoking cessation: a pilot study of preference, safety and efficacy. Axelsson, A; Bolliger, CT; van Biljon, X, 2007)	1.06
" Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for lung-related diseases."	( Comparative effects of curcumin and its synthetic analogue on tissue lipid peroxidation and antioxidant status during nicotine-induced toxicity. Kalpana, C; Menon, VP; Rajasekharan, KN; Sudheer, AR, 2007)	1.46
"We evaluated mechanisms contributing to the adverse effects of chlorpyrifos (CPF) on DNA synthesis, cell number and size, and cell signaling mediated by adenylyl cyclase (AC) in PC12 cells, a neuronotypic cell line that recapitulates the essential features of developing mammalian neurons."	( Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells. MacKillop, EA; Ryde, IT; Seidler, FJ; Slotkin, TA, 2007)	0.34
" Nicotine, which stimulates nicotinic acetylcholine receptors but also possesses a mixture of prooxidant/antioxidant activity, had adverse effects by itself but also protected undifferentiated cells from the actions of CPF and had mixed additive/protective effects on cell number in differentiating cells."	( Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells. MacKillop, EA; Ryde, IT; Seidler, FJ; Slotkin, TA, 2007)	1.25
"Our results show definitive contributions of cholinergic hyperstimulation, oxidative stress, and interference with AC signaling in the developmental neurotoxicity of CPF and point to the potential use of this information to design treatments to ameliorate these adverse effects."	( Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells. MacKillop, EA; Ryde, IT; Seidler, FJ; Slotkin, TA, 2007)	0.34
" Nicotinell lozenges were found to be safe with mainly mild and reversible adverse events."	( Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell). Callens, A; Dautzenberg, B; Kienzler, JL; Nides, M, 2007)	1.47
" To determine the suitability of this model for screening inhaled toxicants, the EpiAirway tissue model (ETM) was treated apically with tobacco smoke components (nicotine, formaldehyde, cadmium, urethane) which are known to induce a variety of toxic effects (e."	( An in vitro approach to assess the toxicity of inhaled tobacco smoke components: nicotine, cadmium, formaldehyde and urethane. Balharry, D; BéruBé, KA; Sexton, K, 2008)	0.77
" Clinical safety was determined by vital signs, reactogenicity, and adverse events, and immunogenicity was measured by enzyme-linked immunosorbent assay."	( The immunogenicity and safety of a nicotine vaccine in smokers and nonsmokers: results of a randomized, placebo-controlled phase 1/2 trial. de Vos, A; Horwith, G; van Schayck, CP; Wagena, EJ, 2008)	0.62
"Biochemically validated 4-week continuous abstinence at end-of-treatment (weeks 6-9; primary end-point); 7-day point prevalence abstinence at weeks 9 and 24; sustained abstinence (weeks 6-24); change in body weight; and adverse events."	( A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain. Chang, Y; Dale, LC; Gonzales, D; Lawrence, D; Rigotti, NA, 2009)	0.61
" Serious adverse event rates did not differ between groups."	( A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain. Chang, Y; Dale, LC; Gonzales, D; Lawrence, D; Rigotti, NA, 2009)	0.61
"Nicotine replacement therapy (NRT) increases quit rates and is increasingly distributed through quitlines, but no systematic data are available on adverse effects and safety among quitline NRT users."	( Adverse effects with use of nicotine replacement therapy among quitline clients. Abrams, SM; Cummings, KM; Mahoney, MC; Ossip, DJ; Sall, D, 2009)	2.09
" All were asked about their use of NRT and adverse effects."	( Adverse effects with use of nicotine replacement therapy among quitline clients. Abrams, SM; Cummings, KM; Mahoney, MC; Ossip, DJ; Sall, D, 2009)	0.65
"Among those who reported having used NRT at the 2-week contact, about one in four reported an adverse effect."	( Adverse effects with use of nicotine replacement therapy among quitline clients. Abrams, SM; Cummings, KM; Mahoney, MC; Ossip, DJ; Sall, D, 2009)	0.65
"The prevalence and types of adverse effects observed among smokers receiving NRT were as expected with product labeling and support the conclusion that the distribution of over-the-counter NRT through quitlines is safe as long as clients are screened adequately per the labeling instructions."	( Adverse effects with use of nicotine replacement therapy among quitline clients. Abrams, SM; Cummings, KM; Mahoney, MC; Ossip, DJ; Sall, D, 2009)	0.65
" Other outcomes were cessation and reduction at end of follow-up, and adverse events."	( Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. Aveyard, P; Barton, P; Connock, M; Fry-Smith, A; Moore, D; Wang, D, 2009)	0.65
" Adverse side-effects associated with a gastrointestinal disorder occurred in 14 cases and 1 case in the VG and NG, respectively, and skin allergy was seen in 0 and 9 cases, respectively."	( A randomized controlled open comparative trial of varenicline vs nicotine patch in adult smokers: efficacy, safety and withdrawal symptoms (the VN-SEESAW study). Noda, K; Saku, K; Tsukahara, H, 2010)	0.6
"There is currently insufficient evidence to determine whether or not nicotine replacement therapy is effective or safe when used in pregnancy for smoking cessation; further research and, in particular, placebo-randomized controlled trials are required."	( Efficacy and safety of nicotine replacement therapy for smoking cessation in pregnancy: systematic review and meta-analysis. Chamberlain, C; Coleman, T; Cooper, S; Leonardi-Bee, J, 2011)	0.91
" Although each of the medications used for tobacco dependence treatment has been rigorously tested for efficacy and safety, broader experience in clinical trials and in observational population-based studies suggests that adverse events associated with these medications are relatively common."	( Adverse effects and tolerability of medications for the treatment of tobacco use and dependence. Ebbert, JO; Hays, JT, 2010)	0.36
" The toxic effects associated with STPs have been associated with trace level contaminants present in these products."	( Assessment of potential toxicity of a smokeless tobacco product (naswar) available on the Pakistani market. Gul, F; Humayun, M; Khan, H; Khan, SA; Khuda, F; Muhammad, N; Saeed, M, 2012)	0.38
"A total of 30 Pakistani brands of naswar were tested for a variety of toxic constituents and carcinogens such as cadmium, arsenic, lead and other carcinogenic metals, nitrite and nitrate, and nicotine and pH."	( Assessment of potential toxicity of a smokeless tobacco product (naswar) available on the Pakistani market. Gul, F; Humayun, M; Khan, H; Khan, SA; Khuda, F; Muhammad, N; Saeed, M, 2012)	0.57
" However, other known toxic agents, including chlorhexidine, ethanol, bacterial LPS and nicotine, do not appear to function synergistically to increase the deleterious cellular effects of the calcium hydroxide in an in vitro model of cytotoxicity."	( Chlorhexidine, ethanol, lipopolysaccharide and nicotine do not enhance the cytotoxicity of a calcium hydroxide pulp capping material. Byars, M; Falvo, J; Ruiz, F; Wheater, MA, 2012)	0.86
" Adverse events (AEs), related to pharmacotherapy, were monitored."	( Safety of varenicline among smokers enrolled in the lung HIV study. Browning, KK; Diaz, P; Ferketich, AK; Koletar, SL; Lu, B; Reynolds, NR; Wewers, ME, 2013)	0.39
" The aim of this study was to investigate the effect of green tea epigallocatechin-3-gallate on the nicotine-induced toxic and inflammatory responses in oral epithelial cells and gingival fibroblasts."	( Neutralizing effect of green tea epigallocatechin-3-gallate on nicotine-induced toxicity and chemokine (C-C motif) ligand 5 secretion in human oral epithelial cells and fibroblasts. Desjardins, J; Grenier, D, 2012)	0.83
" Pretreatment of cells with epigallocatechin-3-gallate efficiently neutralized the nicotine-induced toxic effects in epithelial cells and fibroblasts."	( Neutralizing effect of green tea epigallocatechin-3-gallate on nicotine-induced toxicity and chemokine (C-C motif) ligand 5 secretion in human oral epithelial cells and fibroblasts. Desjardins, J; Grenier, D, 2012)	0.84
" In summary, our study presents a novel approach to significantly improve nicotine vaccine immunogenicity by a combination of safe cutaneous vaccine adjuvants with ID immunization."	( High immunogenicity of nicotine vaccines obtained by intradermal delivery with safe adjuvants. Bhayana, B; Chen, X; Pentel, PR; Pravetoni, M; Wu, MX, 2012)	0.92
" The secondary aims were to evaluate the side effect profiles of lorcaserin and CP-809101 and to determine the plasma levels of lorcaserin at a dose (1 mg/kg) that reduces both food and nicotine reinforcement for comparison to plasma concentrations reported in human trials."	( Evaluation of chemically diverse 5-HT₂c receptor agonists on behaviours motivated by food and nicotine and on side effect profiles. Coen, K; de Lannoy, IA; Fletcher, PJ; Higgins, GA; Izhakova, J; Lau, W; Le, AD; Lee, DK; Silenieks, LB, 2013)	0.8
" Finally, there may be differences in the side effect profiles between lorcaserin and CP-809101, raising the possibility for tolerability differences amongst 5-HT2C agonists."	( Evaluation of chemically diverse 5-HT₂c receptor agonists on behaviours motivated by food and nicotine and on side effect profiles. Coen, K; de Lannoy, IA; Fletcher, PJ; Higgins, GA; Izhakova, J; Lau, W; Le, AD; Lee, DK; Silenieks, LB, 2013)	0.61
" Adverse events and product preferences were also reviewed."	( EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. Campagna, D; Caponnetto, P; Caruso, M; Cibella, F; Morjaria, JB; Polosa, R; Russo, C, 2013)	0.39
" A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study."	( EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. Campagna, D; Caponnetto, P; Caruso, M; Cibella, F; Morjaria, JB; Polosa, R; Russo, C, 2013)	0.39
" Secondary outcomes include adherence to e-cigarettes, self-reported adverse events, quality of life, and time to hospital admission for one among cardiovascular diseases, chronic obstructive pulmonary diseases, cancer of the lung, esophagus, larynx, oral cavity, bladder, pancreas, kidney, stomach, cervix, and myeloid leukemia."	( Multicentric cohort study on the long-term efficacy and safety of electronic cigarettes: study design and methodology. Boccia, S; Capasso, L; Cicolini, G; Di Baldassarre, A; Flacco, ME; La Vecchia, C; Manzoli, L; Mezzetti, A; Simonetti, V; Villari, P, 2013)	0.39
" The method can easily be scaled up to serve as a high-throughput screening tool to detect sublethal toxic effects of a variety of chemicals."	( Optical bioassay for measuring sublethal toxicity of insecticides in Daphnia pulex. Kashian, DR; McElmurry, SP; Pitts, DK; Savolainen, PT; Zein, MA, 2014)	0.4
" Our modest results suggest that adverse effects and accidental exposures to ECIG cartridges are unlikely to result in serious toxicity."	( Adverse effects of e-cigarette exposures. Cantrell, FL, 2014)	0.4
"In utero exposure to nicotine is associated with increased risk of numerous adverse fetal and neonatal outcomes, which suggests that it acts directly to affect placental development and the establishment of the fetomaternal circulation (FC)."	( Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies. Alfaidy, N; Benharouga, M; Feige, JJ; Garnier, V; Holloway, AC; Nicholson, CJ; Raha, S; Salomon, A; Sergent, F; Soares, MJ, 2014)	0.98
" Each drug, besides its therapeutic effect, creates the risk of adverse reactions which number and severity is not always accepted by the patient."	( [Safety of nicotine addiction treatment]. Cieślewicz, A; Jabłecka, A; Korzeniowska, K, 2013)	0.78
" Based on these premises, we analyzed and assessed the toxic impact of smoke extract from a range of tobacco products (with varying levels of nicotine) on brain microvascular endothelial cell line (hCMEC/D3), a well characterized human BBB model."	( Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe? Couraud, PO; Cucullo, L; Fofaria, N; Naik, P; Prasad, S; Romero, IA; Sajja, RK; Weksler, B, 2014)	0.8
" The purpose of this study was to determine the incidence and severity of nicotine-related adverse events in subjects with levels of cotinine, a metabolite of nicotine, that increased by >50% compared with baseline smoking in controlled clinical trials of NRT."	( Symptoms of nicotine toxicity in subjects achieving high cotinine levels during nicotine replacement therapy. Gustavsson, G; Kruse, E; Tonstad, S; Walmsley, JM; Westin, Å, 2014)	1.01
" In addition to baseline, at least 1 subsequent plasma or salivary cotinine concentration was measured, and adverse events were recorded simultaneously."	( Symptoms of nicotine toxicity in subjects achieving high cotinine levels during nicotine replacement therapy. Gustavsson, G; Kruse, E; Tonstad, S; Walmsley, JM; Westin, Å, 2014)	0.78
" Electronic cigarettes are safer than conventional cigarettes and at least as safe as other approved nicotine replacement therapies."	( Safety and efficacy of electronic cigarettes: a review. Guntur, VP; Peralta, AR, )	0.35
"Smoking during pregnancy causes many adverse pregnancy and birth outcomes."	( The SNAP trial: a randomised placebo-controlled trial of nicotine replacement therapy in pregnancy--clinical effectiveness and safety until 2 years after delivery, with economic evaluation. Britton, J; Coleman, T; Cooper, S; Dickinson, A; Essex, H; Grainge, MJ; Lewis, S; Marlow, N; Parrott, S; Taggar, J; Thornton, JG; Watts, K; Whitemore, R, 2014)	0.65
" Numbers of adverse pregnancy and birth outcomes were similar in trial groups, except for a greater number of caesarean deliveries in the NRT group."	( The SNAP trial: a randomised placebo-controlled trial of nicotine replacement therapy in pregnancy--clinical effectiveness and safety until 2 years after delivery, with economic evaluation. Britton, J; Coleman, T; Cooper, S; Dickinson, A; Essex, H; Grainge, MJ; Lewis, S; Marlow, N; Parrott, S; Taggar, J; Thornton, JG; Watts, K; Whitemore, R, 2014)	0.65
"Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories."	( The effects of acute nicotine on contextual safety discrimination. Gould, TJ; Kutlu, MG; Oliver, C, 2014)	0.72
" We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of nicotine and chlorpyrifos given individually."	( Prenatal nicotine alters the developmental neurotoxicity of postnatal chlorpyrifos directed toward cholinergic systems: better, worse, or just "different?". Seidler, FJ; Slotkin, TA, 2015)	1
" Vitamin C supplementation mitigated the harmful effects of prenatal nicotine exposure on placental hemodynamics and development, suggesting that its use may limit some of the adverse effects associated with smoking during pregnancy."	( Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates. Frias, AE; Kroenke, CD; Lo, JO; Morgan, TK; Rasanen, JP; Roberts, VH; Schabel, MC; Shoemaker, SR; Spindel, ER, 2015)	0.89
"Significant adverse effects on fibroblast growth and metabolism are observed with nicotine."	( In vitro study of the adverse effect of nicotine and physical strain on human gingival fibroblasts as a model of the healing of wounds commonly found in the military. Borke, JL; Chuang, AH; Dinos, ME; Goodin, JL; McPherson, JC; Swiec, GD, 2015)	0.91
" Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure."	( Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine. Card, J; Levin, ED; Seidler, FJ; Skavicus, S; Slotkin, TA; Stadler, A, 2015)	0.84
" This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses."	( Effects of Physalis peruviana L on Toxicity and Lung Cancer Induction by Nicotine Derived Nitrosamine Ketone in Rats. El-Kenawy, Ael-M; Elshama, SS; Osman, HE, 2015)	0.65
" Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress."	( Adverse effects of perinatal nicotine exposure on reproductive outcomes. Alfaidy, N; Barra, NG; Hardy, DB; Holloway, AC; Wong, MK, 2015)	0.71
" Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms."	( A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part B: Safety and subjective effects. Martin, C; Savioz, R; Sharma, G; Walele, T; Williams, J, 2016)	0.67
" Many toxic compounds remain in the environment after the cigarette is extinguished and accumulated in the air or on surfaces."	( Thirdhand tobacco smoke: procedures to evaluate cytotoxicity in cell cultures. Dantas, DC; Figueiró, LR; Linden, R; Ziulkoski, AL, 2016)	0.43
" Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years."	( Electronic Cigarette Toxicity. Michaels, D; Nugent, K; Orellana-Barrios, M; Payne, JD, 2017)	0.46
" Adverse events (AEs) reported by EVP subjects were more frequent during the first week after switching to the EVP."	( A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks. Bush, J; Craige, S; Cravo, AS; Martin, C; Savioz, R; Sharma, G; Walele, T, 2016)	0.43
" A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life."	( Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products. Aagaard, K; Bloch, M; Conway, K; Cosgrove, K; England, LJ; Gould, TJ; Grana, R; Hatsukami, D; Jensen, F; Kandel, D; Lanphear, B; Leslie, F; Neiderhiser, J; Pauly, JR; Rubinstein, M; Slotkin, TA; Spindel, E; Stroud, L; Wakschlag, L, 2017)	1.02
"Urban road dust can potentially have adverse effects on ecosystems if it is discharged into receiving waters."	( Causes of highway road dust toxicity to an estuarine amphipod: Evaluating the effects of nicotine. Hiki, K; Nakajima, F; Tobino, T, 2017)	0.68
" The alkaloid increases the lag time of the nucleation step and reduces the build-up of the more toxic oligomeric species in a concentration-dependent manner."	( Nicotine slows down oligomerisation of α-synuclein and ameliorates cytotoxicity in a yeast model of Parkinson's disease. Kardani, J; Roy, I; Sethi, R, 2017)	1.9
" Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous 38 amino-acid peptide with demonstrated protection against neuronal injury, trauma as well as various endogenous and exogenous toxic agents."	( PACAP Protects Against Ethanol and Nicotine Toxicity in SH-SY5Y Cells: Implications for Drinking-Smoking Co-morbidity. Csoka, AB; Getachew, B; Khundmiri, SJ; Manavalan, S; Manaye, KF; McKinley, R; Reglodi, D; Tamas, A; Tizabi, Y, 2017)	0.73
" Hence, NIC could exacerbate adverse effects of AZA while antioxidants such as resveratrol (RES) could prevent it."	( Nicotine Exposure Augments Renal Toxicity of 5-aza-cytidine Through p66shc: Prevention by Resveratrol. Arany, I; Dixit, M; Faisal, A; Hall, S, 2017)	1.9
"RES can protect the kidney from adverse effects of NIC in patients undergoing anticancer therapy."	( Nicotine Exposure Augments Renal Toxicity of 5-aza-cytidine Through p66shc: Prevention by Resveratrol. Arany, I; Dixit, M; Faisal, A; Hall, S, 2017)	1.9
"890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6."	( Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints. Elamin, A; Esposito, M; Guedj, E; Ho, J; Hoeng, J; Ivanov, NV; Kogel, U; Krishnan, S; Lebrun, S; Leroy, P; Martin, F; Nury, C; Peitsch, MC; Phillips, B; Schlage, WK; Sciuscio, D; Sharma, D; Titz, B; Vanscheeuwijck, P; Veljkovic, E; Vuillaume, G; Xiang, Y, 2017)	0.92
"Nicotine has adverse cellular and molecular effects on oral mucosa, bone, and teeth."	( Efficacy of vitamins E and C for reversing the cytotoxic effects of nicotine and cotinine. Jamshidi, M; Mansuri Torshizi, A; Rezaei Esfahrood, Z; Sotoudeh, S; Torshabi, M, 2017)	2.13
"The adverse effects of prenatal nicotine and alcohol exposure on human reproductive outcomes are a major scientific and public health concern."	( Assessment of the cerebellar neurotoxic effects of nicotine in prenatal alcohol exposure in rats. Bhattacharya, D; Bhattacharya, S; Bloemer, J; Crump, BR; Dhanasekaran, M; Fujihashi, A; Govindarajulu, M; Hightower, H; Majrashi, M; Moore, T; Ramesh, S; Suppiramaniam, V, 2018)	1.02
" Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire."	( Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting. Bush, J; Koch, A; Martin, C; O'Connell, G; Savioz, R; Walele, T, 2018)	0.69
" In conclusion, the question of whether electronic cigarettes are a safe and sufficient substitute for traditional smoking needs further investigation."	( Safety Assessment of Electronic Cigarettes and Their Relationship with Cardiovascular Disease. Hou, R; Liu, E; Wang, Z; Xing, C; Yu, Q; Zhang, G; Zhang, K, 2018)	0.48
" However, the adverse effects on child health remain largely unknown."	( The toxicity of E-cigarettes and children's respiratory health. Carlsen, KH; Lødrup Carlsen, KC; Skjerven, HO, 2018)	0.48
" Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG."	( Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. Davis, ES; Glish, GL; Keating, JE; Kochar, TK; Sassano, MF; Tarran, R; Wolfgang, MC; Zorn, BT, 2018)	0.48
" In this review, we summarize experimental findings describing increased renal risk of chronic NIC exposure and explore therapeutic interventions to alleviate adverse effects of NIC."	( Adverse effects of chronic nicotine exposure on the kidney: Potential human health implications of experimental findings . Arany, I; Dixit, M; Fülöp, T; Taylor, M, 2018)	0.78
" We compared the developmental neurotoxicity of nicotine to that of the PAH archetype, benzo[a]pyrene (BaP), and also evaluated the effects of combined exposure to assess whether PAHs might exacerbate the adverse effects of nicotine."	( The Developmental Neurotoxicity of Tobacco Smoke Can Be Mimicked by a Combination of Nicotine and Benzo[a]Pyrene: Effects on Cholinergic and Serotonergic Systems. Ko, A; Levin, ED; Seidler, FJ; Skavicus, S; Slotkin, TA, 2019)	0.99
"5% HCl + 70% ethanol, and the nicotine completely recovered via steam distillation, whereas the protein content remained unaffected in the leaves, thus making them safe for use as animal feed."	( Phytoextraction of Cd from a contaminated soil by tobacco and safe use of its metal-enriched biomass. Ge, Y; Tu, P; Wang, K; Yang, Y; Zeng, H; Zeng, Q; Zhou, X; Zou, D, 2019)	0.8
" The dose was increased weekly by adding a 21-mg patch unless participants reported adverse effects and/or did not wish to increase the dose."	( Progressive nicotine patch dosing prior to quitting smoking: feasibility, safety and effects during the pre-quit and post-quit periods. Hajek, P; McRobbie, H; Przulj, D; Wehbe, L, 2019)	0.89
"Proportion of participants progressing through each stage of dosing, adherence, adverse effects, changes in cigarette consumption, smoke intake and enjoyment of smoking during the pre-quit period; withdrawal symptoms; carbon monoxide-validated abstinence during 4 weeks post-TQD."	( Progressive nicotine patch dosing prior to quitting smoking: feasibility, safety and effects during the pre-quit and post-quit periods. Hajek, P; McRobbie, H; Przulj, D; Wehbe, L, 2019)	0.89
" Adverse effects consisted primarily of nausea and were mild and well tolerated."	( Progressive nicotine patch dosing prior to quitting smoking: feasibility, safety and effects during the pre-quit and post-quit periods. Hajek, P; McRobbie, H; Przulj, D; Wehbe, L, 2019)	0.89
" Given the known beneficial effects of NRT in treating nicotine withdrawal, reducing cravings, and promoting smoking cessation after discharge, our findings suggest that NRT is a safe and reasonable treatment option."	( Short-Term Safety of Nicotine Replacement in Smokers Hospitalized With Coronary Heart Disease. Atreya, A; Lagu, TC; Lindenauer, PK; Pack, QR; Pekow, PS; Priya, A; Rigotti, NA, 2018)	1.05
"PG attenuated elevations in ICSS thresholds induced by high-dose nicotine, which may reflect an attenuation of nicotine's acute aversive/anhedonic and/or toxic effects."	( Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats. Haave, Z; Harris, AC; LeSage, MG; Muelken, P; Smethells, JR; Swain, Y, 2018)	0.93
" The safety of NMS was assessed by measuring vital signs, visual mouth inspection, and collection of subject-reported adverse events (AEs)."	( Efficacy and Safety of a Nicotine Mouth Spray for Smoking Cessation: A Randomized, Multicenter, Controlled Study in a Naturalistic Setting. Danielsson, T; Kapikian, R; Leischow, SJ; Myers, A; Nides, M; Perfekt, R; Saunders, F; Solla, J, 2020)	0.86
"These study results demonstrate that the NMS is an effective and safe smoking cessation option for smokers motivated to quit, even in a naturalistic setting and without behavioral support."	( Efficacy and Safety of a Nicotine Mouth Spray for Smoking Cessation: A Randomized, Multicenter, Controlled Study in a Naturalistic Setting. Danielsson, T; Kapikian, R; Leischow, SJ; Myers, A; Nides, M; Perfekt, R; Saunders, F; Solla, J, 2020)	0.86
" At high concentrations, however, they can be toxic and cause neurodegenerative disorders, particularly Parkinson-like syndromes."	( Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: Implication for Parkinson's disease. Aschner, M; Csoka, AB; Getachew, B; Tizabi, Y, 2019)	1.96
" Treatment adherence and side effects, adverse and serious adverse events, and blood pressure were assessed."	( A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Carroll, AJ; Hitsman, B; Hole, A; Jao, NC; Kalhan, R; Langer, C; Leone, F; Lubitz, SF; Miele, A; Patel, J; Paul Wileyto, E; Schnoll, R; Veluz-Wilkins, A, 2019)	0.51
" There were no significant differences between treatment arms on side effects, adverse and serious adverse events, and rates of high blood pressure (P's > 0."	( A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Carroll, AJ; Hitsman, B; Hole, A; Jao, NC; Kalhan, R; Langer, C; Leone, F; Lubitz, SF; Miele, A; Patel, J; Paul Wileyto, E; Schnoll, R; Veluz-Wilkins, A, 2019)	0.51
" No adverse events were reported in the MTZ arm while 38% (n = 6) of participants reported mild adverse events in the NIC arm."	( Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults. Abdel-Rahman, S; Kearns, GL; Leeder, JS; Pearce, RE; Stancil, SL; Tyndale, RF; Vyhlidal, CA, 2019)	0.51
"Metronidazole via 2HM/MTZ performed well as a novel, safe phenotyping probe for CYP2A6 in healthy adults."	( Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults. Abdel-Rahman, S; Kearns, GL; Leeder, JS; Pearce, RE; Stancil, SL; Tyndale, RF; Vyhlidal, CA, 2019)	0.51
" Nicotine-induced lineage-specific responses and dysregulated cell-to-cell communication in EBs, shedding light on the adverse effects of nicotine on human embryonic development."	( Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development. Guo, H; Kitani, T; Lee, WH; Paik, DT; Tian, L; Wu, JC; Zhang, JZ, 2019)	1.64
", ethyl maltol) are high enough to be cytotoxic in acute in vitro assays, emphasizing the need to determine if JUUL products will lead to adverse health effects with chronic use."	( High-Nicotine Electronic Cigarette Products: Toxicity of JUUL Fluids and Aerosols Correlates Strongly with Nicotine and Some Flavor Chemical Concentrations. Luo, W; McWhirter, KJ; Omaiye, EE; Pankow, JF; Talbot, P, 2019)	1.03
" In an effort to diminish adverse developmental effects of exposure to cigarette smoking, pregnant women, and women of reproductive age, are increasingly turning to electronic nicotine delivery systems (ENDS), such as e-cigarettes, as an alternative."	( Developmental toxicity of e-cigarette aerosols. Greene, RM; Pisano, MM, 2019)	0.71
" These data further demonstrate the ability of the AFPL1 nicotine conjugate vaccine to be a safe and potential candidate for clinical use."	( Assessing the immunogenicity and toxicity of the AFPL1-conjugate nicotine vaccine using heterologous and homologous vaccination routes. Acevedo, R; Dagmar, GR; Fraleigh, NL; Le, HT; Lewicky, JD; Martel, AL; Oliva, R, 2019)	1
" There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders."	( Long-term effectiveness and safety of varenicline and nicotine replacement therapy in people with neurodevelopmental disorders: A prospective cohort study. Davies, NM; Itani, T; Jones, T; Martin, RM; Munafò, MR; Rai, D; Taylor, AE; Taylor, GMJ; Thomas, KH, 2019)	0.76
" The most common adverse events, regardless of cause, were rash (all subcategories 111 [62%] patients, maculopapular rash 72 [40%], dermatitis acneiform 22 [12%]), diarrhoea (81 [45%]), pruritus (70 [39%]), fatigue (54 [30%]), and stomatitis (54 [30%]), and were mostly grades 1-2."	( Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study. Aix, SP; Felip, E; Jonnaert, M; Kim, DW; Ko, J; Leighl, NB; Moody, SE; Pan, C; Riely, GJ; Sequist, LV; Seto, T; Tan, DS; Tan, EY; Wolf, J; Yang, JC, 2020)	0.56
"It appears that electronic cigarettes (EC) are a less harmful alternative to conventional cigarette (CC) smoking, as they generate substantially lower levels of harmful carcinogens and other toxic compounds."	( Neurotoxicity of e-cigarettes. Aschner, M; Gonçalves, FM; Ruszkiewicz, JA; Tizabi, Y; Zelikoff, JT; Zhang, Z, 2020)	0.56
"Tobacco smoking was one of the important adverse factors for congenital heart disease."	( Adverse effects of nicotine on cardiogenic differentiation from human embryonic stem cells detected by single-cell RNA sequencing. Chen, J; He, B; Li, X; Ou, Y; Tian, M; Wang, S; Zhou, C; Zhuang, J, 2020)	0.89
"Response variability across the lifespan is an important consideration in toxicology and risk assessment, and the toxic effects of drugs and chemicals during adolescence need more research."	( This is your teen brain on drugs: In search of biological factors unique to dependence toxicity in adolescence. Andersen, SL; Dow-Edwards, D; Eaton, DL; Kwan, LY; Levin, ED; Li, AA; Talpos, J; Vorhees, CV, )	0.13
" Our results show profound adverse effects of prenatal exposure of e-cigarette plus HFD in neonatal hearts that may lead to long-term adverse cardiac consequences in the adult."	( Adverse effects of fetal exposure of electronic-cigarettes and high-fat diet on male neonatal hearts. Espinoza-Derout, J; Friedman, TC; Hasan, KM; Mahata, SK; Munoz, A; Parveen, M; Shao, XM; Sinha-Hikim, AP; Tumoyan, H, 2021)	0.62
" E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry, were more toxic in HL-1 cardiomyocytes than fruit-flavored e-vapor."	( In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems. Abouassali, O; Calcul, L; Chang, M; Chidipi, B; Herweg, B; Kanithi, M; Martinez, JL; McDonald, TV; Noujaim, SF; Reiser, M; Saiz, J; Soni, R, 2021)	0.86
" Toxic chemicals and flavoring agents detected in high concentrations in the E-smoke of each flavor warrant independent evaluation for their specific role in imparting toxicity."	( Addressing the challenges of E-cigarette safety profiling by assessment of pulmonary toxicological response in bronchial and alveolar mucosa models. Ernstgård, L; Ganguly, K; Johanson, G; Koelmel, J; Lin, EZ; Nordström, A; O'Brien, F; Palmberg, L; Pollitt, KJG; Rahman, M; Ramström, M; Sompa, SI; Thimraj, TA; Upadhyay, S, 2020)	0.56
" Moreover, we describe the associated toxicity components in e-cigarettes, as well as the potential mechanism by which e-cigarettes exert toxic effects."	( Toxicity of electronic cigarettes: A general review of the origins, health hazards, and toxicity mechanisms. Cao, Y; Li, F; Li, M; Ma, X; Ma, Y; Wang, S; Wu, D; Zhang, T, 2021)	0.62
" Accordingly, the minor endpoints will include progression-free survival, response time, overall survival, and adverse events."	( Clinical efficacy and safety of nazartinib for epidermal growth factor receptor mutated non-small cell lung cancer: Study protocol for a prospective, multicenter, open-label. Cui, J; Xiao, Z; Zhang, LL, 2021)	0.62
"Electronic cigarettes continue to rise in popularity as a reportedly safe alternative to standard cigarette smoking."	( Nicotine Toxicity Secondary to Aftermarket Modifications to a Vaping Device. Bendel, GS; Hiller, HM; Ralston, A, 2022)	2.16
" Nicotine alone was not toxic in either cell culture model, while the highest tested concentration of nicotine (500 µM) caused growth inhibition of N18TG2 neuroblastoma cells."	( The Reassessed Impact of Nicotine against Neurotoxicity in Mesencephalic Dopaminergic Cell Cultures and Neuroblastoma N18TG2 Cells. Delijewski, M; Kranner, B; Krewenka, C; Moldzio, R; Radad, K, 2022)	1.93
"A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals."	( Combined Exposure to Diazinon and Nicotine Exerts a Synergistic Adverse Effect In Vitro and Disrupts Brain Development and Behaviors In Vivo. Jeong, S; Jeung, EB; Kim, K; Lee, B; Park, SM, 2021)	0.9
" Recognition that ENDS can deliver an array of chemicals and materials with known adverse consequences has spurred more careful examination of these products."	( E-Cigarettes Reexamined: Product Toxicity. Mir, H; Pipe, AL, 2022)	0.72
" Assessments will be undertaken by telephone at baseline, with three follow-up calls (two check-in calls within the first month and final follow-up at 7 months post randomization) to ascertain smoking status, treatment adherence and adverse events."	( Effectiveness, safety and cost-effectiveness of vaporized nicotine products versus nicotine replacement therapy for tobacco smoking cessation in a low-socioeconomic status Australian population: a study protocol for a randomized controlled trial. Aiken, A; Anderson, J; Barker, D; Boland, VC; Borland, R; Courtney, RJ; Farrell, M; Gartner, C; Hall, W; Howard, BC; Mattick, RP; McRobbie, H; Mendelsohn, C; Naughton, F; Petrie, D; Richmond, RL; Shakeshaft, A; Tutka, P; Zwar, N, 2022)	0.97
"Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification."	( FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study. Barker, D; Cro, S; Lingford-Hughes, AR; Mozgunov, P; Nahar, L; Paterson, LM; Paterson, S; Phillips, R; Smith, C, 2022)	0.72
" Further studies are required to determine the toxic effects of nicotine replacement therapies."	( Unintentional fatal toxicity due to nicotine chewing gum: A case report. Jang, TC; Lee, JE; Seo, YW, 2022)	1.23
" The technique provides a rapid screening approach to determine detailed immunological responses in the airways which can be linked to potentially adverse pathways and support inhalation safety assessment."	( High content analysis of in vitro alveolar macrophage responses can provide mechanistic insight for inhaled product safety assessment. Hoffman, E; Hopper, S; Hutter, V; Skamarauskas, J, 2023)	0.91
"Although electronic cigarettes (e-cigarettes) have attracted much attention due to their claimed harm-reduction effects compared with conventional cigarettes, the adverse effects of e-cigarette aerosol exposure on human health are still unclear."	( Cytotoxicity and cell injuries of flavored electronic cigarette aerosol and mainstream cigarette smoke: A comprehensive in vitro evaluation. Chen, J; Duan, K; Jiang, X; Li, M; Liu, P; Wang, L; Wang, Y; Yang, X, 2023)	0.91
" We examine how adverse events (AE) associated with EC use relative to NRTs differ, with the view that differences in AEs experienced may drive differences in use and compliance."	( Common adverse events of electronic cigarettes compared with traditional nicotine replacement therapies: A systematic review and meta-analysis. Anandan, AS; Chan, GCK; Connor, JP; Hall, WD; Leung, J; Stjepanović, D; Sun, T, 2023)	1.14
" Future work will need to quantify both the adverse and favourable effects of ECs to understand the experiential mechanisms that drive the high uptake of nicotine ECs relative to established NRTs."	( Common adverse events of electronic cigarettes compared with traditional nicotine replacement therapies: A systematic review and meta-analysis. Anandan, AS; Chan, GCK; Connor, JP; Hall, WD; Leung, J; Stjepanović, D; Sun, T, 2023)	1.34
" The incidence of death or serious adverse events was low across all trials at maximum follow-up."	( Efficacy and Safety of E-Cigarette Use for Smoking Cessation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Eisenberg, MJ; Filion, KB; Levett, JY; Prell, C; Reynier, P, 2023)	0.91
" Cytotoxicity, inflammation, and oxidative stress responses indicate that adverse effects such as local lesions in the buccal mucosa may occur after chronic product use."	( Oral nicotine pouches with an aftertaste? Part 2: in vitro toxicity in human gingival fibroblasts. Laux, P; Luch, A; Mallock-Ohnesorg, N; Pieper, E; Rinaldi, S; Schulz, T; Zimmermann, R, 2023)	1.42
" Administering compounds together partially reduced the adverse teratogenic effect induced by nicotine alone."	( Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model. Budzyńska, B; Chałas, R; Maciąg, M; Rahnama-Hezavah, M; Stachurski, P; Świątkowska, A; Świątkowski, W; Tylżanowski, P, 2023)	2.57

Pharmacokinetics

The aim of this study was to evaluate pharmacokinetic and subjective responses to a prototype nicotine pyruvate (NP) aerosol generation system. The area under the plasma concentration-time curve (AUC), mean residence time (MRT), systemic clearance (CL), distribution volume at steady state (V(ss) and terminal plasma half-life (T(1/2,beta)) of nicotine were compared between NB and NS.

Excerpt	Reference	Relevance
" Similarity in a biological half life of nicotine in dogs and humans suggested that the dog may be a better experimental model than the rate in the investigation of pharmacokinetic parameters for nicotine."	( Plasma nicotine pharmacokinetics in dogs after intravenous administration: determination by radioimmunoassay. Castro, A; Monji, N, 1979)	0.98
" The pharmacokinetic analysis revealed a significant reduction in sc plasma levels during the first half hour which is reported as the most critical period for patients experiencing nicotine intoxication."	( Animal model and pharmacokinetic interpretation of nicotine poisoning in man. Brady, ME; Cacini, W; Patterson, AJ; Ritschel, WA; Saelinger, DA, 1979)	0.7
"Physiologically based pharmacokinetic (PBPK) models have been developed describing the disposition kinetics of nicotine and its major metabolite, cotinine, in man."	( A physiologically based pharmacokinetic model for nicotine and cotinine in man. Balter, NJ; Robinson, DE; Schwartz, SL, 1992)	0.75
" Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential."	( Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Buckley, MM; Faulds, D; Palmer, KJ, 1992)	0.99
"A physiologically based pharmacokinetic (PBPK) model was developed to describe the disposition of nicotine in the Sprague-Dawley (SD) rat."	( A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. Andersen, ME; deBethizy, JD; Plowchalk, DR, 1992)	0.75
" Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks."	( Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction. Benowitz, NL, 1991)	0.6
" The nicotine pharmacokinetic parameters for Day 1 and Day 5 were similar: the mean (SD) AUC(0-24) values for Days 1 and 5 were 271."	( Pharmacokinetics of multiple daily transdermal doses of nicotine in healthy smokers. Chan, KK; John, VA; Piraino, AJ; Ross, HD, 1991)	1.04
" The plasma concentration-time profiles of nicotine and cotinine and the pharmacokinetic parameters cmax, tmax, AUC and the elimination half-life were determined under steady-state conditions."	( Pharmacokinetics of nicotine after application of a 30 cm2 nicotine patch under steady-state conditions. Caspary, S; Huber, T; Keller-Stanislawski, B; Merz, PG, 1991)	0.87
"The pharmacokinetic and pharmacodynamic characteristics of a drug are important determinants of whether users become dependent on it and of the temporal patterns of drug use."	( Pharmacokinetic considerations in understanding nicotine dependence. Benowitz, NL, 1990)	0.53
" Since pharmacokinetic factors do not account for this discrepancy, a pharmacodynamic explanation will be necessary."	( Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline. Reavill, C; Stolerman, IP; Testa, B; Walther, B, 1990)	0.54
" The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance."	( Clinical pharmacokinetics of non-opiate abused drugs. Bendayan, R; Busto, U; Sellers, EM, 1989)	0.28
"The authors propose a model of pharmacodynamic response that, when integrated with a pharmacokinetic model, allows characterization of the development of functional tolerance."	( Pharmacodynamic model of tolerance: application to nicotine. Benowitz, NL; Porchet, HC; Sheiner, LB, 1988)	0.53
" Clearance (Cl), volume of distribution (Vd), and the biological half-life (t1/2) were calculated both from the infusion study and by fitting a monoexponential model to the iv blood data of the rat."	( Constant-rate infusion of nicotine and cotinine. I. A physiological pharmacokinetic analysis of the cotinine disposition, and effects on clearance and distribution in the rat. Bondesson, U; Gabrielsson, J, 1987)	0.57
" Based upon physicochemical and pharmacokinetic principles, the oral bioavailability of nicotine would be expected to be less than 20%."	( Clinical pharmacokinetics of nicotine. Svensson, CK, 1987)	0.79
"The purpose of this investigation was to determine if the reported prolongation of barbiturate- and ethanol-induced sleeping times by nicotine in rodents are pharmacodynamic or pharmacokinetic interactions."	( Kinetics of drug action in disease states XI: effect of nicotine on the pharmacodynamics and pharmacokinetics of phenobarbital and ethanol in rats. Hisaoka, M; Levy, G, 1985)	0.72
" The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure."	( Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure. Adir, J; Rotenberg, KS, 1983)	0.79
" The absorption and elimination of nicotine, as well as the formation and elimination of its metabolites, followed first-order kinetics, and the derived pharmacokinetic parameters were similar to those observed after the intravenous administration of nicotine."	( Pharmacokinetics of nicotine in rats after single-cigarette smoke inhalation. Adir, J; Miller, RP; Rotenberg, KS, 1980)	0.86
"This randomized, crossover study compared the nicotine and cotinine pharmacokinetic parameters and plasma concentration profiles of two different nicotine transdermal products: Nicoderm (Alza, Palo Alto, CA; and Marion Merrell Dow, Kansas City, MO) and Habitrol (Basel Pharmaceuticals, Summit, NJ)."	( Comparison of the pharmacokinetics of two nicotine transdermal systems: nicoderm and habitrol. Eller, M; Gorsline, J; Gupta, SK; Okerholm, RA; Rolf, CN; Wei, G, 1995)	0.81
" Small amounts of 200 uM dopamine were pressure ejected near the tip of the recording electrode at 5-min intervals, while the peak concentration and time course of dopamine clearance were measured voltammetrically."	( Nicotine enhances dopamine clearance in rat nucleus accumbens. Gerhardt, GA; Hart, C; Ksir, C; Mellor, G, 1995)	1.73
" There was no evidence of acute pharmacodynamic tolerance, with cigarettes leading to altered feelings of anxiety/stress over the whole day of smoking."	( Acute pharmacodynamic tolerance to the subjective effects of cigarette smoking. Parrott, AC, 1994)	0.29
" The in vivo delivery rate and the pharmacokinetic properties of a recently developed transdermal nicotine system (TNS) was investigated in three separate studies."	( Transdermal nicotine substitution: pharmacokinetics of nicotine and cotinine. Bonn, R; Caspary, S; Keller-Stanislawski, B; Merz, PG; Rietbrock, N; Wolff, M, 1993)	0.88
"This study examined the effect of gender and body weight on the pharmacokinetic properties of the Nicotine Transdermal System (NTS) (Nicoderm)."	( Nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) in women and obese men compared with normal-sized men. Gorsline, J; Prather, RD; Rolf, CN; Tu, TG, 1993)	1.95
" Time to reach peak concentration (tmax), half-life (t1/2), relative degree of fluctuation (DF) in steady-state plasma nicotine and cotinine concentrations, and renal cotinine clearance were similar for all three dosages, indicating linear pharmacokinetics and no change in nicotine metabolism with increasing dose."	( Steady-state pharmacokinetics and dose relationship of nicotine delivered from Nicoderm (Nicotine Transdermal System). Dye, D; Gorsline, J; Gupta, SK; Rolf, CN, 1993)	0.74
" After a single application, mean Cmax and tmax for plasma nicotine were 12."	( Single- and multiple-dose pharmacokinetics of Nicoderm (Nicotine Transdermal System). Coen, P; Gorsline, J; Gupta, SK; Okerholm, RA; Prather, RD, 1993)	0.78
" Pharmacokinetic comparisons showed that nicotine Cmax, area under the curve (AUC)inf, and Cavg for the NTS were lower than corresponding values for controlled smoking; Cmax and Cavg values were approximately half those of smoking."	( Comparison of the nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) and half-hourly cigarette smoking. Causey, D; Gorsline, J; Gupta, SK; Hwang, SS; Rolf, CN, 1995)	0.89
"This paper presents a comprehensive overview of the pharmacokinetic parameters used from in vivo and in vitro studies that are important in order to understand the major conceptual approaches of toxicokinetics and the disposition of environmental chemicals."	( Pharmacokinetics and molecular detoxication. Berkman, CE; Cashman, JR; Lin, J; Perotti, BY, 1996)	0.29
" Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase."	( Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis. Evans, BK; Feyerabend, C; Fuller, GS; Green, JT; Newcombe, RG; Rhodes, J; Russell, MA; Sandborn, WJ; Thomas, GA, 1997)	0.62
" The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes."	( Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration. Hurt, RD; Lawson, GM; Lipsky, JJ; Mahoney, DW; Mays, DC; McKinney, JA; Offord, KP; Sandborn, WJ; Tremaine, WJ; Zins, BJ; Zinsmeister, AR, 1997)	0.83
"To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine."	( A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration. Compton, RF; Evans, BK; Green, J; Hurt, RD; Lawson, GM; Lipsky, JJ; Mahoney, DW; Mays, DC; Offord, KP; Sandborn, WJ; Sheets, AJ; Tremaine, WJ; Zins, BJ; Zinsmeister, AR, 1997)	0.79
" This is the first evidence of pharmacokinetic predisposition to environmental tobacco smoke as an etiological factor in pediatric asthma."	( Pharmacokinetic predisposition to nicotine from environmental tobacco smoke: a risk factor for pediatric asthma. Eliopoulos, C; Greenwald, M; Klein, J; Knight, JM; Koren, G, 1998)	0.58
" Until now pharmacokinetic analyses of nicotine absorption from patches have assumed a constant clearance of nicotine over 24 hr."	( Importance of chronopharmacokinetics in design and evaluation of transdermal drug delivery systems. Benowitz, N; Gries, JM; Verotta, D, 1998)	0.57
" We have previously developed a topical enema combining nicotine with a polyacrylic carbomer; pharmacokinetic parameters were similar in healthy volunteers and patients with active ulcerative colitis."	( Nicotine carbomer enemas--pharmacokinetics of a revised formulation. Evans, BK; Feyerabend, C; Green, JT; Rhodes, J; Russell, MA; Sandborn, WJ; Thomas, GA, 1998)	1.99
" The aim of this study was to develop an oral formulation of nicotine which would be slowly released in the colon over 6 h, and to examine its pharmacokinetic profile in 12 healthy volunteers, with measurements of serum nicotine and cotinine, its principal metabolite."	( An oral formulation of nicotine for release and absorption in the colon: its development and pharmacokinetics. Evans, BK; Feyerabend, C; Green, JT; Ranshaw, C; Rhodes, J; Russell, MA; Thomas, GA, 1999)	0.86
" High concentrations of topical nicotine in the colon are achieved with relatively low systemic bioavailablity-reflected by the Cmax and AUC values for nicotine."	( An oral formulation of nicotine for release and absorption in the colon: its development and pharmacokinetics. Evans, BK; Feyerabend, C; Green, JT; Ranshaw, C; Rhodes, J; Russell, MA; Thomas, GA, 1999)	0.9
" Pharmacokinetic modeling revealed a classic one-compartment model in which nicotine is absorbed into the systemic circulation by a zero-order process and eliminated by a first-order process."	( Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function. Fishbein, L; Flotte, T; Hutson, A; O'Brien, P; Stacpoole, PW; Theriaque, D, 2000)	0.79
"We compared the pharmacokinetic profiles of the highest marketed doses of three different patch systems using a crossover study design."	( A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches. Fant, RV; Henningfield, JE; Reitberg, DP; Shiffman, S; Strahs, KR, 2000)	0.52
" Drug disposition and pharmacodynamic responsiveness to nicotine may change with age, and conclusions founded on data from studies of younger populations may not apply to elderly populations."	( Pharmacokinetics of nicotine in healthy elderly people. Hansson, A; Lunell, E; Molander, L, 2001)	0.88
" Study parameters were maximal plasma concentration (Cmax), time to Cmax (tmax), and area under the plasma concentration-time curve (AUC)."	( Pharmacokinetic investigation of a nicotine sublingual tablet. Lunell, E; Molander, L, )	0.41
"The plasma nicotine profiles were similar following repeated administration of the sublingual tablet and the 2-mg nicotine chewing gum (mean Cmax 13."	( Pharmacokinetic investigation of a nicotine sublingual tablet. Lunell, E; Molander, L, )	0.8
"The pharmacokinetic profile of the nicotine 2-mg tablet was similar to that of the 2-mg nicotine chewing gum."	( Pharmacokinetic investigation of a nicotine sublingual tablet. Lunell, E; Molander, L, )	0.69
" The data suggest that pregnant women who cannot quit heavy smoking in the second trimester form a selective group with pharmacokinetic predisposition to a high rate of nicotine metabolism."	( Heavily smoking women who cannot quit in pregnancy: evidence of pharmacokinetic predisposition. Hackman, R; Kapur, B; Klein, J; Koren, G; Selby, P, 2001)	0.51
" The present study was conducted to investigate whether nicotine pretreatment via a transdermal patch alters the behavioral, physiological, and pharmacokinetic effects of an acute dose of cocaine in nondependent human volunteers."	( Nicotine alters some of cocaine's subjective effects in the absence of physiological or pharmacokinetic changes. Kouri, EM; Lukas, SE; Stull, M, )	1.82
" Dermal pharmacokinetic profiles for nicotine were obtained in all experiments and corresponded well to the values measured in previous studies on transdermal nicotine penetration."	( Application of the minimal trauma tissue biopsy to transdermal clinical pharmacokinetic studies. Brunner, M; Eichler, HG; Mayer, BX; Müller, M; Schrolnberger, C, 2001)	0.58
" The area under the plasma concentration-time curve (AUC), mean residence time (MRT), systemic clearance (CL), distribution volume at steady state (V(ss)) and terminal plasma half-life (T(1/2,beta)) of nicotine were compared between NB and NS."	( Different pharmacokinetics of nicotine following intravenous administration of nicotine base and nicotine hydrogen tartarate in rats. Chul Chung, B; Chung, SJ; Hwa Jung, B; Shim, CK, 2001)	0.79
" These differences in pharmacokinetic profiles compared with smoking may explain that some smokers still have difficulties quitting smoking even when using NRT (apart from psychological and/or social factors)."	( Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review. Le Houezec, J, 2003)	0.75
"To evaluate the pharmacokinetic characteristics of the 2-mg and 4-mg nicotine polacrilex lozenges, the following four separate studies were conducted in healthy adult smokers: (a) A single-dose, four-way crossover (replicate design) study to compare the 4-mg lozenge and the 4-mg nicotine polacrilex gum, (b) a single-dose, two-way crossover study to compare the 2-mg lozenge and the 2-mg gum, (c) a multiple-dose, four-way crossover study to compare the lozenges administered every 90 min and the gums administered every 60 min at 2- and 4-mg dose levels, and (d) a single-dose, three-way crossover study to compare the pharmacokinetic profiles of the 4-mg lozenge when administered in three different ways: (i) Used as directed, (ii) chewed and immediately swallowed, and (iii) chewed, retained in the mouth for 5 min, and then swallowed."	( Pharmacokinetics of a nicotine polacrilex lozenge. Choi, JH; Dresler, CM; Norton, MR; Strahs, KR, 2003)	0.87
" 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
"In investigating the influence of chronic cigarette smoke exposure on hypertension, we compared the pharmacodynamic effects of enforced exposure to smoke on spontaneously hypertensive rats (SHR) with those on Wistar-Kyoto (WKY) rats."	( Pharmacodynamic effects of chronic cigarette smoke exposure in spontaneously hypertensive rats. Kita, T; Kubo, K; Nakashima, T; Ohno, N; Tanaka, T; Yonetani, Y, )	0.13
" The objective of this study was to identify age- and gender-specific differences in physiological and biochemical processes that affect tissue dosimetry and integrate them into a predictive physiologically based pharmacokinetic (PBPK) life-stage model."	( Evaluation of the potential impact of age- and gender-specific pharmacokinetic differences on tissue dosimetry. Clewell, HJ; Covington, TR; Gentry, PR; Sarangapani, R; Teeguarden, JG, 2004)	0.32
" Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg."	( Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Buss, DC; Evans, BK; Feyerabend, C; Ingram, JR; Marshall, RW; Rhodes, J; Routledge, P; Thomas, GA, 2004)	2.68
" Examples are provided using coronary calcification data from the Multi-Ethnic Study of Atherosclerosis and pharmacokinetic data of a nicotine nasal spray."	( Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data. Han, C; Kronmal, R, 2004)	0.53
"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
" Cmax and AUC of nicotine increased with the surface area (Dose), and tmax, t(1/2), CL/F and percentage of dose excreted in urine were almost the same between both treatments."	( Comparison of nicotine pharmacokinetics in healthy Japanese male smokers following application of the transdermal nicotine patch and cigarette smoking. Akasaki, M; Irie, S; Kikkawa, H; Sekiguchi, K; Sobue, S, 2006)	1.03
" In addition, we found that administration of methoxsalen significantly increased the plasma half-life of nicotine (approximately doubled) and increased its area under the curve compared with saline treatment."	( Inhibition of nicotine metabolism by methoxysalen: Pharmacokinetic and pharmacological studies in mice. Damaj, MI; Martin, BR; Sellers, EM; Siu, EC; Tyndale, RF, 2007)	0.91
" However, other compounds metabolized by CYP2A6, as well as other drugs excreted via renal clearance mechanisms similar to those of nicotine, may be susceptible to significant pharmacokinetic grapefruit juice interactions."	( Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance. Benowitz, NL; Hukkanen, J; Jacob, P, 2006)	0.79
" A mechanistic population pharmacokinetic model was fitted to all data simultaneously."	( Population pharmacokinetics of nicotine and its metabolites I. Model development. Benowitz, NL; Dempsey, DA; Levi, M; Sheiner, LB, 2007)	0.63
" COT and 3HC saliva concentrations in smokers were simulated utilizing a mechanistic population pharmacokinetic model of NIC metabolism that was adapted from the one described in a companion paper."	( Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application. Benowitz, NL; Dempsey, DA; Levi, M; Sheiner, LB, 2007)	0.65
"Nicotine AUC and Cmax were higher for Copenhagen than for any other product (p<0."	( Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge. Barnett, BC; Feuer, RM; Hatsukami, DK; Kotlyar, M; Li, ZZ; Mendoza-Baumgart, MI; Pentel, PR; Smith, EA, 2007)	3.23
"Three pharmacokinetic (PK), one safety and two efficacy studies were carried out with Nicotinell lozenges."	( Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell). Callens, A; Dautzenberg, B; Kienzler, JL; Nides, M, 2007)	0.79
" 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
" We conducted a whole-genome linkage analysis to search for candidate regions influencing quantitative variation in cotinine pharmacokinetics in a large-scale pharmacokinetic study with 61 families containing 224 healthy adult participants."	( Genome-wide linkage of cotinine pharmacokinetics suggests candidate regions on chromosomes 9 and 11. Andrews, JA; Benowitz, N; Bergen, AW; He, Y; Hops, H; Lessov-Schlaggar, CN; Swan, GE; Tildesley, E; Webster, C, 2009)	0.35
" Here, it is demonstrated for the first time that the pharmacokinetic and hemodynamic effects of a nicotine patch are significantly different between smokers and nonsmokers."	( Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch. Baek, IH; Choi, JE; Kang, W; Kwon, KI; Seo, JW; Yun, HY, 2008)	0.8
" For both compounds, a substantially longer plasma half-life and a greater area under the concentration-time curve were observed for the Cyp2a5-null mice, compared with wild-type mice."	( Role of CYP2A5 in the clearance of nicotine and cotinine: insights from studies on a Cyp2a5-null mouse model. Ding, X; Humphreys, WG; Kluetzman, K; Shu, YZ; Xie, F; Zhou, X; Zhuo, X, 2010)	0.64
" Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy peak concentration and AUC in blood."	( Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats. Busby-Hjerpe, AL; Lee, S; Poet, TS; Smith, JN; Timchalk, C, 2010)	1.1
"A comparison of the 21-mg NiQuitin patch with other marketed nicotine patches reported significant differences in pharmacokinetic profiles, even among patches of the identical labeled dose strength."	( Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: a randomized, open-label, single-dose, two-way crossover study in adult smokers. Chen, LH; DeVeaugh-Geiss, AM; Durcan, MJ; Kotler, ML; Ramsay, LR, 2010)	0.88
" To determine whether any pharmacokinetic differences might be related to differences in wear time, a post hoc exploratory analysis evaluated the nicotine delivery profiles of the patches under the assumption that the 21-mg patch was removed after 16 rather than 24 hours."	( Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: a randomized, open-label, single-dose, two-way crossover study in adult smokers. Chen, LH; DeVeaugh-Geiss, AM; Durcan, MJ; Kotler, ML; Ramsay, LR, 2010)	0.84
" The primary pharmacokinetic parameter was the AUC(0-infinity), an indication of total nicotine exposure."	( Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: a randomized, open-label, single-dose, two-way crossover study in adult smokers. Chen, LH; DeVeaugh-Geiss, AM; Durcan, MJ; Kotler, ML; Ramsay, LR, 2010)	0.86
"The aim of this study was to evaluate pharmacokinetic and subjective responses to a prototype nicotine pyruvate (NP) aerosol generation system."	( Pulmonary delivery of nicotine pyruvate: sensory and pharmacokinetic characteristics. Behm, FM; Laugesen, M; Murugesan, T; Rose, JE; Turner, JE, 2010)	0.89
"The present study defined a simplified physiologically based pharmacokinetic (PBPK) model for nicotine and its primary metabolite cotinine in humans, based on metabolic parameters determined in vitro using relevant liver microsomes, coefficients derived in silico, physiological parameters derived from the literature, and an established rat PBPK model."	( Human blood concentrations of cotinine, a biomonitoring marker for tobacco smoke, extrapolated from nicotine metabolism in rats and humans and physiologically based pharmacokinetic modeling. Horiuchi, K; Kitajima, M; Murayama, N; Nagano, T; Shimizu, M; Shono, F; Takano, R; Yamazaki, H, 2010)	0.8
" For pharmacokinetic characterization of nicotine and cotinine (a major and pharmacologically less active metabolite of nicotine), a rapid ultra-performance liquid chromatography/electrospray ionization-mass spectrometry (UPLC/ESI-MS) method was developed that requires only a small amount of sample and simple pretreatment."	( Pharmacokinetic study of nicotine and its metabolite cotinine to clarify possible association between smoking and voiding dysfunction in rats using UPLC/ESI-MS. Onoue, S; Seto, Y; Yamada, S; Yamamoto, N, 2011)	0.94
" The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3."	( [Study of pharmacokinetics of nicotine in local brain by using microdialysis and stable labeled isotope]. Fu, X; Ling, JJ; Qin, ZH; Wu, XJ; Zhang, YF, 2011)	0.94
" Blood samples were collected for 12 hr to determine pharmacokinetic variables."	( Single-dose pharmacokinetics of nicotine when given with a novel mouth spray for nicotine replacement therapy. Hansson, A; Kraiczi, H; Perfekt, R, 2011)	0.65
" Pharmacokinetic modeling was performed and the two test cigarettes were assessed for bioequivalence."	( Evaluation of the effect of ammonia on nicotine pharmacokinetics using rapid arterial sampling. Barr, WH; Carter, WH; Davies, BD; Fisher, K; Garnett, WR; Gogova, M; Iyer, SS; Karnes, HT; Kobal, G; McKinney, DL; Ramakrishnan, V; Somani, AA, 2012)	0.65
"Dl-nicotine can be used as internal standard of nicotine to correcte the recovery; Stable isotopes internal standard microdialysis technology can be used for studing the whole and the local pharmacokinetic of nicotine and also provide new ideas and methods to studing the process of new drug delivery system."	( [Pharmacokinetics of nicotine in blood and brain using microdialysis and stable labelled isotope]. Fu, X; Ling, J; Wu, X, 2012)	1.32
" A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine."	( A multi-route model of nicotine-cotinine pharmacokinetics, pharmacodynamics and brain nicotinic acetylcholine receptor binding in humans. Gunawan, R; Hinderliter, PM; Housand, CJ; Smith, JN; Teeguarden, JG; Timchalk, CA, 2013)	0.98
"Administration of intra peritoneal (ip) methoxsalen significantly increased nicotine's Cmax, prolonged the plasma half-life (fourfold decrease) of nicotine, and increased its area under the curve (AUC) compared with ip vehicle treatment."	( Pharmacokinetic and pharmacodynamics studies of nicotine after oral administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor. Alsharari, SD; Damaj, MI; Siu, EC; Tyndale, RF, 2014)	0.89
" However, age-related pharmacokinetic differences may confound the interpretation of these findings."	( Nicotine pharmacokinetics in rats is altered as a function of age, impacting the interpretation of animal model data. Craig, EL; Cui, JZ; Miksys, S; Novalen, M; Tyndale, RF; Zhao, B, 2014)	1.85
" Pharmacokinetic results showed that the mean half-lives of nicotine, cotinine, nornicotine, norcotinine, nicotine-N'-oxide, cotinine-N'-oxide, trans-3'-hydroxy-cotinine, nicotine-N-glucuronide, cotinine-N-glucuronide, and trans-3'-hydroxy-cotinine-O-glucuronide in rat plasma were 63, 291, 175, 440, 251, 451, 322, 341, 488, and 516 min, respectively."	( Simultaneous determination of nicotine and its nine metabolites in rat blood utilizing microdialysis coupled with UPLC-tandem mass spectrometry for pharmacokinetic application. Hong, G; Liu, J; Lu, B; Mao, J; Sun, S; Xu, Y; Zhang, J; Zhang, Q, 2015)	0.95
" One participant had Tmax of 30 minutes."	( Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Benowitz, NL; Dempsey, DA; Havel, C; Jacob, P; St Helen, G, 2016)	1.88
" Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential."	( Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Benowitz, NL; Dempsey, DA; Havel, C; Jacob, P; St Helen, G, 2016)	2.15
" During the 7-day confinement period, blood samples were drawn for pharmacokinetic analysis."	( Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes. Haziza, C; Lama, N; Lüdicke, F; Picavet, P; Weitkunat, R, 2016)	0.71
"1 effectively delivers nicotine and achieves similar pharmacokinetic profiles to CCs."	( Comparison of the Pharmacokinetics of Nicotine Following Single and Ad Libitum Use of a Tobacco Heating System or Combustible Cigarettes. Haziza, C; Lama, N; Lüdicke, F; Picavet, P; Weitkunat, R, 2016)	1.02
"The pharmacokinetic (PK) profile of nicotine delivered by an Electronic Vapour Product (EVP) was characterised in a 2-part study in smokers."	( A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part A: Pharmacokinetics. Martin, C; Savioz, R; Sharma, G; Walele, T; Williams, J, 2016)	0.95
" The method was successfully applied to biological samples obtained from a pharmacokinetic study conducted in adult smokers to investigate heat effect on nicotine and cotinine serum levels after nicotine transdermal delivery system (TDS) application."	( A fully validated LC-MS/MS method for simultaneous determination of nicotine and its metabolite cotinine in human serum and its application to a pharmacokinetic study after using nicotine transdermal delivery systems with standard heat application in adul Abdallah, IA; Hammell, DC; Hassan, HE; Stinchcomb, AL, 2016)	0.87
"Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans."	( A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Saylor, K; Zhang, C, 2016)	0.88
" To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed."	( Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum. Hansson, A; Kraiczi, H; Rasmussen, T, 2017)	1.05
" In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables."	( Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum. Hansson, A; Kraiczi, H; Rasmussen, T, 2017)	0.71
" The objective was to develop a pharmacokinetic-pharmacodynamic (PKPD) model using nonlinear mixed effects (NLME) methods to quantitate the pharmacokinetics of three oral mecamylamine doses (10, 20 and 30 mg) and correlate the plasma concentrations to the pharmacodynamic effects on a cognitive and neurophysiologic battery of tests in healthy subjects."	( Pharmacokinetics and pharmacodynamics of oral mecamylamine - development of a nicotinic acetylcholine receptor antagonist cognitive challenge test using modelling and simulation. Alvarez-Jimenez, R; Baakman, AC; Goulooze, SC; Groeneveld, GJ; Hart, EP; Rissmann, R; Stevens, J; van Gerven, JM, 2017)	0.46
"In Study 1, Cmax (geometric mean (CV)) during a 5-minute puffing period (10 puffs, 30 seconds apart) was 13."	( E-cigarette Nicotine Delivery: Data and Learnings from Pharmacokinetic Studies. Camacho, OM; Eldridge, A; Fearon, IM; Gale, N; McAdam, K; McEwan, M; Nides, M; Proctor, CJ; Shepperd, CJ, 2017)	0.83
" Such differences must be taken into account when determining the likely behavioral impact, on smoking reduction and cessation, of nicotine delivery data and when planning e-cigarette nicotine pharmacokinetic studies."	( E-cigarette Nicotine Delivery: Data and Learnings from Pharmacokinetic Studies. Camacho, OM; Eldridge, A; Fearon, IM; Gale, N; McAdam, K; McEwan, M; Nides, M; Proctor, CJ; Shepperd, CJ, 2017)	1.04
" The organic cation transporter OCT2 rs316019 significantly increased nicotine and COT Cmax (P=0."	( Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans. Benowitz, NL; St Helen, G; Taghavi, T; Tyndale, RF, 2017)	0.93
" The pharmacokinetic characteristics were consistent between subjects, and there were no safety concerns."	( First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288. Edmonds, SA; Freedman, R; Gee, KW; Harris, J; Hogenkamp, D; Johnson, L; Johnstone, T; Kanner, R; Olincy, A; Sauer, W; Tran, M; Yoshimura, R, 2017)	0.46
" We performed a combined retrospective population pharmacokinetic analysis of 8 trials, including exposure to Tobacco Heating System and cigarettes (both inhaled), nicotine nasal spray and oral nicotine gum."	( Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis. Brossard, P; Lama, N; Lüdicke, F; Marchand, M; Merdjan, H; Weitkunat, R, 2017)	2.09
" The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis."	( Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo. Adaralegbe, A; Arutla, V; Chang, Y; Hecht, SM; Leal, J; Liu, L; Liu, X; Pentel, PR; Raleigh, M; Sokalingam, S, 2017)	1.02
" The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated."	( Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System. Brossard, P; Felber Medlin, L; Franzon, M; Laugesen, M; Lüdicke, F; Sandalic, L; Teichert, A; Wynne, C, 2018)	1.11
" These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum."	( Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability. Campbell, LR; Fant, RV; Graff, DW; Henningfield, JE; Jones, BA; Stiles, MF, 2017)	0.87
" The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch."	( Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch. Linakis, MW; Miller, EI; Roberts, JK; Rower, JE; Sherwin, CMT; Wilkins, DG, 2017)	0.91
"A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine."	( Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch. Linakis, MW; Miller, EI; Roberts, JK; Rower, JE; Sherwin, CMT; Wilkins, DG, 2017)	0.91
"This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch."	( Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch. Linakis, MW; Miller, EI; Roberts, JK; Rower, JE; Sherwin, CMT; Wilkins, DG, 2017)	0.92
" In this study, we performed IVPT studies using excised human skin (in vitro) and harmonized in vivo human serum pharmacokinetic (PK) studies to evaluate the potential in vitro-in vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine transdermal delivery systems (TDS)."	( In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application. Billington, MM; Chen, WH; El-Kamary, SS; Ghosh, P; Hammell, DC; Hassan, HE; Raney, SG; Shin, SH; Stinchcomb, AL; Thomas, S, 2018)	0.95
" Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t)."	( Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . Kaushik, A; Srivastava, R; Sukhija, M, 2018)	0.73
" Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior."	( Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . Kaushik, A; Srivastava, R; Sukhija, M, 2018)	0.73
" Nicotine pharmacokinetic studies of e-cigarettes have been performed for a number of years and are beginning to show how nicotine delivery is evolving as the products themselves evolve."	( Nicotine pharmacokinetics of electronic cigarettes: A review of the literature. Eldridge, AC; Fearon, IM; Gale, N; McEwan, M; Round, EK; Stiles, MF, 2018)	2.83
" The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers."	( Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers. Feldman, JL; Fung, D; Lee, ES; Liang, J; Liu, S; Louie, S; Mudgway, R; Pei, H; Shao, XM; Xie, XS; Zhang, J; Zhu, Y, 2018)	1.31
" Here, we evaluated the pharmacokinetic profiles and subjective effects of nicotine from two e-cigarette device platforms with varying concentrations of nicotine lactate (nicotine salt) e-liquid relative to conventional cigarettes."	( A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt formulations in US adult smokers. Graff, D; O'Connell, G; Pritchard, JD; Prue, C; Thompson, J; Verron, T; Walele, T, 2019)	0.95
" We use these data to run combined pharmacokinetic and pharmacodynamic simulations of human smoking."	( Determining the pharmacokinetics of nicotinic drugs in the endoplasmic reticulum using biosensors. Bao, H; Bera, K; Bishara, I; Borden, PM; Chapman, ER; Cohen, B; Dougherty, DA; Jeon, J; Kim, C; Lester, HA; Looger, LL; Marvin, JS; Mulcahy, MJ; Muthusamy, AK; Nichols, AL; O'Riordan, SL; Shivange, AV, 2019)	0.51
" Serum concentrations were determined using LC-MS/MS and the pharmacokinetic parameters were calculated."	( Evaluation of the impact of waterpipe tobacco smoke exposure on the activity and expression of rat hepatic CYP450: a pharmacokinetic study. Alshogran, OY; Alzoubi, KH; Khabour, OF; Magarbeh, LS; Saleh, MI, )	0.13
" This study aimed to characterize the nicotine pharmacokinetic profile of Spectrum cigarettes."	( Pharmacokinetic Profile of Spectrum Reduced Nicotine Cigarettes. Branstetter, SA; Foulds, J; Kamens, HM; Miller, CN; Muscat, JE; Nye, RT; Richie, JP; Silva, CP; Singh, N; Sipko, J; Sun, D; Trushin, N, 2020)	1.09
"This is the first study to determine the pharmacokinetic profile of Spectrum reduced nicotine content research cigarettes following an overnight abstinence."	( Pharmacokinetic Profile of Spectrum Reduced Nicotine Cigarettes. Branstetter, SA; Foulds, J; Kamens, HM; Miller, CN; Muscat, JE; Nye, RT; Richie, JP; Silva, CP; Singh, N; Sipko, J; Sun, D; Trushin, N, 2020)	1.04
" Plasma concentrations of nicotine and cotinine were measured, and pharmacokinetic parameters were estimated."	( Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers. Benowitz, NL; Dempsey, DA; Jacob, P; Liakoni, E; St Helen, G; Tyndale, RF, 2019)	1.08
" A physiologically-based pharmacokinetic (PBPK) model was created to characterize the pharmacokinetic behaviors of nicotine and its metabolites, cotinine, trans-3'-hydroxycotinine (3'-OH cotinine), and trans-3'-hydroxycotinine glucuronide (3'-OH cotinine glucuronide) for both adult and adolescent squirrel monkeys."	( Use of a physiologically-based pharmacokinetic model to explore the potential disparity in nicotine disposition between adult and adolescent nonhuman primates. Bryant, M; Chemerynski, S; Deng-Bryant, Y; Fisher, J; Gamboa da Costa, G; Goodwin, A; Jackson, K; Jacob, CC; Loukotková, L; Matazel, K; Naylor, J; Reissig, C; Yang, X, 2020)	0.99
" Several inhalation-based physiologically based pharmacokinetic (PBPK) models have been developed, but the applicability of these models for aerosols has yet to be verified."	( Bridging inhaled aerosol dosimetry to physiologically based pharmacokinetic modeling for toxicological assessment: nicotine delivery systems and beyond. Hayes, AW; Hoeng, J; Kolli, AR; Kuczaj, AK; Martin, F; Peitsch, MC, 2019)	0.72
" Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff."	( Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff. Fagerström, K; Hughes, J; Lunell, E; Pendrill, R, 2020)	1.1
" Two-compartment pharmacokinetic simulations yielded systemic drug concentrations consistent with the human pharmacokinetic data."	( Modeling Temperature-Dependent Dermal Absorption and Clearance for Transdermal and Topical Drug Applications. Ghosh, P; Hao, J; Kasting, GB; LaCount, TD; Li, SK; Raney, SG; Talattof, A; Zhang, Q, 2020)	0.56
" Population pharmacokinetic models can support exposure-response modeling and inform nicotine replacement therapy product development, but only limited model-based cross-study population pharmacokinetic analyses for nicotine replacement therapy products have been published."	( Nicotine Population Pharmacokinetics in Healthy Smokers After Intravenous, Oral, Buccal and Transdermal Administration. Hansson, AC; Olsson Gisleskog, PO; Perez Ruixo, JJ; Soons, PA; Westin, Å, 2021)	2.29
"Robust population pharmacokinetic models were developed for five nicotine replacement therapy product types and for intravenous and oral nicotine."	( Nicotine Population Pharmacokinetics in Healthy Smokers After Intravenous, Oral, Buccal and Transdermal Administration. Hansson, AC; Olsson Gisleskog, PO; Perez Ruixo, JJ; Soons, PA; Westin, Å, 2021)	2.3
"Baseline plasma and urine biomarker data were available from two smoking cessation clinical trials and one nicotine pharmacokinetic study (total N = 768)."	( Nicotine metabolite ratio: Comparison of the three urinary versions to the plasma version and nicotine clearance in three clinical studies. Addo, N; Ahluwalia, JS; Benowitz, NL; Chenoweth, MJ; Cox, LS; George, TP; Giratallah, HK; Lerman, C; Tyndale, RF, 2021)	2.28
" Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge."	( Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge. Araga, M; Armogida, M; Hamilton, A; Lai, PM, 2021)	1.07
" NMR is renowned for its straightforward data interpretation and quantitative properties, making it attractive for pharmacokinetic applications, where drug metabolism pathways, concentrations, and kinetics need to be evaluated."	( Developing Analytical Applications for Parahydrogen Hyperpolarization: Urinary Elimination Pharmacokinetics of Nicotine. Ausmees, K; Reile, I; Reimets, N; Vija, S, 2021)	0.83
"Physiologically based pharmacokinetic (PBPK) modeling can be a useful tool for characterizing nicotine pharmacokinetics (PK) from use of tobacco products."	( A comprehensive physiologically based pharmacokinetic (PBPK) model for nicotine in humans from using nicotine-containing products with different routes of exposure. Campbell, JL; Gentry, R; Gogova, M; Liu, J; McKinney, WJ; Muhammad-Kah, RS; Pithawalla, YB; Pourhashem, H; Rostami, AA; Sarkar, MA, 2022)	1.17
"The test e-cigarettes achieved similar nicotine delivery and pharmacokinetic profiles to those of the comparator cigarettes, indicating that this e-cigarette could be a potential alternative to conventional cigarettes for those adult smokers."	( Nicotine Delivery and Pharmacokinetics of an Electronic Cigarette Compared With Conventional Cigarettes in Chinese Adult Smokers: A Randomized Open-Label Crossover Clinical Study. Guan, Y; Guo, Y; Huang, M; Jiang, F; Li, S; Wang, Z; Zhong, G, 2022)	2.43
" To the best of our knowledge, this is the first study to evaluate the nicotine delivery and pharmacokinetic profile of a commercial e-cigarette brand compared with conventional cigarettes in Chinese adult smokers."	( Nicotine Delivery and Pharmacokinetics of an Electronic Cigarette Compared With Conventional Cigarettes in Chinese Adult Smokers: A Randomized Open-Label Crossover Clinical Study. Guan, Y; Guo, Y; Huang, M; Jiang, F; Li, S; Wang, Z; Zhong, G, 2022)	2.4
"Participants used their usual brand of ST (loose ST [n = 30] or portioned ST [n = 20]) during an experimental visit wherein use behavior and plasma nicotine pharmacokinetic parameters were measured following single use (first hour of the session) and ad libitum use (remaining 7 h of the session)."	( A Comparison of Use Topography and Nicotine Pharmacokinetics Among Loose and Portioned Smokeless Tobacco Users. Cartagena, C; Hull, LC; Koszowski, B; Meredith, S; Nighbor, T; Pickworth, WB; Salazar, E, 2023)	1.39
" Significant associations were observed between free nicotine content and first use Cmax (rs = ."	( A Comparison of Use Topography and Nicotine Pharmacokinetics Among Loose and Portioned Smokeless Tobacco Users. Cartagena, C; Hull, LC; Koszowski, B; Meredith, S; Nighbor, T; Pickworth, WB; Salazar, E, 2023)	1.44
" A physiologically based pharmacokinetic (PBPK) model was constructed to describe the disposition of nicotine and its major metabolite, cotinine."	( Deconvolution of Systemic Pharmacokinetics Predicts Inhaled Aerosol Dosimetry of Nicotine. Calvino-Martin, F; Hoeng, J; Kolli, AR; Kuczaj, AK; Lebrun, S; Schlage, WK; Titz, B; Vanscheeuwijck, P; Wong, ET; Xiang, Y, 2023)	1.35

Compound-Compound Interactions

Bupropion, administered alone or combined with nicotine, is presently used to treat nicotine dependence. We used brain microdialysis to study the effects of nicotine on extracellular levels of dopamine (DA) and its metabolites in the rat dorsal striatum in combination with drugs inhibiting DA uptake.

Excerpt	Reference	Relevance
"Minimum bactericidal concentrations of salicylate, nicotinaldehyde singly, and in combination with nicotinic acid, or nicotinamide were determined for Staphylococcus aureus 79 and 80, and Escherichia coli 95, at inocula of 10(7)--10(2)."	( The sensitivity of Staphylococcus aureus 79 and 80, and Escherichia coli 95 to sodium salicylate, nicotinaldehyde singly, and in combination with nicotinic acid or nicotinamide. Kaplan, D, 1979)	0.26
" If pentobarbital was the CS and d-amphetamine or nicotine sulfate the US, then after about four drug-drug pairings the pentobarbital CS produced a higher heart rate (HR) than control conditions."	( Drug-drug heart rate conditioning in rats: effective USs when pentobarbital is the CS. Reilly, S; Revusky, S, 1992)	0.54
"5, 15 and 30 ml/kg, IP) alone and in combination with ethanol (1."	( Effects of carbon monoxide in combination with behaviorally active drugs on fixed-ratio performance in the mouse. Balster, RL; Knisely, JS; Rees, DC, )	0.13
"We studied the effectiveness of chewing gum containing nicotine, in combination with group counseling, for subjects who were attempting to stop smoking."	( Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. Forchammer, H; Fryd, V; Gunnersen, AB; Hansen, M; Helsted, J; Stockner, M; Tønnesen, P, 1988)	0.92
" Each drug alone produces significant subjective and cardiovascular responses, but the effects of the two drugs in combination have rarely been examined."	( Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers. DiMarco, A; Grobe, JE; Perkins, KA; Scierka, A; Sexton, JE; Stiller, RL, 1995)	0.55
"When combined with the nicotine patch, the citric acid inhaler improved 10-week smoking abstinence over lactose inhaler."	( Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler. Behm, FM; Rose, JE; Westman, EC, 1995)	0.87
" This may be particularly important in cases in which hypotensive action is exerted by the agent used in combination with the calcium channel blocker."	( Shuttle-box avoidance behavior of mice treated with nifedipine in combination with nicotine or physostigmine. Battaglia, M; Sansone, M; Vetulani, J, )	0.36
"To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief, 1-year smoking cessation outcome, and percentage of nicotine replacement."	( Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement. Caldwell, CC; Dale, LC; Fredrickson, PA; Hurt, RD; Lauger, GG; Lee, GA; Lundberg, TG; Marŭsić, Z; Neese, LW; Offord, KP, 1994)	2
"Clinically significant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention, nurse counseling, follow-up, and relapse prevention."	( Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement. Caldwell, CC; Dale, LC; Fredrickson, PA; Hurt, RD; Lauger, GG; Lee, GA; Lundberg, TG; Marŭsić, Z; Neese, LW; Offord, KP, 1994)	1.97
" When combined with N-0923, nicotine did not further enhance its effects."	( Nicotine alone and in combination with L-DOPA methyl ester or the D(2) agonist N-0923 in MPTP-induced chronic hemiparkinsonian monkeys. Domino, EF; Ni, L; Zhang, H, 1999)	2.04
" In the current study, we examined the effects of gestational nicotine exposure, alone or in combination with ethanol exposure, on offspring immune function."	( Gestational nicotine exposure alone or in combination with ethanol down-modulates offspring immune function. Basham, KB; Basta, PV; Brust, ME; Navarro, HA; Ross, WP, 2000)	0.93
"Glucose was tested alone or in combination with two stimulant drugs, amphetamine and nicotine, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions."	( Shuttle-box avoidance learning in mice: improvement by glucose combined with stimulant drugs. Battaglia, M; Pavone, F; Sansone, M, 2000)	0.53
" This descriptive study, enrolling 86 patients who volunteered for a smoking cessation program, assesses the use of 300 mg of bupropion over a 4-week period combined with 12 weeks of nicotine patch application at doses that were lowered every 4 weeks."	( [Bupropion combined with nicotine patches in smoking cessation]. Coll, F; Lores, L; Rebasa, P; Sampablo Lauro, I, )	0.63
" Anecdotal observations with a combination of sublingual pralidoxime and ipratropium (ProBAN) suggested that these agents in combination with nicotine gum improved quit rates."	( Nicotine replacement combined with a novel compound (ProBAN) for smoking cessation: a pilot study. Balon , JW; Brosky , G; Cox , G; Leigh , R; O'Shaughnessy , D; Sears , MR; Viner , NM; Walker , C; Wilson , DM, )	1.78
"This pilot study indicated that ProBAN combined with nicotine replacement doubled the continuous sustained quit rate compared with nicotine replacement alone, with no adverse effects."	( Nicotine replacement combined with a novel compound (ProBAN) for smoking cessation: a pilot study. Balon , JW; Brosky , G; Cox , G; Leigh , R; O'Shaughnessy , D; Sears , MR; Viner , NM; Walker , C; Wilson , DM, )	1.82
" By contrast, the same drug combination treatment did not reduce the somatic signs of nicotine withdrawal indicating symptom-specific neurobiological abnormalities."	( Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats. Harrison, AA; Liem, YT; Markou, A, 2001)	0.75
"Nortriptyline combined with transdermal nicotine resulted in an increased cessation rate with little effect on withdrawal symptoms."	( A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation. Fryer, GE; Kick, S; Miyoshi, T; Prochazka, AV; Steinbrunn, C, 2004)	0.83
" The nicotinic agonists were given acutely and repeatedly either alone or in combination with a dopamine uptake inhibitor, nomifensine."	( Comparison of the effects of nicotine and epibatidine given in combination with nomifensine on rotational behaviour in rats. Ahtee, L; Janhunen, S; Tuominen, RK, 2005)	0.62
" We used brain microdialysis to study the effects of nicotine on extracellular levels of dopamine (DA) and its metabolites in the rat dorsal striatum in combination with drugs inhibiting either DA uptake (nomifensine), catechol-O-methyltransferase (COMT; tolcapone), monoamine oxidase B (MAO-B; selegiline) or DA receptors (haloperidol)."	( The effect of nicotine in combination with various dopaminergic drugs on nigrostriatal dopamine in rats. Ahtee, L; Janhunen, S; Kaakkola, S; Mielikäinen, P; Paldánius, P; Tuominen, RK, 2005)	0.94
"A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted."	( A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Allen, TM; Creeden, CL; Dudas, MM; Feingold, A; George, TP; Jatlow, PI; Potenza, MN; Sacco, KA; Vessicchio, JC; Weinberger, AH, 2008)	0.59
"Bupropion, administered alone or combined with nicotine, is presently used to treat nicotine dependence."	( Effects of bupropion, alone or coadministered with nicotine, on social behavior in mice. Carrasco, C; Gómez, C; Redolat, R, 2008)	0.85
"05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT)."	( A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation. Albino, AP; Becker, KM; Rose, JE, 2008)	1.14
"To investigate the effects of nicotine in combination with okadaic acid (OA) or taxol on bovine oocyte maturation and subsequent embryonic development."	( Nicotine combined with okadaic acid or taxol adversely affects bovine oocyte maturation and subsequent embryo development. Bunch, TD; Li, GP; Liu, Y; Sessions, BR; White, KL; Yang, S, 2009)	2.08
"Oocyte maturation and subsequent embryo development in the presence of nicotine in combination with okadaic acid and taxol."	( Nicotine combined with okadaic acid or taxol adversely affects bovine oocyte maturation and subsequent embryo development. Bunch, TD; Li, GP; Liu, Y; Sessions, BR; White, KL; Yang, S, 2009)	2.03
"05 micromol/L) did not affect oocyte haploid composition; however, taxol alone or combined with nicotine caused a decrease in haploid composition compared with control."	( Nicotine combined with okadaic acid or taxol adversely affects bovine oocyte maturation and subsequent embryo development. Bunch, TD; Li, GP; Liu, Y; Sessions, BR; White, KL; Yang, S, 2009)	2.01
" Isolated and combined with EMR effects of nicotine (10(-4)-10(-15) mol/l) and antimicrobial drug metronidazole (10(-5), 10(-8), 10(-9) mol/l) were investigated."	( [Biological effects of electromagnetic radiation of extremely high frequencies combined with physiologically active compounds]. Denisova, SA; Kuznetsov, PE; Rogacheva, SM; Shul'gin, SV; Somov, AIu, )	0.39
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
") treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0."	( [Chronic administration of RJR-2403 in combination with low-dose of 17beta-estradiol corrects passive avoidance learning in ovariectomized rats]. Fedotova, IuO; Sapronov, NS, 2013)	0.39
"In this paper, we present for the first time the use of high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy combined with chemometrics as an alternative tool for the characterization of tobacco products from different commercial international brands as well as for the identification of counterfeits."	( HRMAS NMR spectroscopy combined with chemometrics as an alternative analytical tool to control cigarette authenticity. Caldarelli, S; Campredon, M; Shintu, L, 2013)	0.39
" We hypothesize that nicotine when combined with a high-fat diet (HFD) can also cause ectopic lipid accumulation in skeletal muscle, similar to recently observed hepatic steatosis."	( Nicotine in combination with a high-fat diet causes intramyocellular mitochondrial abnormalities in male mice. Friedman, TC; Ivey, R; Lee, D; Shin, CS; Sinha-Hikim, AP; Sinha-Hikim, I, 2014)	2.16
" The aims of the present study were therefore to determine whether norharmane, a tobacco constituent and monoamine oxidase inhibitor, is self-administered alone and/or in combination with nicotine, and to evaluate the neural mechanisms underlying acquisition of self-administration of the two drugs."	( Reinforcing and neural activating effects of norharmane, a non-nicotine tobacco constituent, alone and in combination with nicotine. Arnold, MM; Belluzzi, JD; Leslie, FM; Loughlin, SE, 2014)	0.83
"Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months."	( Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. Abdool-Gaffar, MS; Bateman, ED; Bruning, A; Emanuel, S; Esterhuizen, TM; Irusen, EM; Koegelenberg, CF; Noor, F; O'Brien, JA; Smith, C; van Zyl-Smit, RN, 2014)	0.67
" The objective of this study was to explore the wound healing effects of nicotine in combination with collagen scaffold using skin defects in rabbit."	( Exploration of the wound healing effect of topical administration of nicotine in combination with collagen scaffold in a rabbit model. Masuoka, H; Morimoto, N; Ogino, S; Sakamoto, M; Suzuki, S, 2016)	0.9
"To develop a method for the determination of nicotine and cotinine in urine samples by dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography-mass spectrometry (DLLME-GC/MS)."	( [Determination of Nicotine and Cotinine in Urine by Dispersive Liquid-Liquid Microextraction Combined with Gas Chromatography-Mass Spectrometry]. Lei, L; Li, Y; Zheng, QY; Zhu, J; Zou, XL, 2016)	1.03
" The present study used a conditioned avoidance response (CAR) test (a behavioral test of antipsychotic effect) and examined the specific drug-drug interactions between nicotine and haloperidol or clozapine."	( A drug-drug conditioning paradigm reveals multiple antipsychotic-nicotine interactions. Feng, M; Li, M; Sparkman, NL; Sui, N, 2017)	0.89
"In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model."	( Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis. Battaglia, A; Nguyen, T, 2017)	1.06
"1 times more quickly in combination with TOB than in combination with saline (p < 0."	( Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis. Battaglia, A; Nguyen, T, 2017)	0.76
" Accordingly, the exposure to fractionated-LDR combined with EA may be a promising candidate for treating hormonal changes and testicular toxicity caused by nicotine."	( Ameliorative effect of fractionated low-dose gamma radiation in combination with ellagic acid on nicotine-induced hormonal changes and testicular toxicity in rats. Abdel-Naby, DH; Ashoub, AH; El-Ghazaly, MA; Kenawy, SA; Safar, MM, 2021)	1.04
"We are the first to study a drug-drug discrimination using the DGT task."	( Understanding the stimulus effects of nicotine and bupropion in a drug-drug discriminated goal-tracking task. Barrett, ST; Bevins, RA; Finkner, AP; Huynh, YW; Moran, AE; Selleck, C; Thompson, A, 2022)	0.99
" This study aims to test the potential feasibility of a quit smoking strategy (abrupt verses gradual cessation) in combination with vaporised nicotine products among people in AOD treatment."	( A pilot randomised controlled trial of abrupt versus gradual smoking cessation in combination with vaporised nicotine products for people receiving alcohol and other drug treatment. Baker, A; Bonevski, B; Borland, R; Clapham, M; Dunlop, A; Gartner, C; Guillaumier, A; Lum, A; Robinson, M; Skelton, E, 2022)	1.13

Bioavailability

The absolute bioavailability of nicotine administered nasally, as drops to the nasal conchae and nasal septum, and as a nasal spray has been studied in eight healthy volunteers. The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers.

Excerpt	Reference	Relevance
" Although plasma nicotine levels equivalent to those following cigarette smoking may be obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking."	( Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Cole, PV; Feyerabend, C; Russell, MA, 1976)	1.05
" Circulating levels of norepinephrine and epinephrine increase, and the bioavailability of dopamine is altered as well."	( Nicotine and the central nervous system: biobehavioral effects of cigarette smoking. Pomerleau, OF, 1992)	1.73
" As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine."	( Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption. Benowitz, NL; Jacob, P; Johansson, CJ; Olsson, P, 1992)	0.87
"The absolute bioavailability of nicotine administered nasally, as drops to the nasal conchae and nasal septum, and as a nasal spray, has been studied in eight healthy volunteers."	( Absolute bioavailability of nicotine applied to different nasal regions. Bende, M; Carlsson, T; Gunnarsson, PO; Johansson, CJ; Olsson, P, 1991)	0.86
"A stable isotope-labeled drug method was used to determine the absolute bioavailability and absorption kinetics of a transdermal nicotine-delivery system (TTS)."	( Stable isotope method for studying transdermal drug absorption: the nicotine patch. Benowitz, NL; Chan, K; Denaro, CP; Jacob, P, 1991)	0.72
"The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules."	( Stable isotope studies of nicotine kinetics and bioavailability. Benowitz, NL; Denaro, C; Jacob, P; Jenkins, R, 1991)	0.83
" The evidence suggests that by altering the bioavailability of the above-listed neuroregulators, nicotine serves as a pharmacological "coping response", providing immediate though temporary improvement in affect or performance in response to environmental demands."	( Neuroregulatory effects of nicotine. Pomerleau, OF; Rosecrans, J, 1989)	0.79
" The analytical methods were set up to study the pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administrations of different doses of transdermal nicotine systems."	( High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine. Dubois, JP; Parisot, C; Sandrenan, N; Sioufi, A, 1989)	0.74
" Eight of them had undergone portacaval anastomosis (PCA) to increase bioavailability of nicotine by preventing liver first-pass."	( Failure of behavioral dependence induction and oral nicotine bioavailability in rats. Cohen, C; Le Houezec, J; Martin, C; Molimard, R, 1989)	0.75
" Previously reported methodology for determining nicotine bioavailability has been improved by using stable isotope-labeled nicotine administered intravenously."	( Recent studies of nicotine metabolism in humans. Benowitz, NL; Jacob, P; Shulgin, AT, 1988)	0.86
" Based upon physicochemical and pharmacokinetic principles, the oral bioavailability of nicotine would be expected to be less than 20%."	( Clinical pharmacokinetics of nicotine. Svensson, CK, 1987)	0.79
" In contrast, the rate of absorption from snuff was extremely rapid."	( A new age for snuff? Feyerabend, C; Jarvis, MJ; Russell, MA, 1980)	0.26
" Because nicotine alters the bioavailability of several behaviorally active neuroregulators, including acetylcholine, norepinephrine, dopamine, beta-endorphin, and vasopressin, we propose that nicotine is "used" by smokers to produce temporary improvements in performance or affect."	( Neuroregulators and the reinforcement of smoking: towards a biobehavioral explanation. Pomerleau, CS; Pomerleau, OF, 1984)	0.68
" As a conclusion, it is suggested that altered sensitivity of brain tissue rather than changes in bioavailability must explain variations in dose-response relationship which are frequently believed to be seen when fentanyl is used in patients with chronic drug administration."	( [Biotransformation of fentanyl. III. Effect of chronic drug exposure on the distribution, metabolism and excretion in the rat]. Brandt, K; Daub, D; Hunger, L; Lehmann, KA, 1983)	0.27
" Owing partly to the slower rate of absorption of nicotine through the buccal mucosa, however, it does not reproduce the pleasure of cigarette smoking."	( Clinical use of nicotine chewing-gum. Jarvis, MJ; Raw, M; Russell, MA, 1980)	0.86
"The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria."	( Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant. Andersson, M; Lunell, E; Molander, L, 1995)	0.87
" The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml."	( A clinical pharmacological study of subcutaneous nicotine. Benowitz, NL; Jacob, P; Le Houezec, J, 1993)	0.54
" The mean (95% confidence interval [CI]) absolute bioavailability of nicotine was 51 (95% CI, 40 to 65) and 56 (95% CI, 47 to 67) when the buccal and pulmonary techniques were used, respectively."	( Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler. Andersson, SB; Kuylenstierna, F; Lunell, E; Molander, L, 1996)	0.79
" The profiles of S-4, its N-methyl analogue, and the corresponding enantiomers across several measures of cholinergic channel function in vitro and in vivo are presented, together with in vitro metabolism and in vivo bioavailability data."	( Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties. Anderson, DJ; Arneric, SP; Brioni, JD; Buccafusco, JJ; Buckley, MJ; Decker, MW; Donnelly-Roberts, DL; Garvey, DS; Gunn, DE; Holladay, MW; Lin, NH; Marsh, KG; Prendergast, MA; Rodrigues, AD; Ryther, KB; Sullivan, JP; Williams, M, 1997)	0.3
" This study also validates a recently proposed method for estimating absolute bioavailability of a drug using drug and metabolite pharmacokinetic data, and presents novel data on plasma levels of the metabolite trans-3'-hydroxycotinine in people."	( Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking. Benowitz, NL; Jacob, P; Zevin, S, 1997)	0.6
" The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes."	( Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration. Hurt, RD; Lawson, GM; Lipsky, JJ; Mahoney, DW; Mays, DC; McKinney, JA; Offord, KP; Sandborn, WJ; Tremaine, WJ; Zins, BJ; Zinsmeister, AR, 1997)	0.83
"ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride], a novel ligand at neuronal nicotinic acetylcholine receptors with reduced adverse effects and improved oral bioavailability relative to (-)-nicotine, was tested in a variety of cognitive tests in rats and monkeys."	( ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys. Arneric, SP; Bannon, AW; Brioni, JD; Buccafusco, JJ; Curzon, P; Daanen, JF; Decker, MW; Gunther, KL; Holladay, MW; Jackson, WJ; Li, Y; Lin, NH; Prendergast, MA, 1997)	0.48
"To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine."	( A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration. Compton, RF; Evans, BK; Green, J; Hurt, RD; Lawson, GM; Lipsky, JJ; Mahoney, DW; Mays, DC; Offord, KP; Sandborn, WJ; Sheets, AJ; Tremaine, WJ; Zins, BJ; Zinsmeister, AR, 1997)	0.79
" This reduction in bioavailability appears to be a result of first-pass hepatic metabolism rather than poor mucosal absorption of nicotine."	( A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration. Compton, RF; Evans, BK; Green, J; Hurt, RD; Lawson, GM; Lipsky, JJ; Mahoney, DW; Mays, DC; Offord, KP; Sandborn, WJ; Sheets, AJ; Tremaine, WJ; Zins, BJ; Zinsmeister, AR, 1997)	0.77
" This method has been used for determination of nicotine bioavailability from new, low-dosage, nicotine chewing gum strips."	( Rapid solid-phase extraction method for automated gas chromatographic-mass spectrometric determination of nicotine in plasma. Davoli, E; Diomede, L; Fanelli, R; Salmona, M; Stramare, L, 1998)	0.77
" The amount of nicotine absorbed and the rate of absorption were related to the pH of the snuff product in aqueous suspension."	( Pharmacokinetics and pharmacodynamics of moist snuff in humans. Fant, RV; Henningfield, JE; Nelson, RA; Pickworth, WB, 1999)	0.66
"Oral nicotine administration failed to consistently increase GG muscle activation which may be a problem of local bioavailability of nicotine in the muscle."	( The influence of a transmucosal cholinergic agonist on pharyngeal muscle activity. Chajek-Shaul, T; Edwards, JK; Slamowitz, DI; White, DP, 2000)	0.82
"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
" These results suggest a time and biphasic dose effect of nicotine treatment on endothelium-dependent responses that may be related to bioavailability of NO."	( Time and dose effect of transdermal nicotine on endothelial function. Bonde, S; Boston, US; Clouse, WD; Hurt, RD; Miller, VM; Rud, KS; Severson, SR; Tonnessen, BH, 2000)	0.83
"05), mimicking the effect of an apparent decrease in bioavailability of endogenous NO."	( Chronic nicotine alters NO signaling of Ca(2+) channels in cerebral arterioles. Gerzanich, V; Simard, JM; West, GA; Zhang, F, 2001)	0.74
" Because nicotine was postulated to be a beneficial component of tobacco smoke for ulcerative colitis, various formulations of nicotine have been developed to improve the local bioavailability within the gastrointestinal tissue."	( Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. Fukada, A; Inui, K; Saito, H, 2002)	1.04
" The use of disposition functions obtained from venous data may lead to erroneous estimation of the rates of entry into the circulation and systemic bioavailability for many drugs."	( Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum. Benowitz, N; Gourlay, SG; Gries, JM; Pitsiu, M; Verotta, D, 2002)	0.73
" Pempidine is well absorbed from the gastro-intestinal tract as judged by (a) the low ratio (6."	( Pharmacological properties of pempidine (1:2:2:6:6-pentamethylpiperidine), a new ganglion-blocking compound. CORNE, SJ; EDGE, ND, 1958)	0.24
" Furthermore, the compounds are tertiary amines, implying some advantages in terms of bioavailability pertinent to future in vivo pharmacological studies."	( Carbamoylcholine homologs: novel and potent agonists at neuronal nicotinic acetylcholine receptors. Bräuner-Osborne, H; Falch, E; Frølund, B; Jensen, AA; Krogsgaard-Larsen, P; Mikkelsen, I, 2003)	0.32
" 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
" Potent and specific inhibitors of the CYP2A6 enzyme can be used in the future to increase nicotine bioavailability and thus make oral nicotine administration feasible in smoking cessation therapy."	( Quantitative structure-activity relationship analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme. Juvonen, RO; Poso, A; Rahnasto, M; Raunio, H; Wittekindt, C, 2005)	0.78
", shorter t(1/2) and higher c(max)) after ammoniation is, however, predominantly due to the higher concentration of nicotine in the smoke, rather than to an increase in the absorption rate of free-base nicotine in the respiratory tract."	( Significance of ammonium compounds on nicotine exposure to cigarette smokers. Opperhuizen, A; Rambali, B; van Amsterdam, JG; Vleeming, W; Willems, EW, 2006)	0.81
" The brain bioavailability of TC-2559 and its effects on the spontaneous firing and bursting properties of the dopaminergic (DAergic) neurones recorded extracellularly in the ventral tegmental area (VTA) were studied following systemic administration in anaesthetised rats."	( TC-2559 excites dopaminergic neurones in the ventral tegmental area by stimulating alpha4beta2-like nicotinic acetylcholine receptors in anaesthetised rats. Lodge, D; Miles, CP; Sherwood, JL; Wang, Y; Whiffin, G, 2006)	0.33
"991 microg/ml), a nicotine absorption rate equivalent to smoking 10 cigarettes/day (95% CI = 7-13 cigarettes/day)."	( Waterpipe smoking and nicotine exposure: a review of the current evidence. Job, J; Montgomery, S; Neergaard, J; Singh, P, 2007)	0.99
" Although the exact pathophysiology of cigarette smoking has not been unveiled, cigarette smoking causes injury to the vascular endothelium, produces superoxide anions, reduces production and bioavailability of nitric oxide (NO), increases production and release of endothelin, causes endothelial dysfunction, thrombosis, atherosclerosis, infarction, coronary artery disease (CAD), stroke and death."	( Structural and functional alteration of blood vessels caused by cigarette smoking: an overview of molecular mechanisms. Laher, I; Rahman, MM, 2007)	0.34
"A complete and rigorous review is presented of the possible effect(s) of ammonia on the exposure, deposition and retention of nicotine during smoking and the bioavailability of nicotine to the smoker."	( The possible role of ammonia toxicity on the exposure, deposition, retention, and the bioavailability of nicotine during smoking. Carchman, RA; Seeman, JI, 2008)	0.77
" These variations can change its absorption rate and delivery to the brain."	( Particle size distribution of nicotine in mainstream smoke from 2R4F, Marlboro Medium, and Quest1 cigarettes under different puffing regimens. Dunn-Rankin, D; Gowadia, N; Oldham, MJ, 2009)	0.64
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
"To compare the absorption rate of nicotine in volunteer blood, and determine the clinical trial on smoking cessation."	( The bioequivalent and effect of nicotine formulation gum on smoking cessation. Chutrthong, W; Tundulawessa, K; Tundulawessa, Y; Yongchaiyud, P, 2010)	0.92
"The absorption rate of nicotine in volunteers' blood Nicomild-2 and Nicorette at 0, 15, 30, 40 minutes were 0, 51."	( The bioequivalent and effect of nicotine formulation gum on smoking cessation. Chutrthong, W; Tundulawessa, K; Tundulawessa, Y; Yongchaiyud, P, 2010)	0.95
" Oral bioavailability was improved by using syringe feeding with donepezil but not galantamine."	( Alternative method of oral dosing for rats. Atcha, Z; Aw, CC; Browne, ER; Goh, CW; Lim, JS; Neo, AH; Pemberton, DJ; Rourke, C, 2010)	0.36
" It is widely accepted that NO bioavailability decrease is the majority reason."	( Asymmetric dimethylarginine: a novel biomarker of gastric mucosal injury? Hu, CP; Li, FJ; Zhang, Z; Zou, YY, 2011)	0.37
" Our results suggest that inhibiting nicotine metabolism can be used to dramatically enhance nicotine's bioavailability and its resulting pharmacology, which further supports this inhibitory approach for clinical development of an oral nicotine replacement therapy."	( Pharmacokinetic and pharmacodynamics studies of nicotine after oral administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor. Alsharari, SD; Damaj, MI; Siu, EC; Tyndale, RF, 2014)	0.93
" The results obtained from this study demonstrate that nanotization of nicotine improves neuroprotective efficacy by enhancing its bioavailability and subsequent modulation in the indicators of oxidative stress and apoptosis."	( Nicotine-encapsulated poly(lactic-co-glycolic) acid nanoparticles improve neuroprotective efficacy against MPTP-induced parkinsonism. Agarwal, S; Bhatnagar, P; Chaturvedi, RK; Chauhan, LKS; Gupta, KC; Kumar, P; Patel, DK; Singh, MP; Singhal, NK; Tiwari, MN; Tiwari, SK, 2013)	2.07
" In this study, the bioavailability of 4-O-methylhonokiol isolated from Magnolia officinalis was first demonstrated in the mouse embryos exposed to nicotine using a whole embryo culture system."	( 4-O-methylhonokiol inhibits serious embryo anomalies caused by nicotine via modulations of oxidative stress, apoptosis, and inflammation. Baek, IJ; Hong, JT; Jeong, J; Lee, BJ; Lee, JK; Lin, C; Nam, SY; Yon, JM; Yun, YW, 2014)	0.84
" In vivo, RO5126946 is orally bioavailable and brain-penetrant and improves associative learning in a scopolamine-induced deficit model of fear conditioning in rats."	( Characterization of RO5126946, a Novel α7 nicotinic acetylcholine receptor-positive allosteric modulator. Bertrand, D; Brameld, K; Button, DC; Hirakawa, R; Knoflach, F; Maag, H; Milla, ME; Misner, D; Sahdeo, S; Santarelli, L; Tombaugh, GC; Wallace, T, 2014)	0.4
"0W/kg) for 4, 6 and 8h; the whole body specific energy absorption rate (SAR) of the embryos was calculated."	( The effect of 900 and 1800 MHz GSM-like radiofrequency irradiation and nicotine sulfate administration on the embryonic development of Xenopus laevis. Akillioglu, K; Binokay, S; Boga, A; Demirhan, O; Emre, M; Sertdemir, Y, 2015)	0.65
" It is highly plausible that ENDS, which are, as of today, consumer products and not health products, deliver nicotine with a good bioavailability and could, if largely used, help to reduce smoking prevalence."	( [Electronic cigarettes: A therapeutic tool, a social phenomenon or a business?]. Berlin, I, 2015)	0.63
" This may indicate lower bioavailability of nicotine from the e-cigarette or an additional effect of other substances present in cigarette smoke but absent in an e-cigarette aerosol."	( Influence of inhaled nicotine source on arterial stiffness. Bartoń, A; Kośmider, L; Koszowski, B; Sobczak, A; Szołtysek-Bołdys, I; Zielińska-Danch, W, 2014)	0.98
" This work is aimed at theoretical determination of physicochemical parameters that affect the bioavailability of cytisine."	( Cytisine basicity, solvation, logP, and logD theoretical determination as tool for bioavailability prediction. Grudzień, M; Mazurek, AP; Pieńko, T; Taciak, PP, 2016)	0.43
" Bioavailability was product-specific, decreased with increasing nicotine ISO yield, and increased with increasing body weight."	( Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis. Brossard, P; Lama, N; Lüdicke, F; Marchand, M; Merdjan, H; Weitkunat, R, 2017)	2.14
" The nicotine form affects the bioavailability and delivery of nicotine from inhaled products."	( Carboxylate Counteranions in Electronic Cigarette Liquids: Influence on Nicotine Emissions. El-Hage, R; El-Hellani, A; Saliba, NA; Salman, R; Shihadeh, A; Talih, S, 2017)	1.2
"The in vitro permeation test (IVPT) has been widely used to characterize the bioavailability (BA) of compounds applied on the skin."	( In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application. Billington, MM; Chen, WH; El-Kamary, SS; Ghosh, P; Hammell, DC; Hassan, HE; Raney, SG; Shin, SH; Stinchcomb, AL; Thomas, S, 2018)	0.76
" The absorption rate of nicotine gum is relatively quick and absorbed at a constant rate."	( Nicotine Gum as a Therapeutic Approach for Low Blood Pressure in Parkinson's Disease: A Randomized Pilot Study. DiFrancisco-Donoghue, J; Jung, MK; Leder, A, 2019)	2.26
" The clinical implication of native curcumin is hindered in the target cells due to its low aqueous solubility, poor bioavailability and poor pharmacokinetics."	( Potential amelioration of nicotine-induced toxicity by nanocurcumin. Chattopadhyay, B; Chattopadhyay, K; Mukhopadhyay, S; Samanta, A, 2018)	0.78
" The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung."	( The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product. Halquist, MS; Kosmider, L; Mulder, HA; Patterson, JL; Peace, MR; Poklis, A; Poklis, JL; Turner, JBM, 2019)	0.51
" Modelling repeated-dose oral and buccal administrations required a time-dependent increase in clearance or decrease in bioavailability to describe the data adequately."	( Nicotine Population Pharmacokinetics in Healthy Smokers After Intravenous, Oral, Buccal and Transdermal Administration. Hansson, AC; Olsson Gisleskog, PO; Perez Ruixo, JJ; Soons, PA; Westin, Å, 2021)	2.06
" Minimal or no significant effect of other compounds may have been due to low bioavailability of these compounds in the brain, which is supported by the in silico prediction of blood-brain barrier permeability."	( Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish. Alijevic, O; Alzualde, A; de Mendoza, JH; Frentzel, S; Hoeng, J; Iturria, I; Jaka, O; Koshibu, K; Latino, DARS; Peitsch, MC; Pospisil, P, 2021)	0.62
" Compound 5k also showed considerable bioavailability in SD mice."	( Novel 1,3,5-triazine-nicotinohydrazide derivatives induce cell arrest and apoptosis in osteosarcoma cancer cells and inhibit osteosarcoma in a patient-derived orthotopic xenograft mouse model. Gong, Z; Su, Q; Tian, Z; Xu, B, 2022)	0.72
"Nicotine absorption rate influences tobacco products' addictiveness."	( The pH of Smokeless Tobacco Determines Nicotine Buccal Absorption: Results of a Randomized Crossover Trial. Mishina, E; Paredes, A; Pickworth, WB; Viray, L; Wilhelm, J, 2022)	2.43
"The baseline-adjusted maximum nicotine concentration (Cmax-BL), time-to-peak nicotine concentration (Tmax), and nicotine absorption rate (Cmax-BL divided by Tmax) were found to be similar for the e-cigarette versus those of conventional cigarettes (p > ."	( Nicotine Delivery and Pharmacokinetics of an Electronic Cigarette Compared With Conventional Cigarettes in Chinese Adult Smokers: A Randomized Open-Label Crossover Clinical Study. Guan, Y; Guo, Y; Huang, M; Jiang, F; Li, S; Wang, Z; Zhong, G, 2022)	2.45
" Oral nicotine bioavailability from moist snuff smokeless tobacco (ST) is influenced by nicotine content, pH, flavors, and tobacco cut."	( Formulation of smokeless tobacco products with a wide range of pH to study nicotine pharmacokinetics and pharmacodynamics. Hoag, SW; Hollenbeck, G; Koszowski, B; Mishina, EV; Pickworth, WB; Viray, L; Wang, F, 2022)	1.43
"The addition of protonating acids to e-cigarette liquid formulations (e-liquids) enhances nicotine bioavailability in e-cigarette use."	( Assessing the impact of protonating acid combinations in e-cigarette liquids: a randomised, crossover study on nicotine pharmacokinetics. Baxter-Wright, S; Ebajemito, J; Frosina, J; Hardie, G; McEwan, M; Taluskie, K; Thissen, J, 2023)	1.34

Dosage Studied

Tolerance to nicotine's disruptive effects on operant responding develops rapidly over a 14-36 day repeated dosing period in both rats and mice. Both in vivo and in vitro methods demonstrated a leftward shift of the dose-response curve for nicotine in denervated hearts, indicative of denervation hypersensitivity.

Excerpt	Relevance	Reference
"In 6-day pregnant New Zealand White rabbits dosed intravenously with 3H-nicotine, the 3H-activity in the uterine fluid was approximately 5 to 11 times greater than that in the plasma at the corresponding times; 3H-nicotine itself accounted for most of this radioactivity."	( Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit. Dames, NM; Fabro, S; McLachlan, JA; Sieber, SM, 1976)	0.83
" A dose-response correlation was indicated."	( Effect of nicotine on gastric acid secretion: evidence of electrogenic pump theory. Ando, M; Dinno, FH; Dinno, MA; Huang, KC; Rehm, WS, 1977)	0.66
"1--1000 microgram) administered into the inferior mesenteric artery to reach the mesenteric ganglion induced a dose-dependent rise in perfusion pressure and this dose-response curve was shifted to the right by C6 or atropine."	( In vivo direct effects of cholinergic agents on the inferior mesenteric and cardiac ganglia with relation to their receptors in the dog. Furukawa, T; Ichimasa, S; Kamiya, H; Kushiku, K, 1979)	0.26
" Flexible dosage dictated by individual needs would probably lower the incidence of side effects and might secure closer approximation to smoking concentrations of plasma nicotine."	( Nicotine chewing gum as a substitute for smoking. Cole, PV; Feyerabend, C; Russell, MA; Saloojee, Y; Sutton, SR, 1977)	1.89
"Nicotine plasma levels in dogs were examined by radioimmunoassay after intravenous administration of S-nicotine at the dosage of 100 microgram/kg."	( Plasma nicotine pharmacokinetics in dogs after intravenous administration: determination by radioimmunoassay. Castro, A; Monji, N, 1979)	2.16
"0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol."	( Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol. Barr, JE; Ryan, LJ; Sanders, B; Sharpless, SK, 1979)	0.5
" Dose-response curves for these pharmacological actions have been established."	( The central actions of nicotine on blood pressure and heart rate after administration via the left vertebral artery of anaesthetized cats. Distribution of nicotine into the brain after central application. Porsius, AJ; Van Zwieten, PA, 1978)	0.57
" Mecamylamine shifted the dose-response curves for nicotine to the right with a gradual depression."	( Comparative studies on anti-nicotinic action of hexamethonium, mecamylamine and adenosine in the guinea pig isolated ileum. Hayashi, E; Mori, M; Yamada, S, 1977)	0.51
" After extensive mathematical treatment of the data, the following results were established: (a) Equations for the dose-response surface of CO and nicotine were computed."	( Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats. Riedwyl, H; Stauffer, HP, 1977)	0.72
" blood pressure and saliva flow rate, upon sc dosing may be explained by the difference in plasma level peaks between sc and iv administration."	( Animal model and pharmacokinetic interpretation of nicotine poisoning in man. Brady, ME; Cacini, W; Patterson, AJ; Ritschel, WA; Saelinger, DA, 1979)	0.51
" Gallamine caused parallel rightward shifts of the dose-response curves to the agonists, with no depression of the maximal response."	( The inhibitory effect of gallamine on muscarinic receptors. Clark, AL; Mitchelson, F, 1976)	0.26
" Such values can be extimated by dose-response analysis of several epidemiological studies and by extrapolation of blood concentrations at different rates of intake for certain smoke components, such as carbon monoxide."	( Low-risk cigarettes: a prescription. Gori, GB, 1976)	0.26
" All these compounds led to abnormalities of the cervical vertebrae; at higher dosage interference with normal morphogenesis involved the whole vertebral column."	( Cholinomimetic teratogens: studies with chicken embryos. Landauer, W, 1975)	0.25
" In dose-response studies on the aortic strip, trans-metanicotine was significantly less active than nicotine."	( Nicotine-like actions of cis-metanicotine and trans-metanicotine. Bowman, ER; Chang, RS; McKennis, H; Wilson, KL, 1976)	1.94
" The individual models were tested through simulations of published studies of nicotine and cotinine infusions in man using similar dosing protocols to those reported."	( A physiologically based pharmacokinetic model for nicotine and cotinine in man. Balter, NJ; Robinson, DE; Schwartz, SL, 1992)	0.76
" Within regions intermediate between the dorsal posterior, mesencephalic tegmentum and posterior medulla, (-)-nicotine produced biphasic dose-response and time action curves."	( Opioid and nicotinic analgesic and hyperalgesic loci in the rat brain stem. Hamann, SR; Martin, WR, 1992)	0.5
" The AVP antagonist in the reduced dosage given alone had no effect on hormone levels."	( The role of vasopressin in the nicotine-induced stimulation of ACTH and cortisol in men. Bähr, V; Hader, O; Hensen, J; Oelkers, W; Scherer, G; Stalke, J, )	0.42
" Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals."	( Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats. Britos, SA; Keller, EA; Orsingher, OA, 1992)	0.7
" Dose-response curves to acetylcholine (ACh) and nicotine were established for pairs of tissues with and without epithelium, each pair receiving only one dose of nicotine."	( Nicotine-induced airway smooth muscle contraction: neural mechanisms involving the airway epithelium. Functional and histologic studies in vitro. Bleicher, S; Hahn, HL; Lang, M; Rausch, C; Zwerenz, S, )	1.83
" For each of these tests, animals that received chronic nicotine treatment were significantly less sensitive to nicotine challenge than were animals that received chronic saline treatment, as indicated by shifts to the right of dose-response curves."	( Tolerance to nicotine following chronic treatment by injections: a potential role for corticosterone. Collins, AC; Grun, EU; Pauly, JR, 1992)	0.9
" Together, these studies support the existence of a dose-response relationship for nicotine-induced euphoric sensations; suggest that they are more pronounced following overnight abstinence than following minimal deprivation, and in more dependent smokers; and characterize in detail the temporal features of these sensations."	( Euphoriant effects of nicotine in smokers. Pomerleau, CS; Pomerleau, OF, 1992)	0.82
" Physiological and biochemical responses showed significant dose-response relationships."	( Controlled dosing of nicotine via an Intranasal Nicotine Aerosol Delivery Device (INADD). Flessland, KA; Hariharan, M; Pomerleau, CS; Pomerleau, OF, 1992)	0.6
" Results for Experiment 2 showed very little effect of acute nicotine dosing on the overall responding and varying effects on the responding during the interval following unavoidable point losses."	( Human avoidance responding with added point loss: effects of tobacco and abstinence. Bennett, RH; Cherek, DR, 1992)	0.52
" While tonic blood pressure did not differ between the groups, the ability to modulate blood pressure (under feedback conditions) was restricted in smokers as compared to nonsmoking subjects; increasing nicotine dosage was accompanied by poorer performance."	( Effects of inhaled nicotine on instrumental learning of blood pressure responses. Birbaumer, N; Elbert, T; Grossmann, P; Krämer, J; Lutzenberger, W; Rockstroh, B, 1992)	0.8
" Pre-post drug difference scores for letter cancellation response time demonstrated a significant monotonic dose-response function, with significantly faster performance following cigarette than placebo."	( Cigarette smoking and nicotine gum (0, 2 and 4 mg): effects upon four visual attention tasks. Craig, D; Parrott, AC, 1992)	0.6
" Mice were dosed three times per day on gestational days 6-15."	( Alcohol and smokeless tobacco effects on the CD-1 mouse fetus. Dean, J; Fernandez, M; Mullet, D; Paulson, JO; Paulson, RB; Shanfeld, J, )	0.13
" The pattern of metabolites after iv dosing suggests that there is systemic reduction of NNO, although the magnitude of that reduction is small, with less than 3% reduced to nicotine."	( Disposition kinetics and metabolism of nicotine-1'-N-oxide in rabbits. Benowitz, NL; Duan, MJ; Jacob, P; Savanapridi, C; Yu, L, )	0.59
"Rats dosed orally with isosorbide dinitrate (1 mg kg-1) were exposed to smoke from standard and nicotine-reduced cigarettes for 8 min using a smoking machine."	( Influence of standard and nicotine-reduced cigarette smoke on plasma concentrations of isosorbide dinitrate and its metabolites in rats. Araki, Y; Furuno, K; Gomita, Y, 1991)	0.8
" Dose-response curves following noradrenergic stimulation were shifted to the right after 13 (but not after 180) days recovery."	( Vascular calcium overload produced by administration of vitamin D3 and nicotine in rats. Changes in tissue calcium levels, blood pressure, and pressor responses to electrical stimulation or norepinephrine in vivo. Atkinson, J; Capdeville, C; Chillon, JM; Henrion, D; Hicks, PE; Martin, JA; Oster, L; Thorin, E; Thorin-Trescases, N, 1990)	0.51
"01 microgram/kg) which had no effect on retention shifted the dose-response curve of LVP to the right."	( The enhancement of retention induced by vasopressin in mice may be mediated by an activation of central nicotinic cholinergic mechanisms. Baratti, CM; de Erausquin, GA; Faiman, CP, 1991)	0.28
" Lower concentrations of berberine (less than or equal to 5 x 10(-5) M) induced a parallel rightward shift of the dose-response curve of acetylcholine, suggesting that berberine is antagonizing the actions of acetylcholine at the receptors competitively."	( Pharmacological effects of berberine on the longitudinal muscle of the guinea-pig isolated ileum. Ochillo, RF; Tsai, CS, )	0.13
" Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks."	( Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction. Benowitz, NL, 1991)	0.6
" However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions."	( An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment. Collins, AC; Gross, SD; Marks, MJ; Pauly, JR, 1991)	0.51
" The results showed that the nicotine concentration in the patch, special relapse prevention methods, and the type of dosage (individual versus fixed dose) had no influence on therapeutic success."	( Smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy. Block, M; Buchkremer, G; Minneker, E, 1991)	0.83
" Some mouse strains, such as the C57BL/6, developed tolerance to nicotine, as measured by shifts to the right of dose-response curves, at the lowest infusion doses, whereas other strains, such as the C3H/2 and BUB, did not develop measurable tolerance until the highest infusion doses were used."	( Genotype influences the development of tolerance to nicotine in the mouse. Campbell, SM; Collins, AC; Marks, MJ; Romm, E, 1991)	0.77
"5 percent of users appeared to use the gum continuously at a daily dosage around the level needed to replace the nicotine addiction among most smokers, and for longer than the recommended three months."	( Patterns of nicotine gum use in a health maintenance organization. Hollis, JF; Johnson, RE; Stevens, VJ; Woodson, GT, )	0.72
" Injection into the fourth ventricle of ICI 174864 (100-300nmol) or DAMGO (100-300pmol) had no effects on the dose-response relationships for phenylbiguanide or nicotine."	( Chemosensitive cardiopulmonary afferents and the haemodynamic response to simulated haemorrhage in conscious rabbits. Evans, RG; Ludbrook, J, 1991)	0.48
" cis-3'-Hydroxycotinine was detected as an S(-)-nicotine metabolite in the urine of smokers as well as in the urine of rats and hamsters dosed with nicotine."	( Identification of cis-3'-hydroxycotinine as a urinary nicotine metabolite. Rustemeier, K; Schepers, G; Voncken, P, 1990)	0.78
" The VST method is especially useful to quantify drug plasma levels in pharmacokinetic evaluation of sustained-release dosage forms, where the precise quantification of low levels of drug is critical."	( Application of a variance-stabilizing transformation approach to linear regression of calibration lines. Banfield, C; Bialer, M; Gonzalez, MA; McLean, AM; Ruggirello, DA, 1990)	0.28
"In the first experiment a conditioned taste aversion paradigm was used to characterize a dose-response curve for the aversive properties of nicotine in male Sprague-Dawley rats."	( Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration. Gilbert, DG; Jensen, RA; Landrum, TA; Meliska, CJ; Szary, AB, 1990)	0.74
" Eight subjects received a 14-hr infusion of deuterium-labeled nicotine dosed to achieve levels of nicotine similar to those while smoking cigarettes for each individual (average, 33."	( Intravenous nicotine replacement suppresses nicotine intake from cigarette smoking. Benowitz, NL; Jacob, P, 1990)	0.9
" A dose-response relationship was observed between number of cigarettes smoked per day at baseline and weight gain."	( Weight change among participants in a large sample minimal contact smoking relapse prevention trial. Fortmann, SP; Killen, JD; Newman, B, 1990)	0.28
" Convex dose-response relationships were found between the amount smoked and ABP hemoglobin adduct levels or urinary mutagenicity."	( Carcinogen hemoglobin adducts, urinary mutagenicity, and metabolic phenotype in active and passive cigarette smokers. Bartsch, H; Caporaso, N; Coda, M; Kadlubar, F; Malaveille, C; Skipper, P; Talaska, G; Tannenbaum, SR; Vineis, P, 1990)	0.28
" Our results suggest the dose-response curves differ for nicotine gum's reinforcing, withdrawal-suppression and self-reported effects."	( Effect of dose on nicotine's reinforcing, withdrawal-suppression and self-reported effects. Fenwick, JW; Gust, SW; Hughes, JR; Keenan, RM, 1990)	0.86
" The alteration of nicotine's dose-response curves for depression of spontaneous activity and antinociception was determined in the presence of increasing concentrations of pempidine."	( Pharmacological evaluation of the antagonism of nicotine's central effects by mecamylamine and pempidine. Martin, BR; Martin, TJ; May, EL; Suchocki, J, 1990)	0.86
" Reliable dose-response studies in smokers and nonsmokers are needed, and use of the SC route for this purpose is discussed."	( Non-smokers show acute tolerance to subcutaneous nicotine. Feyerabend, C; Jarvis, MJ; Jones, G; Russell, MA, 1990)	0.53
" At a concentration of (+)-nicardipine (10(-7) M) which inhibits most of the release stimulated by 50 mM potassium, the response to 3 X 10(-5) M nicotine remains; however, the dose-response curve to nicotine is shifted slightly to the left."	( Stimulus secretion coupling in cultured chromaffin cells. Dependency on external sodium and on dihydropyridine-sensitive calcium channels. Adams, M; Boarder, MR; Marriott, D, 1987)	0.47
" From the dose-response curve, 50% inhibition of nicotine-evoked striatal dopamine release occurred at 5 microM perhydrohistrionicotoxin, a value similar to that obtained in frog sartorius muscle and Electrophorus electroplax."	( The neurotoxin histrionicotoxin interacts with the putative ion channel of the nicotinic acetylcholine receptors in the central nervous system. Albuquerque, EX; Lunt, GG; Rapier, C; Wonnacott, S, 1987)	0.53
" Although intercigarette yield comparisons revealed no significant EEG differences between yields, comparison of the effects of smoking each yield with sham smoking indicated the presence of a qualitative dose-response effect whereby increasing T/N yields resulted in a progressive posterior-to-anterior spreading of significant relative power changes within both theta and alpha frequency bands."	( Brain electrical imaging the dose-response effects of cigarette smoking. Knott, VJ, 1989)	0.28
" Carbachol-induced PKC translocation was concentration-dependent, with a biphasic dose-response curve yielding approximate EC50 values of 10(-6) M and 10(-4) M for the high- and low-affinity components, respectively."	( Nicotinic and muscarinic agonists stimulate rapid protein kinase C translocation in PC12 cells. Kiyasu, E; Messing, RO; Sneade, AB; Stevens, AM, 1989)	0.28
" 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)	0.84
" Substitution tests with other doses and drugs showed that, after the fading procedure, dose-response curves were shifted to lower doses for PTZ, Ro 5-3663, and nicotine Similarly, the dose of diazepam required to block the low dose of PTZ was lower than that required to block the higher dose of PTZ."	( Sensitivity of pentylenetetrazol discrimination increased by a stimulus fading technique. Emmett-Oglesby, MW; Harris, CM; Lal, H, 1989)	0.47
" Dose-response curves were constructed for each strain on each test in a multitest battery."	( Genetic influences on nicotine responses. Collins, AC; Marks, MJ; Stitzel, JA, 1989)	0.59
"Tolerance to nicotine's disruptive effects on operant responding develops rapidly over a 14-36 day repeated dosing period in both rats and mice."	( Nicotine-induced tolerance and dependence in rats and mice: studies involving schedule-controlled behavior. Hendry, JS; Meltzer, LT; Rosecrans, JA; Stimler, CA, 1989)	2.09
" Hexamethonium impaired the dose-response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol."	( Carbachol injection into the medial preoptic area induces natriuresis, kaliuresis and antidiuresis in rats. Camargo, LA; De Luca Júnior, LA; Menani, JV; Renzi, A; Saad, WA, 1989)	0.28
" The mean maternal plasma nicotine level for the low dosage (1 X) group was 99."	( Effect of smokeless tobacco on the development of the CD-1 mouse fetus. Paulson, J; Paulson, R; Price, T; Sachs, L; Shanfeld, J, 1989)	0.58
" Non-smokers absorb measurable amounts of nicotine from breathing other people's smoke, and dose-response relationships are apparent."	( Application of biochemical intake markers to passive smoking measurement and risk estimation. Jarvis, MJ, 1989)	0.54
" These results suggest that standardized dosage is preferred to individually adapted dosage."	( The effect of different dosages of a transdermal nicotine substitution system on the success rate of smoking cessation therapy. Block, M; Buchkremer, G; Minneker, E, 1989)	0.53
" Dose-response curves for angiotensin II and bradykinin were shown to be double-sigmoidal, with the first EC50 in the nM range; much lower than that for acetylcholine, nicotine or histamine."	( Neuropeptides and other secretagogues in bovine chromaffin cells: their effect on opioid peptide metabolism. Bommer, M; Herz, A, )	0.33
" Dose-response curves for sensitivity to IP nicotine-induced seizures were constructed for the 19 inbred strains and a heterogeneous stock (HS/Ibg) of mice."	( Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. Collins, AC; Miner, LL, 1989)	0.86
" After drug combinations had been tested, the nicotine dose-response curve was unchanged from its previous values, and naltrexone alone produced no tendency to decrease response rate."	( Evidence for opioid mechanisms in the behavioral effects of nicotine. Coen, KM; Corrigall, WA; Herling, S, 1988)	0.78
" Using a statistical method developed for the CPP paradigm, dose-response curves were obtained for the rewarding and aversive effects of nicotine as measured by its ability to alter previously determined baseline preferences obtained from the control animals."	( Pharmacologic characterization of nicotine-induced conditioned place preference. Fudala, PJ; Iwamoto, ET; Teoh, KW, 1985)	0.75
" R-(+)-N-methylnicotinium salt was isolated from the urine of guinea pigs that had been chronically dosed ip with R-(+)-nicotine."	( Stereospecific in vivo N-methylation of nicotine in the guinea pig. Crooks, PA; Cundy, KC; Sato, M, )	0.61
"N-Methylnornicotinium ion has been identified as a metabolite in the urine of male Hartley guinea pigs that had been chronically dosed ip with R-(+)-nicotine."	( N-Methylnornicotinium ion, a new in vivo metabolite of R-(+)-nicotine. Crooks, PA; Sato, M, )	0.57
"The results of a dose-response study of the effects of nicotine on exploratory behavior in male rats is reported."	( Effects of nicotine on exploratory behavior in rats: correlation with regional brain monoamine levels. Lee, EH, 1985)	0.91
"The dose-response curves of the central and peripheral airways to intravenously injected nicotine were studied in 55 anesthetized dogs."	( Dose-response curves of central and peripheral airways to nicotine injections in dogs. Haga, T; Miyano, M; Nakamura, M; Sasaki, H; Takishima, T, 1986)	0.74
" To determine the time after administration of nicotine and dosage for neurochemical studies, locomotor activity of CD-1 mice was determined at 5 min intervals between 0-60 min."	( Locomotor activity as a predictor of times and dosages for studies of nicotine's neurochemical actions. Freeman, GB; Gibson, GE; Sherman, KA, 1987)	0.76
"0 ng/ml for the Dosage I group of dams, and in the range of 34."	( Effect of smokeless tobacco on the development of the CD-1 mouse fetus. Ismail, M; Paulson, J; Paulson, R; Sachs, L; Shanfeld, J, 1988)	0.27
" Each of these three modalities--weight control, alcohol restriction, and sodium restriction--was found to be capable not only of independently controlling blood pressure (particularly in patients with mild hypertension) but also of reducing the number and dosage of prescribed pharmacological agents, should their prescription be indicated."	( Nonpharmacological approaches to the control of high blood pressure. Final report of the Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. , 1986)	0.27
" The dose-response curve for nicotine was bell shaped, with a threshold at 10(-7) M, a maximum at 10(-5) M, and diminished release at higher concentrations, an observation indicative of desensitization."	( Direct and continuous detection of ATP secretion from primary monolayer cultures of bovine adrenal chromaffin cells. Bourke, JE; Livett, BG; White, TD, 1987)	0.56
" In different groups of rats trained to discriminate nicotine or midazolam separately from saline, neither drug appreciably altered the dose-response curve for the other, suggesting a minimal role for pharmacological interactions when effects of mixtures were assessed."	( Discriminative stimulus effects of a nicotine-midazolam mixture in rats. Norris, EA; Rauch, RJ; Stolerman, IP, 1987)	0.8
" Dose-response curves were constructed for each measure."	( Genetic influences on acute responses to nicotine and nicotine tolerance in the mouse. Collins, AC; Marks, MJ; Miner, LL, 1988)	0.54
" Strain differences were observed for the dose-response to the second injection; however, no effect of acute nicotine pretreatment was demonstrated."	( Influence of genotype on nicotine-induced increases of plasma corticosterone in mice as a result of acute nicotine pretreatment. Martin, BJ; Wehner, JM, 1988)	0.79
" Finally, the confirmation that dose-response relationships exist between cotinine concentrations and self-reported passive smoking validates questionnaire measures of the degree of environmental smoke exposure."	( Uptake of environmental tobacco smoke. Jarvis, MJ, 1987)	0.27
" A dose-response relationship was observed for cigarette exposures."	( Cigarette and nicotine chewing gum toxicity in children. Kulig, K; Rumack, BH; Smolinske, SC; Spiller, SK; Spoerke, DG; Wruk, KM, 1988)	0.64
" In the presence of atropine (10(-5) M), the dose-response curve for ACh was shifted to the right."	( Voltage-independent catecholamine release mediated by the activation of muscarinic receptors in guinea-pig adrenal glands. Nakazato, Y; Ohga, A; Oleshansky, M; Tomita, U; Yamada, Y, 1988)	0.27
" Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0."	( Atrioventricular responses of canine heart following chronic unilateral vagotomy. Anagnostelis, C; Blomquist, TM; Priola, DV; Sanchez-Wilson, C, 1987)	0.27
" However, when animals were tested in a fixed-ratio:15 (FR:15) paradigm, nicotine produced a steep, biphasic dose-response curve."	( Task-specific effects of nicotine in rats. Intracranial self-stimulation and locomotor activity. Michael, RP; Schaefer, GJ, 1986)	0.81
" Monitoring of smoke intakes could supplement epidemiological approaches and provide earlier evidence of whether changing cigarette designs lead to any significant dosage reduction that could affect the risk of disease."	( Reduction of tar, nicotine and carbon monoxide intake in low tar smokers. Feyerabend, C; Jarvis, MJ; Russell, MA; Saloojee, Y, 1986)	0.6
" The final experiment found that repeated dosing with one 2 mg NNS on an hourly schedule for six hours produced a reliable increase in tapping speed after each dose with no evidence of acute tolerance."	( Effects of nicotine on finger tapping rate in non-smokers. Jarvis, MJ; West, RJ, 1986)	0.66
" A dose-response curve was obtained for the place conditioning effect of nicotine as measured by its ability to alter baseline preferences calculated from control rats."	( Further studies on nicotine-induced conditioned place preference in the rat. Fudala, PJ; Iwamoto, ET, 1986)	0.83
" A dose-response relationship of gum use to outcome was identified."	( Smoking cessation in family practice: the effects of advice and nicotine chewing gum prescription. Best, JA; Page, AR; Schlegel, RP; Walters, DJ, 1986)	0.51
" Plasma concentration monitoring may be necessary for optimal dosing of theophylline in such patients."	( Cigarette abstinence, nicotine gum, and theophylline disposition. Benowitz, NL; Jacob, P; Lee, BL, 1987)	0.59
" Compared to the control (untreated) group of animals, the 24-hour hydroxyproline output (relative to creatinine) was lower for all dilutions of smoke and showed a negative dose-response relationship."	( Preliminary studies of urinary hydroxyproline levels in rodents and in smokers. Read, GA; Thornton, RE, 1985)	0.27
" The slope of the dose-response curve was quite shallow (6-8% change in binding per doubling dose), resulting in between-assay CVs of 15 to 20%."	( Improved 125I radioimmunoassay for cotinine by selective removal of bridge antibodies. Haddow, JE; Holman, MS; Knight, GJ; Wylie, P, 1985)	0.27
" Neither (+)- nor (-)-BN altered blood pressure and heart rate in rats in this dosage range."	( Pharmacological effects of 1,2,3,5,6,10b-hexahydropyrido[2,3g]indolizine, a bridged-nicotine analog. Aceto, MD; Awaya, H; Egle, JL; Kachur, JF; Martin, BR; May, EL, 1986)	0.5
" dose of nicotine activated both lung and trachea ODC in a dose-response fashion."	( Effect of nicotine and N'-nitrosonornicotine on rat lung and trachea ornithine decarboxylase activity. Crooks, PA; Olson, JW, 1985)	1.09
" Both in vivo and in vitro methods demonstrated a leftward shift of the dose-response curve for nicotine in denervated hearts, indicative of denervation hypersensitivity."	( Comparison of in vivo and in vitro cholinergic responses of normal and denervated canine hearts. Anagnostelis, C; Priola, DV; Smith, DC, 1985)	0.49
" The results pointed out that nicotine dosage and constitutional make-up may interact in determining the physiological effects produced."	( Individual nicotine requirements: the relationship between differences in nicotine intake and physiological response. Karanci, NA, 1985)	0.95
"To establish dose-response relationships for nicotine (acute and subacute administration), we measured hemodynamic parameters as well as circulating and tissue catecholamines in sympathetically innervated organs in rats."	( Changes in peripheral and central catecholaminergic and serotoninergic neurons of rats after acute and subacute administration of nicotine. Dominiak, P; Grobecker, H; Kees, F, 1984)	0.73
" Two studies on a total of 80 rats found an inverse dose-response relationship between nicotine administration and body weight without changes in bland food or water consumption."	( Effects of nicotine on body weight and food consumption in rats. Bowen, DJ; Grunberg, NE; Morse, DE, 1984)	0.88
" When simple dosage rules are followed people who chew nicotine gum for a few months to stop smoking lower their exposure to nicotine."	( Chewing nicotine gum for 3 months: what happens to plasma nicotine levels? McNabb, ME, 1984)	0.95
" In mice, maternal exposures to a small dosage of nicotine throughout both gestational and lactating periods appear to induce more baby lung changes than when the exposure to nicotine is limited to either period alone."	( The cumulative scanning electron microscopic changes in baby mouse lungs following prenatal and postnatal exposures to nicotine. Chen, MF; Schraufnagel, DE; Wang, NS; Yao, YT, 1984)	0.73
" Dose-response curves for nicotine-induced seizures were constructed for both parental strains and all crosses derived from them."	( Classical genetic analysis of nicotine-induced seizures and nicotinic receptors. Collins, AC; Marks, MJ; Miner, LL, 1984)	0.86
" A dose-response study similar to the first was then carried out, and little or no tolerance was found to the hypodipsic action of nicotine."	( Some effects of nicotine on food and water intake in undeprived rats. Clarke, PB; Kumar, R, 1984)	0.82
"), a nicotinic antagonist with both central and peripheral effects, shifted the nicotine dose-response curve to the right by about 1 log unit and blocked nicotine-induced emesis."	( Maintenance of behavior by postponement of scheduled injections of nicotine in squirrel monkeys. Spealman, RD, 1983)	0.73
" 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)	0.48
" Active compounds exhibited an inverted U-shaped dose-response curve."	( Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam. Butler, DE; L'Italien, YJ; Marriott, JG; Nordin, IC; Poschel, PH; Zweisler, L, 1984)	0.27
" These results indicate that nicotine continuously infused into the isolated rat heart depresses heart rate and coronary flow in a dose-response manner and that these changes are reversible over the range of concentrations used."	( Nicotine-depressed function in isolated rat heart. McGrath, JJ; Smith, D, 1984)	2
" Dosing protocols for the extract and for nicotine were designed to achieve blood levels of nicotine approximating those attained by consumption of 2 packs/day of University of Kentucky 2Rl reference cigarettes."	( Chronic administration of water soluble tobacco smoke extract or nicotine fails to influence porcine coronary artery reactivity. Diamond, L; Gillespie, MN; Saxon, DJ, 1984)	0.77
" Dose-response relationships for optically pure (-)- and (+)nicotine as well as antagonistic effects were examined in both groups of rats."	( Discriminative stimulus properties of the optical isomers of nicotine. Aceto, MD; Harris, LS; Meltzer, LT; Rosecrans, JA, 1980)	0.74
" A general excitatory effect of nicotine was observed in the photocell chamber, with the high dosage greatly increasing activity for younger and female animals."	( Effects of nicotine on two types of motor activity in rats. Abrams, OR; Bergondy, M; Biner, PM; Bryson, R; McNair, E, 1981)	0.94
" As a conclusion, it is suggested that altered sensitivity of brain tissue rather than changes in bioavailability must explain variations in dose-response relationship which are frequently believed to be seen when fentanyl is used in patients with chronic drug administration."	( [Biotransformation of fentanyl. III. Effect of chronic drug exposure on the distribution, metabolism and excretion in the rat]. Brandt, K; Daub, D; Hunger, L; Lehmann, KA, 1983)	0.27
" Dose-response curves for VIP and enkephalin release by the above secretagogues were similar but not identical."	( Primary cultures of bovine chromaffin cells synthesize and secrete vasoactive intestinal polypeptide (VIP). Eiden, LE; Eskay, RL; Hotchkiss, AJ; Pollard, H; Scott, J, 1983)	0.27
" The nicotine dosage and flash intensity factors both had significant effects on peak-to-peak amplitudes while only the flash intensity factor affected peak latencies."	( Effects of nicotine on the visual evoked response. Baettig, K; Etkin, MW; Harry, GJ; Kallman, MJ; Kallman, WM; Rosecrans, JA; Woodson, PP, 1982)	1.17
" All active compounds gave inverted U-shaped dose-response curves."	( Cognition-activating properties of 3-(Aryloxy)pyridines. Butler, DE; Marriott, JG; Poschel, BP, 1981)	0.26
" Systematic dose-response functions have also been found under these conditions."	( Reinforcing and other behavioral effects of nicotine. Dougherty, J; Kostenbauder, HB; Miller, D; Todd, G, 1981)	0.52
"The effect of oral nicotine dosage on the morphology of the rat gastric mucosa was studied."	( Effect of nicotine on the morphology of the rat gastric mucosa. Jarvis, LR; Whitehead, R, 1980)	0.99
"Nicotine was given intravenously to subjects during acid and alkaline urine conditions in doses and a dosing schedule to simulate cigarette smoking."	( Disposition kinetics and effects of intravenous nicotine. Benowitz, NL; Jacob, P; Rosenberg, J; Wilson, KM, 1980)	1.96
" From dose-response curves, we find that the ED50 for both cytisine and dimethylphenylpiperazinium (DMPP) is 20 microM and for ACh is 52 microM."	( Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic ACh receptor subunits. Cooper, E; De Koninck, P; Mandelzys, A, 1995)	0.29
" However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect."	( Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant. Andersson, M; Lunell, E; Molander, L, 1995)	0.95
"Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction (2 weeks of 22 mg followed by 2 weeks of 11 mg)."	( Varying nicotine patch dose and type of smoking cessation counseling. Baker, TB; Croghan, IT; Fiore, MC; Hays, JT; Hurt, RD; Jorenby, DE; Lewis, SF; Offord, KP; Smith, SS, 1995)	0.99
" At week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d."	( High-dose nicotine patch therapy. Percentage of replacement and smoking cessation. Croghan, IT; Dale, LC; Hurt, RD; Lawson, GM; Offord, KP; Schroeder, DR, 1995)	0.69
" A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief."	( High-dose nicotine patch therapy. Percentage of replacement and smoking cessation. Croghan, IT; Dale, LC; Hurt, RD; Lawson, GM; Offord, KP; Schroeder, DR, 1995)	0.69
"The dose-response and time-course effects of acute nicotine on total biopterin concentrations in the striatum, hypothalamus and hippocampus were examined in rats by using high performance liquid chromatography (HPLC) with fluorescence detection."	( Nicotine enhances brain biopterin concentration in rats. Lee, EH; Tsai, MJ, 1995)	1.99
" Nicotine enhanced release, with a bell-shaped dose-response curve."	( Lesion with the neurotoxin AF64A alters hippocampal cholinergic receptor function. Potter, PE; Thorne, B, 1995)	1.2
" Oral dosing of Nicotinell and Niconil (two patches per dog) produced vomiting in 2 of 12 exposures."	( Absorption and adverse effects following topical and oral administration of three transdermal nicotine products to dogs. Gorsline, J; Matsushima, D; Prevo, ME, 1995)	0.86
" The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice."	( Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice. Daly, JW; Jacobson, KA; Nikodijević, O; Shi, D, )	0.13
" In the first experiment, this drug produced a biphasic dose-response curve with improved performance at the 20-mg/kg dose but not at 10 or 40 mg/kg."	( Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze. Abood, L; Levin, ED; Rose, JE, )	0.13
"8 times that of the non-smokers, suggesting that the dose-response relationship between smoking and lung cancer is no less step in women than in men."	( Urinary nicotine metabolite excretion and lung cancer risk in a female cohort. de Waard, F; Ellard, GA; Kemmeren, JM, 1995)	0.73
") were found to enhance nicotine-induced antinociception by shifting its dose-response curve to the left."	( Involvement of calcium and L-type channels in nicotine-induced antinociception. Damaj, MI; Martin, BR; Welch, SP, 1993)	0.85
" However, we cannot exclude the possibility that intermittent bolus-like dosing of nicotine from cigarettes could have different effects from those produced by continually released transdermal nicotine."	( Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. Benowitz, NL; Fitzgerald, GA; Wilson, M; Zhang, Q, 1993)	1.95
" Based upon dose-response and time-course studies with nicotine in normal animals, the neuroendocrine responses to nicotine (0."	( Exposure to threshold doses of nicotine in utero: II. Neuroendocrine response to nicotine in adult male offspring. Acosta, S; Afrane S [corrected to Acosta, S]; Au, D; Hsieh, C; Lutchmansingh, P; Lydecker, S; McCracken, JT; Poland, RE, 1994)	0.82
" Although mostly nonsignificant, all of the reported asthma-like symptoms were related especially to maternal smoking, with a trend of a dose-response relationship."	( Adverse effects of the indoor environment on respiratory health in primary school children. Cuijpers, CE; Sturmans, F; Swaen, GM; Wesseling, G; Wouters, EF, 1995)	0.29
" All studies used a nasal spray method of nicotine dosing or controlled smoking (paced puffing) to control acute nicotine exposure, an essential methodological feature of any research on individual differences in acute responses to nicotine."	( Individual variability in responses to nicotine. Perkins, KA, 1995)	0.82
" They also monitor each patient for the dose-response effect, adverse drug reactions, drug interactions, concurrent medical conditions, and progress and outcome."	( Pharmacists' role in a smoking-cessation program at a managed health care organization. Gauen, SE; Lee, NL, 1995)	0.29
"The nicotine gum is a flexible dosing form that allows for self-titration of nicotine."	( Nicotine chewing gum and nicotine patch. Fagerström, KO; Tönnesen, P, 1995)	2.29
" Recently we found that spinal intrathecal administration of nicotine dose-dependently inhibits bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat and that the dose-response curve for the inhibition of BK-induced PE by intrathecal nicotine is shifted to the left, by six orders of magnitude, after surgical interventions in the abdominal cavity, which might have interrupted visceral afferents to the neuraxis."	( Role of vagal afferents and spinal pathways modulating inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine. Basbaum, AI; Benowitz, NL; Dallman, MF; Heller, PH; Jänig, W; Levine, JD; Miao, FJ, 1994)	0.74
" Nicotine transdermal systems ("patches") delivering a total of 0, 22 or 44 mg per 24 h were applied daily at a constant dose during each 7-day condition; the order of dosing conditions was varied according to a randomized, double-blind, crossover design."	( Transdermal nicotine: reduction of smoking with minimal abuse liability. Bunker, EB; Henningfield, JE; Pickworth, WB, 1994)	1.58
" Improvement was associated with active nicotine dosing and involved diminished tremor and disorganized thinking in one patient and diminished bradykinesia and increased energy in the other."	( Nicotine may relieve symptoms of Parkinson's disease. Fagerström, KO; Giordani, B; Pomerleau, O; Stelson, F, 1994)	2
" gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks."	( Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Feyerabend, C; Gustavsson, G; Russell, MA; Sawe, U; Stapleton, JA; Wiseman, D; Wiseman, SM, 1995)	0.52
"Nicotine-replacement therapy (NRT) by gum, transdermal patch, intranasal spray, or inhalation is expensive but how effective is it? We have done a meta-analysis of controlled trials to see how effects on abstinence rates are influenced by the clinical setting, the level of nicotine dependency, the dosage of NRT, and the intensity of additional advice and support offered."	( Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Fowler, G; Lodge, M; Mant, D; Silagy, C, 1994)	2.02
" In 28 animals, an initial dose-response curve for glutamate (37, 74, and 148 pmol/60 nL) was obtained."	( Inhibition by ethanol of the cardiovascular effects of glutamate in the nucleus of the solitary tract. Appalsamy, M; Mosqueda-Garcia, R; Robertson, D, 1994)	0.29
" For this purpose, complete nicotine dose-response curves were made for mean arterial pressure and heart rate."	( Cardiovascular effects of different schedules of nicotine administration on spinal rats: influence of pentobarbital. Cruz, SL; Fernández-Guasti, A; Villarreal, JE, 1994)	0.84
"5 mg/kg/day dosage from gestational day (GD) 6 to term."	( Effects of prenatal nicotine exposure on the morphogenesis of somatosensory cortex. Roy, TS; Sabherwal, U, )	0.45
" In abstinent patients, effect of nicotine dosage was observed with greater weight gain in placebo than 21 mg TTS patients and greater decrease in heart rate in placebo than 21 mg TTS patients."	( Cholesterol changes in smoking cessation using the transdermal nicotine system. Transdermal Nicotine Study Group. Allen, SS; Gorsline, J; Hatsukami, D, 1994)	0.81
" Each day, subjects also received a challenge dose of 20 micrograms/kg 30 min after the previous dosing to assess acute tolerance."	( Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans. Caggiula, AR; Fonte, C; Goettler, J; Grobe, JE; Jacob, RG; Perkins, KA; Reynolds, WA; Scierka, A; Stiller, RL, 1994)	0.51
" nicotine dose-response curve was seen in normal rats after blocking peripheral nicotinic receptors by hexamethonium or after bilateral denervation of the adrenal medulla."	( Adrenal medullary modulation of the inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine. Basbaum, AI; Benowitz, NL; Dallman, MF; Levine, JD; Miao, FJ, 1993)	1.41
" This increase of infarct size exhibited a dose-response relation."	( Exposure to environmental tobacco smoke increases myocardial infarct size in rats. Glantz, SA; Parmley, WW; Sievers, RE; Sun, YP; Wolfe, CL; Zhu, BQ, 1994)	0.29
"Human scalp hair retains the past dosage history over a rather long period of time, acting as 'tape-recorder'."	( Utilization of hair analysis for therapeutic drug monitoring with a special reference to ofloxacin and to nicotine. Uematsu, T, 1993)	0.5
" Plasma nicotine levels indicated comparable dosing between methods."	( Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray. Fonte, C; Grobe, JE; Perkins, KA; Reynolds, WA; Sexton, JE; Stiller, RL, 1994)	0.97
"Pooled abstinence rates and combined odds ratios (ORs) at end of treatment and 6-month follow-up were examined overall and in terms of patch type (16-hour vs 24-hour), patch treatment duration, dosage reduction (weaning), counseling format (individual vs group), and intensity of adjuvant behavioral counseling."	( The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. Baker, TB; Fiore, MC; Jorenby, DE; Smith, SS, )	0.43
" Therefore, altering the form of nicotine dosing may allow for selective therapeutic action in efforts to develop safer and less addictive nicotine replacement therapies."	( Nicotine delivery kinetics and abuse liability. Henningfield, JE; Keenan, RM, 1993)	2.01
" 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)	1.96
"To determine the effectiveness of nicotine replacement therapies (NRTs) (including gum, transdermal patch, intranasal spray, and inhaled preparations) in facilitating smoking cessation, and to determine whether the effect was influenced by the clinical setting in which the smoker was recruited and treated, the level of nicotine dependency, the dosage of NRT used, or the intensity of additional advice and support offered to the smoker."	( The effectiveness of nicotine replacement therapies in smoking cessation. Fowler, G; Lodge, M; Mant, D; Silagy, C, 1994)	0.89
" Adduct analyses with varying amounts of DNA from lungs of mid- and high-exposure animals clearly indicate that the dose-response for DNA adduct formation is nonlinear."	( Ninety-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette: DNA adducts and alveolar macrophage cytogenetics. Brown, BG; Coggins, CR; Doolittle, DJ; Hayes, AW; Lee, CK; Reed, EA, 1993)	0.29
" Cumulative dosing tests for the discriminative stimulus properties consisted of two to five trials of FR20 schedule; responses for both levers were reinforced."	( [Discriminative stimulus properties of ephedra herb (Ephedra sinica) in rats]. Furuya, I; Watanabe, S, 1993)	0.29
" Once criterion performance was attained, dose-response experiments indicated an ED50 value for P rats = 354."	( P and NP rats respond differently to the discriminative stimulus effects of nicotine. Gordon, TL; Meehan, SM; Schechter, MD, 1993)	0.52
" Smaller responses to the challenge dose as a function of increasing prior nicotine dosing during Trials 1-4 were viewed as evidence for acute tolerance."	( Chronic and acute tolerance to subjective effects of nicotine. Caggiula, A; Epstein, LH; Grobe, JE; Jacob, RG; Perkins, KA; Stiller, RL, 1993)	0.77
" Dose-response analyses of the release and efflux assays demonstrated that chronic nicotine infusion evoked decreases in the maximal effects of nicotine on the functional assays; potency was not altered by chronic drug treatment."	( Downregulation of nicotinic receptor function after chronic nicotine infusion. Collins, AC; Grady, SR; Marks, MJ, 1993)	0.75
" Animals also received four injections of nicotine to determine whether repetitive dosing leads to progressive reduction of the norepinephrine response."	( Detection by in vivo microdialysis of nicotine-induced norepinephrine secretion from the hypothalamic paraventricular nucleus of freely moving rats: dose-dependency and desensitization. Matta, SG; Sharp, BM, 1993)	0.82
" Findings from a second study also reflect the linear dose relationship for this Nicotine Transdermal System within the 7 to 21 mg/day dosage range."	( Steady-state pharmacokinetics and dose relationship of nicotine delivered from Nicoderm (Nicotine Transdermal System). Dye, D; Gorsline, J; Gupta, SK; Rolf, CN, 1993)	0.76
" In each experiment, order of dosing conditions was determined by a Latin square design."	( Effects of 5-hydroxytryptamine3 antagonist, ondansetron, on cigarette smoking, smoke exposure, and mood in humans. Apfelbaum, JL; Lichtor, JL; Zacny, JP; Zaragoza, JG, 1993)	0.29
"(a) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting; (b) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation."	( Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. Connor, P; Feyerabend, C; Gustavsson, G; Russell, MA; Sawe, U; Stapleton, JA; Wiseman, SM, 1993)	0.77
" Nicotine dose-response curves gave EC50 values of 24 and 830 microM for alpha 7 and alpha L1 respectively."	( A nicotinic acetylcholine receptor subunit from insect brain forms a non-desensitising homo-oligomeric nicotinic acetylcholine receptor when expressed in Xenopus oocytes. Amar, M; Lunt, GG; Thomas, P; Wonnacott, S, 1995)	1.2
" Whereas the mechanism for this nicotine effect is currently not known, future experiments will look at dose-response relationships, the role of nicotine receptors, and possible neuroprotective potential of nicotine in this KA-induced syndrome."	( Nicotine blocks kainic acid-induced wet dog shakes in rats. Borlongan, CV; Sanberg, PR; Shytle, RD, 1995)	2.02
" Mean (+/- SD) peak plasma level of the last dosing interval was 32."	( Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler. Andersson, SB; Kuylenstierna, F; Lunell, E; Molander, L, 1996)	0.55
" The effects of nicotine in people are influenced by the rate and route of dosing and by the development of tolerance."	( Pharmacology of nicotine: addiction and therapeutics. Benowitz, NL, 1996)	0.99
" However, a significant shift in (-)-epibatidine's dose-response curve was obtained in animals that received (-)-epibatidine."	( Tolerance to the antinociceptive effect of epibatidine after acute and chronic administration in mice. Damaj, MI; Martin, BR, 1996)	0.29
" Dose-response determinations then showed that the devaluation procedure had indeed attenuated the response to midazolam, whereas the previously overshadowed response to nicotine was restored."	( Reversal of overshadowing in a drug mixture discrimination in rats. Stolerman, IP; White, JA, 1996)	0.49
" To define better the optimal dosing of nicotine patch therapy, we undertook an open-label study to determine the safety and tolerability of 44 mg/day dose for smoking cessation in subjects smoking > or = 20 cigarettes per day."	( High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Croghan, IT; Fredrickson, PA; Gomez-Dahl, L; Hurt, RD; Lauger, G; Lee, GM; Offord, KP; Wingender, L, 1995)	0.87
"), caused a rightward displacement of the dose-response curves to both alpha- and beta CGRP; mean dose-ratios, 5 min after antagonist administration, were 14 and 24 respectively."	( NK1 and CGRP receptor-mediated dilatation of the carotid arterial bed of the anaesthetized rabbit. Beattie, DT; Connor, HE; Perren, MJ, 1996)	0.29
" When stimulated by nicotine or carbachol, the dose-response curves of both cell fractions yielded similar EC50s for the release of adrenaline and noradrenaline."	( Catecholamine release from fractionated chromaffin cells. Krause, W; Livett, BG; Lübke, C; Michael, N; Oehme, P, 1996)	0.62
" Dose-response extrapolation-supported by a more solid database for active smokers-reflects a possible increase in lung cancer that appears to be more than one order of magnitude lower than indicated by the epidemiological studies that have been used to support regulatory action in the United States."	( Environmental tobacco smoke and lung cancer: a reappraisal. Nilsson, R, 1996)	0.29
" Each nicotine/placebo dosing was followed by assessment of energy expenditure by indirect calorimetry."	( Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers. DiMarco, A; Perkins, KA; Sexton, JE, 1996)	1.07
" In the three types of preparations, the dose-response curves for acetylcholine were alike with similar EC50s."	( Spontaneous tone in different types of longitudinal muscle preparations of guinea pig ileum. Gomi, Y; Mambo, T; Shibayama, T; Suzuki, N, 1995)	0.29
" Neither the prolactin nor the ACTH response was augmented significantly in the animals exposed prenatally to either nicotine dosage regimen, although there was a strong trend for the augmentation to occur in the low-dose nicotine exposed animals."	( Exposure to threshold doses of nicotine in utero: III. Augmentation of the prolactin and ACTH response to 8-OH DPAT by desipramine treatment is compromised in adult male offspring. Acosta, S; Au, D; Lutchmansingh, P; McCracken, JT; McGeoy, S; Poland, RE; Que, M, 1996)	0.79
" A further aim was to compare the effect of ad libitum with fixed dosage of nasal nicotine spray."	( Recycling of hard-core smokers with nicotine nasal spray. Jørgensen, S; Mikkelsen, K; Nørregaard, J; Tønnesen, P, 1996)	0.79
" In conscious rats, the dose-response curves of muscarinic agonists arecoline and pilocarpine, cholinesterase inhibitors soman and physostigmine rather than GABA receptor antagonist pentylenetetrazol or glycine receptor antagonist strychnine for producing EEG seizures were shifted leftwards by acutely repeated injections of nicotine."	( Regulatory effects of acutely repeated nicotine treatment towards central muscarinic receptors. Cui, WY; Liu, CG; Wang, H, 1996)	0.74
" The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers."	( Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Conners, CK; Erhardt, D; Hinton, SC; Levin, ED; March, J; Meck, WH; Rose, JE; Sparrow, E, 1996)	1.74
" Brand preference was related to cigarette use in a dose-response fashion for all subgroups, with preference highest among African American students who smoked at least half a pack of cigarettes on a daily basis."	( Smoking and preference for brand of cigarette among adolescents. Edwards, DW; Lewis, RA; Schulenberg, J; Volk, RJ, 1996)	0.29
"We performed the following studies: (1) a cross-sectional comparison of smokers and control subjects, (2) an examination of the dose-response relationship, (3) an exploration of the effect of smoking cessation (3 weeks) and nicotine patch supplementation, (4) the effect of aspirin consumption, and (5) the effects of 5 days' dosing with vitamin E (100 and 800 U), vitamin C (2 g), and their combination."	( Modulation of oxidant stress in vivo in chronic cigarette smokers. Delanty, N; FitzGerald, GA; Lawson, JA; Reilly, M, 1996)	0.48
" Dose-response curves for agonist-induced ileum contraction indicate that RJR-2403 is less than one-tenth as potent as nicotine with greatly reduced efficacy."	( RJR-2403: a nicotinic agonist with CNS selectivity I. In vitro characterization. Arrington, S; Bencherif, M; Caldwell, WS; Fowler, KW; Lippiello, PM; Lovette, ME; Reeves, L, 1996)	0.5
"Tolerance to discriminative stimulus (DS) effects of drugs, as observed by a shift of the dose-response curve to the right, has been observed with many addictive drugs (e."	( Discriminative stimulus effects of nicotine and chronic tolerance. Goldberg, SR; Schindler, CW; Shoaib, M; Thorndike, E, 1997)	0.57
"Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis."	( Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Batts, KP; Croghan, IT; Dale, LC; Hurt, RD; Lawson, GM; Offord, KP; Petersen, BT; Sandborn, WJ; Schroeder, DR; Tremaine, WJ, 1997)	1.05
" In generalization tests, rats trained with either cytisine or nicotine showed steep dose-response curves (generalization gradients) for their respective training drug."	( Discriminative stimulus properties of the nicotinic agonist cytisine. Chandler, CJ; Stolerman, IP, 1997)	0.54
" This study aimed primarily to assess sources of individual variability in nicotine and metabolite plasma levels from these dosing systems and from cigarette smoking."	( Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking. Benowitz, NL; Jacob, P; Zevin, S, 1997)	0.83
" To compensate for individual differences in clearance, individualization of nicotine dosing based on therapeutic drug monitoring with comparison to nicotine or continine levels during cigarette smoking prior to treatment may be necessary to optimize nicotine therapy."	( Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking. Benowitz, NL; Jacob, P; Zevin, S, 1997)	0.83
" In 1950, the first large-scale epidemiological studies documented that cigarette smoking induces lung cancer and described a dose-response relationship between number of cigarettes smoked and the risk for developing lung cancer."	( The changing cigarette, 1950-1995. Hoffmann, D; Hoffmann, I, 1997)	0.3
" When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained."	( Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition. Goldberg, SR; Schindler, CW; Shoaib, M, 1997)	1.74
" Initially, in phase I, 18 experiments were performed to study the dose-response curve of both the drugs."	( Combined effects of caffeine and nicotine on cardiovascular hemodynamics in canine model. Billie, M; Jain, AC; Mehta, MC, 1997)	0.58
" Other studies have not found a dose-response relationship with lower dosages of mesalamine."	( The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease. Bonapace, CR; Mays, DA, )	0.42
" At 20 degrees C, the area under the plasma concentration-time curve (AUC) of the last dosing interval was 20."	( Temperature dependency of the release and bioavailability of nicotine from a nicotine vapour inhaler; in vitro/in vivo correlation. Andersson, SB; Lunell, E; Molander, L, 1997)	0.54
" This dosing regimen was shown to mimic the arterio-venous nicotine concentration gradient typical of nicotine delivered by cigarette smoking in humans."	( Active immunization alters the plasma nicotine concentration in rats. Hieda, Y; Kane, JK; Keyler, DE; Niedbalas, RS; Pentel, PR; Raphael, DE; Ross, CA; Vandevoort, JT, 1997)	0.81
"Adult smokers were recruited to use the nicotine nasal spray for smoking cessation at a dosage of 1 to 2 mg/h."	( Nicotine nasal spray for smoking cessation: pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels. Croghan, GA; Croghan, IT; Dale, LC; Gomez-Dahl, LC; Hurt, RD; Offord, KP, 1998)	2.01
" Dose-response curves for agonist-induced ileum contraction indicate that RJR-2429 is equipotent with nicotine, having an EC30 of approximately 2 microM."	( The heterocyclic substituted pyridine derivative (+/-)-2-(-3-pyridinyl)-1-azabicyclo[2.2.2]octane (RJR-2429): a selective ligand at nicotinic acetylcholine receptors. Bencherif, M; Bhatti, BS; Caldwell, WS; Crooks, P; Fowler, K; Lippiello, PM; Lovette, ME; Reeves, L; Schmitt, JD, 1998)	0.52
" Tolerance develops with repeated use, causing the user to increase nicotine dosing through increased use and/or switching to products with higher nicotine yields."	( Smokeless tobacco: an addicting drug. Fant, RV; Henningfield, JE; Tomar, SL, 1997)	0.53
" Instructions for proper administration and dosing of the nicotine nasal spray are discussed as well as how to taper it appropriately, and how to avoid--and manage--adverse effects."	( Utilization of nicotine nasal spray in smoking cessation. Garrett, SD; Montalto, NJ, 1998)	0.9
" Transient variations in clearance due to meals would require the corresponding use of rapid drug delivery dosage forms."	( Importance of chronopharmacokinetics in design and evaluation of transdermal drug delivery systems. Benowitz, N; Gries, JM; Verotta, D, 1998)	0.3
" In phase I, 30 experiments were performed to study the dose-response curve of both the drugs."	( Combined effects of alcohol and nicotine on cardiovascular performance in a canine model. Billie, M; Jain, AC; Mehta, MC, 1998)	0.58
" First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy."	( Application of serum nicotine and plasma cotinine concentrations to assessment of nicotine replacement in light, moderate, and heavy smokers undergoing transdermal therapy. Croghan, IT; Dale, LC; Hurt, RD; Jiang, NS; Lawson, GM; Offord, KP; Schroeder, DR, 1998)	0.93
"NRT can be delivered through a number of different nicotine-containing dosage forms (e."	( Smoking cessation: Part 2--Pharmacologic approaches. Jack, HM; Popovich, NG; Wongwiwatthananukit, S, )	0.38
" (-)-Nicotine exhibited a bell-shaped dose-response relationship, and showed attenuation of response at the highest dose (5."	( Pharmacological characterization of nicotinic receptor-mediated acetylcholine release in rat brain--an in vivo microdialysis study. Imoto, M; Ohno, T; Saito, K; Tani, Y, 1998)	0.81
" Adult male rats received subcutaneous injections of either nicotine or saline during the dark period of each day on an increasing frequency (1-3 injections/day) and dosage (0."	( Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation. Rasmussen, DD, 1998)	0.87
" The dose-response relationship and possible tachyphylaxis were tested for each chemical."	( Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa. Carstens, E; Handwerker, HO; Kuenzler, N, 1998)	0.3
" Male Sprague-Dawley rats were pretreated with either subcutaneous nicotine or equivolume saline and a dose-response curve for dopaminergic pulmonary vasodilation was constructed ex vivo in isolated, salt-perfused rat lungs preconstricted with the synthetic thromboxane analogue U-46619."	( Acute nicotine pretreatment augments dopaminergic pulmonary vasodilation. Russ, RD, 1998)	1.02
" Hill analysis of the dose-response curves in cells transfected with alpha3, beta4 and alpha6 cDNAs, suggests the assembly of functional alpha3beta4alpha6 receptor, with an apparent affinity for ACh threefold lower than alpha3beta4."	( The neuronal alpha6 subunit forms functional heteromeric acetylcholine receptors in human transfected cells. Alemà, S; Ballivet, M; Barabino, B; Erkman, L; Eusebi, F; Fucile, S; Grassi, F; Matter, JM; Ragozzino, D, 1998)	0.3
" The lack of a clear dose-response relationship for the agonist and the antagonist indicates that the interaction between the NAc nicotinic system and ETOH self-administration is complex."	( Effects of nicotine and mecamylamine microinjections into the nucleus accumbens on ethanol and sucrose self-administration. Chappell, AM; Nadal, R; Samson, HH, 1998)	0.69
" High dosage nicotine treatment significantly increased the MPTP-induced loss of body weight and resulted in a significantly decreased striatal dopamine content and an increased dopamine turnover in comparison with the MPTP-treated controls at day 15."	( Effects of nicotine on hydroxyl free radical formation in vitro and on MPTP-induced neurotoxicity in vivo. Earl, CD; Ferger, B; Kuschinsky, K; Oertel, WH; Spratt, C; Teismann, P, 1998)	1.06
" The dose-response curve was bell shaped."	( Nongenomic mechanisms of glucocorticoid inhibition of nicotine-induced calcium influx in PC12 cells: involvement of protein kinase C. Chen, YZ; Huang, XY; Lou, LG; Lou, SJ; Pei, G; Qiu, J, 1998)	0.55
" Our study examined the hypothesis that transdermal nicotine, dosed up to three times the doses currently recommended for smoking cessation, would suppress nicotine intake from ad libitum smoking in a dose-dependent manner."	( Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine. Benowitz, NL; Jacob, P; Zevin, S, 1998)	0.9
" The pattern of shift of the dose-response curve for nicotine-induced convulsion in mice was determined in the presence of increasing concentrations of the anticholinergic antiparkinson drugs."	( Anti-nicotinic properties of anticholinergic antiparkinson drugs. Cui, WY; Fan, QH; Gao, ZG; Li, LJ; Liu, BY; Liu, CG, 1998)	0.55
"To determine whether an inverse dose-response relationship exists between cigarette smoking and PD among ever-smokers and ex-smokers."	( Smoking and Parkinson's disease: a dose-response relationship. Gorell, JM; Johnson, CC; Peterson, EL; Rybicki, BA, 1999)	0.3
"The inverse dose-response relationship between PD and smoking and its cessation is unlikely to be due to bias or confounding, as discussed, providing indirect evidence that smoking is biologically protective."	( Smoking and Parkinson's disease: a dose-response relationship. Gorell, JM; Johnson, CC; Peterson, EL; Rybicki, BA, 1999)	0.3
" Results from extinction tests showed that all groups of mice yielded orderly dose-response curves for nicotine (0."	( Discrimination and self-administration of nicotine by inbred strains of mice. Elmer, GI; Goldberg, SR; Naylor, C; Stolerman, IP, 1999)	0.78
" The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate."	( Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Gulsvik, A; Gustavsson, G; Paoletti, P; Rijcken, B; Russell, MA; Saracci, R; Sawe, U; Tønnesen, P, 1999)	0.89
" Nicotine increment was stable across phase, confirming reliability of the dosing method."	( Effects of menstrual phase on reactivity to nicotine. Marks, JL; Pomerleau, CS; Pomerleau, OF, )	1.3
" Brain nicotine concentration was reduced in rats immunized with CMUNic over the entire 6-min sampling period immediately following nicotine dosing (mean reduction 38%)."	( Immunization of rats reduces nicotine distribution to brain. Hieda, Y; Keyler, DE; Niedbala, RS; Pentel, PR; Raphael, DE; Ross, CA; VanDeVoort, JT, 1999)	1.05
" Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders."	( Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research. Dursun, SM; Kutcher, S, 1999)	0.92
"A MEDLINE search (1966 to present) of English language literature regarding the use of various nicotine dosage forms in the treatment of ulcerative colitis."	( Nicotine: does it have a role in the treatment of ulcerative colitis? Frazee, LA; Slyk, MP, 1997)	1.96
" With the discovery of the potential relationship between nonsmoking status and the onset of ulcerative colitis and the development of various nicotine dosage forms came the hypothesis that nicotine may play a protective role against the development of ulcerative colitis and maintenance of remission."	( Nicotine: does it have a role in the treatment of ulcerative colitis? Frazee, LA; Slyk, MP, 1997)	1.94
" dose of nicotine effected a transient, lung-specific induction of cytochrome P-450 (CYP) 1A1 in the rat, a dose-response study and assessment of the lung specificity of the induction was limited by toxicity of the acute parenteral nicotine exposure."	( Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding. Fisher, H; Fung, J; Halladay, AK; Iba, MM; Pak, YW; Sekowski, A; Thomas, PE; Wagner, GC, 1999)	0.93
"Male Wistar rats were prepared with a set of sleep recording electrodes and, following habituation to the test chamber, were used in one of three studies: a) a dose-response analysis of an acute dose of nicotine on REM sleep measured during the first 4 h after injection; b) a chronic treatment experiment; or c) a mecamylamine blockade experiment."	( Changes in sleep after acute and repeated administration of nicotine in the rat. Blanco-Centurion, C; Gonzalez-Sanchez, H; Moro-Lopez, ML; Salin-Pascual, RJ, 1999)	0.73
" In contrast, few attempts have been made to establish the dose-response relationship between nicotine and EEG parameters."	( Electroencephalographic effects of intravenous nicotine--a dose-response study. Lindgren, M; Lunell, E; Molander, L; Rosén, I; Verbaan, C, 1999)	0.78
"The aim of this study was to investigate the dose-response relationship for EEG and auditory oddball P300 parameters over a wide range of intravenously infused nicotine doses."	( Electroencephalographic effects of intravenous nicotine--a dose-response study. Lindgren, M; Lunell, E; Molander, L; Rosén, I; Verbaan, C, 1999)	0.76
" Participants in the low-dose group exhibited a significant leftward shift in the dose-response function for discrimination performance, which is concordant with previous preclinical and human drug discrimination studies that assessed the effects of training dose."	( Effects of training dose on the relationship between discriminative-stimulus and self-reported drug effects of d-amphetamine in humans. Kollins, SH; Rush, CR, 1999)	0.3
" Because of these properties, proliposomes appear to be a potential alternative to liposomes in design and fabrication of liposomal dosage forms."	( Future drug delivery research in South Korea. Chung, SJ, 1999)	0.3
" Within the dose ranges tested, both nicotine and nornicotine yielded relatively flat dose-response functions."	( Nornicotine is self-administered intravenously by rats. Bardo, MT; Crooks, PA; Dwoskin, LP; Green, TA, 1999)	1.2
" The dose-response parameters of recombinant mouse adult neuromuscular acetylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine, muscarine and oxotremorine were measured."	( Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists. Akk, G; Auerbach, A, 1999)	0.5
" The different nicotine replacement products approximately double the long-term success rate with a dose-response effect, but with an equal efficacy of the different administration forms, so there is no long-term effect of a combination of two products, and they have only mild side-effects."	( Smoking cessation: nicotine replacement, gums and patches. Tønnesen, P, 1999)	0.98
" These dosage forms of nicotine appear to circumvent some of the shortcomings of transdermal patches (i."	( Prolonged delivery of nicotine in rats via nasal administration of proliposomes. Chung, BC; Chung, SJ; Jung, BH; Lee, MH; Shim, CK, 2000)	0.93
" Adequate dosage regimens should be stressed in order to avoid under-dosing, which is common with NRT."	( Maximizing help for dissonant smokers. Kunze, M, 2000)	0.31
"This study is the first to demonstrate associative tolerance to nicotine's analgesic effects as a shift in the dose-response curve (DRC) to the right."	( Dose-response analyses of associative tolerance to nicotine analgesia in the rat: tail-flick and hot-plate tests. Cepeda-Benito, A; Erath, SA; Reynoso, J, 2000)	0.8
" F3 (30 nM) rapidly and reversibly blocked inward currents generated by pulse applications of nicotine, shifting the dose-response curve to the right in a parallel fashion without changing the maximum response."	( Antagonism of nicotinic receptors of rat chromaffin cells by N,N, N-trimethyl-1-(4-trans-stilbenoxy)-2-propylammonium iodide: a patch clamp and ligand binding study. Clementi, F; Di Angelantonio, S; Gotti, C; Moretti, M; Nistri, A, 2000)	0.53
" Thirty-two reports (29 studies) evaluated adverse effects of drug therapy; many of the side effects associated with stimulant use appear to be relatively mild and of short duration and to respond to dosing or timing adjustments."	( Treatment of attention-deficit/hyperactivity disorder. Boyle, M; Cunningham, C; Jadad, AR; Kim, M; Schachar, R, 1999)	0.3
"The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; and to determine whether combinations of NRT are more effective than one type alone."	( Nicotine replacement therapy for smoking cessation. Fowler, G; Lancaster, T; Mant, D; Silagy, C, 2000)	1.97
" Dose-response curves were constructed before and during nicotine coinfusion at a rate of 40 ng/min, reproducing a plasma concentration of 15 ng/mL."	( Nicotine impairs endothelium-dependent dilatation in human veins in vivo. Benowitz, NL; Blaschke, TF; Chalon, S; Hoffman, BB; Moreno, H, 2000)	1.99
" In the presence of 10 microM SP, the dose-response relationship of the peak levels shifted downward."	( Effects of substance P on nicotine-induced intracellular Ca2+ dynamics in bovine adrenal chromaffin cells. Habara, Y; Kanno, T; Suzuki, S, 1999)	0.6
"5% for 10 days); (2) dose-response tests for nicotine (0."	( Sex differences in nicotine substitution to a pentylenetetrazol discriminative stimulus during ethanol withdrawal in rats. Gatch, MB; Jung, ME; Lal, H; Wallis, CJ, 2000)	0.9
" (2) For nicotine dose-response tests, more male rats (70%) selected the PTZ lever than OVX (37."	( Sex differences in nicotine substitution to a pentylenetetrazol discriminative stimulus during ethanol withdrawal in rats. Gatch, MB; Jung, ME; Lal, H; Wallis, CJ, 2000)	1.05
" (5) There is a strong dose-response relationship between the intensity of tobacco dependence counseling and its effectiveness."	( A clinical practice guideline for treating tobacco use and dependence: A US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. , 2000)	0.31
"The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies."	( Nicotine replacement therapy for smoking cessation. Fowler, G; Lancaster, T; Mant, D; Silagy, C, 2000)	1.97
" The current study examined the immunogenicity of a nicotine conjugate vaccine during continued nicotine dosing in rats, and its effects on nicotine distribution to brain."	( Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain. Ennifar, S; Fattom, A; Hieda, Y; Keyler, DE; Pentel, PR, 2000)	0.88
" Dose-response curves to bradykinin and sodium nitroprusside were obtained to test the endothelium-dependent and endothelium-independent vasorelaxation before and during the use of a nicotine (21 mg) patch."	( Transdermal nicotine mimics the smoking-induced endothelial dysfunction. Cittadino, M; Moreno, H; Rocha, JC; Sabha, M; Tanus-Santos, JE; Toledo, JC, 2000)	0.88
" 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)	0.49
"5, using a dosage regimen that maintains plasma levels similar to those found in smokers or in users of the transdermal nicotine patch."	( Persistent and delayed behavioral changes after nicotine treatment in adolescent rats. Seidler, FJ; Slotkin, TA; Trauth, JA, 2000)	0.77
" two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs."	( Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance. Dibb, WD; Gilbert, DG; Hiyane, SG; Plath, LC, 2000)	0.9
" The nicotine discrimination was acquired successfully and nicotine yielded a steep dose-response curve."	( Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice. Gommans, J; Shoaib, M; Stolerman, IP, 2000)	1.06
" Overall, the results suggest that nicotine's effects are modified by environmental conditions, and that nicotine administration at this dosage and in this particular rat strain results in anxiogenic effects."	( Nicotine administration interacts with housing conditions to alter social and non-social behaviors in male and female Long-Evans rats. Faraday, MM; Grunberg, NE; Scheufele, PM, 2000)	2.03
" Dosing was established according to baseline nicotine dependence, scored on the Fagerström Tolerance Questionnaire (FTQ): FTQ > or = 7, two tablets/hour (maximum 40/day); FTQ < 7, one tablet/hour (maximum 20/day)."	( A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation. Hirsch, JM; Nilsson, F; Wallström, M, 2000)	0.8
" Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch."	( Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Clark, DB; Di Marino, ME; Elash, CA; Gwaltney, CJ; Liu, KS; Paton, SM; Paty, JA; Shiffman, S, 2000)	0.55
"These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence, when symptoms are at their peak, and when relapse is most likely."	( Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Clark, DB; Di Marino, ME; Elash, CA; Gwaltney, CJ; Liu, KS; Paton, SM; Paty, JA; Shiffman, S, 2000)	0.55
" The maximum change in systolic blood pressure occurred 5 minutes after dosing and was significantly related to nicotine administration (7."	( Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function. Fishbein, L; Flotte, T; Hutson, A; O'Brien, P; Stacpoole, PW; Theriaque, D, 2000)	0.77
" In rats performing below criterion (<80% correct, >20% omissions to a 1-s visual stimulus), subchronic dosing with nicotine (0."	( Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task. Grottick, AJ; Higgins, GA, 2000)	0.52
" Dose-response curves for nicotine (0."	( The development and expression of locomotor sensitization to nicotine in the presence of ibogaine. Shoaib, M; Stolerman, IP; Zubaran, C, 2000)	0.85
"When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance."	( Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers. Heishman, SJ; Henningfield, JE, 2000)	0.89
" This dosage of nicotine administered during pregnancy to same rats was shown to result in increased vertical activity in the male offspring [Tizabi Y, Russell LT, Nespor SM, Perry DC, Grunberg NE."	( Prenatal nicotine exposure is associated with an increase in [125I]epibatidine binding in discrete cortical regions in rats. Perry, DC; Tizabi, Y, 2000)	1.07
" Measures of total nicotine absorbed (AUC), maximum plasma nicotine concentration (C(max)) and minimum plasma nicotine concentration (C(min)), were higher for the 21-mg, 24-h patches than for the 15-mg, 16-h patch during both the first day of dosing and during the modeled steady-state period (48-72 h after initial application)."	( A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches. Fant, RV; Henningfield, JE; Reitberg, DP; Shiffman, S; Strahs, KR, 2000)	0.85
" Chronic tolerance was determined by a shift to the right, or flattening, of the dose-response curve relative to the curve for nonsmokers."	( Dissociation of nicotine tolerance from tobacco dependence in humans. Broge, M; Cherry, C; Fonte, C; Gerlach, D; Grobe, JE; Perkins, KA; Sanders, M; Vender, J; Wilson, A, 2001)	0.66
" After the first week of pregnancy, the experimental group of rats were given nicotine intraperitoneally in a dosage of 2 mg/kg for two weeks."	( Teratogenic effects of nicotine on rat skin. Deveci, E; Eralp, A; Inalöz, HS; Inalöz, SS, 2000)	0.85
" Dose-response curves to bradykinin (0."	( Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats. Calegari, V; do Prado, JF; Moreno, H; Paganelli, MO; Tanus-Santos, JE; Toledo, JC, 2001)	0.62
" Dosing order was determined randomly and counterbalanced."	( Subjective and discriminative stimulus effects of two de-nicotinized cigarettes with different tar yields. Downey, KK; Schuh, KJ; Schuh, LM; Stamat, HM, 2001)	0.31
" In the elevated plus-maze, the time-course and the dose-response curve to nicotine were investigated."	( Social isolation modifies nicotine's effects in animal tests of anxiety. Cheeta, S; File, SE; Irvine, E, 2001)	0.84
"00 mg of nicotine tartrate/kg body wt; these dosage regimens produced maternal serum nicotine concentrations of 19 +/- 6 and 35 +/- 8 ng/ml, respectively."	( Threshold levels of maternal nicotine impairing protective responses of newborn rats to intermittent hypoxia. Fewell, JE; Ng, VK; Smith, FG, 2001)	1.02
"A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors."	( Behavioral and neural consequences of prenatal exposure to nicotine. Ernst, M; Moolchan, ET; Robinson, ML, 2001)	0.55
" twice daily on 5 consecutive days to study dose-response effects of nicotine on adult spontaneous and nicotine-induced motor behaviour."	( Neurobehavioural defects in adult mice neonatally exposed to nicotine: changes in nicotine-induced behaviour and maze learning performance. Ankarberg, E; Eriksson, P; Fredriksson, A, 2001)	0.79
"Oral nicotine dosing forms such as nicotine gum have been found to be effective in helping smokers to stop."	( Effect of oral nicotine dosing forms on cigarette withdrawal symptoms and craving: a systematic review. Shiffman, S; West, R, 2001)	1.18
"Nicotine dosage regimen can influence the nicotine mechanism of action: an instantaneous delivery at an individually selected time seems to inhibit the onset of craving while constant delivery at a pre-defined time seems to attenuate the craving."	( Population pharmacokinetic-pharmacodynamic model of craving in an enforced smoking cessation population: indirect response and probabilistic modeling. Bye, A; Gomeni, R; Iavarone, L; Squassante, L; Teneggi, V, 2001)	1.75
" The MTTB is a suitable, well tolerated technique for the detection of transdermally applied compounds in defined subepidermal tissue layers and could therefore become a valuable tool in the development and assessment of transdermal dosage forms."	( Application of the minimal trauma tissue biopsy to transdermal clinical pharmacokinetic studies. Brunner, M; Eichler, HG; Mayer, BX; Müller, M; Schrolnberger, C, 2001)	0.31
" In general, the dose-response characteristics were strikingly biphasic in nature and were independent of both the target tissue and chemoattractant agent."	( Cell migration/chemotaxis: biphasic dose responses. Calabrese, EJ, 2001)	0.31
" The applied dosage and regimen of nicotine administration did not change rat pain threshold (flinch-jump test)."	( The anxiolytic-like effect of nicotine undergoes rapid tolerance in a model of contextual fear conditioning in rats. Członkowska, AI; Maciejak, P; Płaznik, A; Rokicki, D; Siemiatkowski, M; Sienkiewicz-Jarosz, H; Szyndler, J, )	0.7
"Initially, in phase 1, 30 experiments were performed to study the dose-response curve of both drugs."	( Combined effects of cocaine and nicotine on cardiovascular performance in a canine model. Billie, MD; Jain, AC; Mehta, MC, 2001)	0.59
"Hemodynamic parameters observed were Phase I: Dose-response curve established the IV bolus dose of cocaine 2 mg/kg and nicotine 50 microg/kg."	( Combined effects of cocaine and nicotine on cardiovascular performance in a canine model. Billie, MD; Jain, AC; Mehta, MC, 2001)	0.8
"With the dosage and the period of treatment chosen, transdermal nicotine patches are not effective as an add-on treatment for symptoms of PD."	( Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Hagenah, JM; Jacobs, H; Sieberer, M; Vieregge, A; Vieregge, P, 2001)	0.93
"The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies."	( Nicotine replacement therapy for smoking cessation. Fowler, G; Lancaster, T; Mant, D; Silagy, C; Stead, L, 2001)	1.98
" In less acute cases this is not needed; (iii) ensure dosing does not exceed the manufacturer's recommendation; (iv) warn patients to stop using NRT if they relapse to smoking; and (v) target motivated smokers (i."	( Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals. Hajek, P; McRobbie, H, 2001)	1.75
" The results with Chinese-Americans may have implications for dosing with nicotine medications to aid smoking cessation in Chinese- American smokers and perhaps in other Asian smokers."	( Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. Benowitz, NL; Herrera, B; Jacob, P; Pérez-Stable, EJ, 2002)	0.81
" To test this hypothesis, we injected nicotine intraperitoneally in alpha7 mutant mice and found that the dose-response curve for nicotine-induced seizures was similar in the alpha7 +/+, alpha7 +/- and alpha7 -/- mice."	( Absence of alpha7-containing neuronal nicotinic acetylcholine receptors does not prevent nicotine-induced seizures. Bassetto, L; Broide, R; De Biasi, M; Franceschini, D; Gotti, C; Paylor, R; Salas, R, 2002)	0.81
" The studies described here evaluated the potential role of these polymorphisms in regulating sensitivity to nicotine by constructing dose-response curves for the effects of nicotine on six responses in the LSxSS RI strains."	( Variability in response to nicotine in the LSxSS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes. Collins, AC; Marks, MJ; Romm, E; Stitzel, JA; Tritto, T, 2002)	0.82
"8 mg/kg) rapidly and exhibited steep dose-response curves."	( The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion. Changeux, JP; Gommans, J; Grailhe, R; Morley, A; Shoaib, M; Stolerman, IP, 2002)	0.57
" Because nicotine vaccines target the drug rather than the brain, and the antibodies themselves do not cross the blood-brain barrier, immunization should circumvent the central nervous system side effects that limit the usable dosage of other medications for tobacco dependence."	( A vaccine for nicotine dependence: targeting the drug rather than the brain. Malin, D; Pentel, P, 2002)	1.09
" Adverse events associated with the use of bupropion SR at the recommended dosage of 150mg twice daily in clinical trials most commonly included insomnia, headache, dry mouth, nausea and anxiety; insomnia and anxiety are also recognised as symptoms of nicotine withdrawal."	( Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Aubin, HJ, 2002)	0.5
"Acute nicotine treatment produced an inverted U-shaped dose-response function with lower doses increasing and the highest dose decreasing the number of cocaine infusions obtained during a session."	( Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats. Bechtholt, AJ; Mark, GP, 2002)	1.05
"Because the taste of nicotine gum has impeded compliance with dosing recommendations, nicotine gum with improved taste (mint, orange) was developed and marketed."	( Flavor improvement does not increase abuse liability of nicotine chewing gum. Eissenberg, TE; Fant, RV; Henningfield, JE; Houtsmuller, EJ; Stitzer, ML, 2002)	0.88
" These include the currently available dosage forms of nicotine replacement therapy (gum, patch, nasal spray, and inhaler) and bupropion."	( Managing nicotine addiction. Hatsukami, DK; Kotlyar, M, 2002)	0.98
" Accordingly, we studied the effect of NO generated from S-nitroso-N-acetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (Po(2) approximately 30 Torr)."	( Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms. Del Rio, R; Iturriaga, R; Mosqueira, M; Rey, S; Valdés, V, 2003)	0.49
"The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies."	( Nicotine replacement therapy for smoking cessation. Fowler, G; Lancaster, T; Mant, D; Silagy, C; Stead, L, 2002)	1.98
"Nicotine can induce PBMCs to secrete more TNF, and the magnitude of the effect is strongly related to the dosage of nicotine, but a great dose of nicotine will inhibit the production of TNF."	( [Effect of nicotine on the secretion of TNF of human peripheral blood mononuclear cells in vitro]. Lei, GH; Li, KH; Zhou, JN, 2002)	2.15
"6 mg/kg) was dose-related, but the dose-response relationship was not dependent upon the presence of midazolam."	( Nicotine trace discrimination in rats with midazolam as a mediating stimulus. Mariathasan, EA; Stolerman, IP, 2003)	1.76
"Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates."	( Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. Addo, F; Croghan, IT; Hurt, RD; Kardinal, CG; Knost, JA; Krook, JE; Loprinzi, CL; Michalak, JC; Morton, RF; Novotny, PJ; Porter, PA; Schaefer, PL; Sloan, JA; Stella, PJ; Tirona, MT, 2003)	1.97
" The Nicotine Maintenance group received 21 mg transdermal nicotine for 8 additional weeks; the Standard Treatment group followed a tapered dosing regimen."	( Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. Marks, JL; Mehringer, AM; Namenek Brouwer, RJ; Pomerleau, CS; Pomerleau, OF; Saules, KK; Snedecor, SM, 2003)	1.24
" In addition, nicotine in low dosage (10 microM) rescued the decreased rates of cell viability and inhibited the production of lipid peroxidation resulted from H(2)O(2) and Abeta in the cultured cells."	( Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Guan, ZZ; Nordberg, A; Yu, WF, 2003)	1.03
" Dose-response curves were generated by plotting the change in the bone vascular resistance index (mmHg/bone perfusion units) evoked by each dose of agonist."	( Two week nicotine treatment selectively increases bone vascular constriction in response to norepinephrine. Feitelson, JB; Fleming, JT; Roberts, CS; Rowell, PP, 2003)	0.74
" Theoretical advantages of OT-NIC include that it does not require special chewing methods or interfere with dental work, it provides sensory oral effect, and it can be dosed to effect."	( Efficacy of oral transmucosal nicotine lozenge for suppression of withdrawal symptoms in smoking abstinence. Leischow, SJ; Muramoto, ML; Ranger-Moore, J, 2003)	0.61
" Both markers co-varied with a similar dose-response and time course after the nicotine-treatment."	( Nicotine-induced inflammatory decreasing effect on passive skin arthus reaction in paraventricular nucleus-lesioned wistar rats. Kita, T; Kubo, K; Nakashima, T; Nakatani, T; Narushima, I; Tanaka, T, 2003)	1.99
"This was a prospective study of the effects of maternal smoking during pregnancy on newborn neurobehavior, including dose-response relationships using self-report and a bioassay of nicotine exposure."	( Smoking during pregnancy and newborn neurobehavior. LaGasse, LL; Law, KL; Lester, BM; Liu, J; Niaura, R; Stroud, LR, 2003)	0.51
" Dose-response relationships with NNNS scores were computed for maternal salivary cotinine and maternal report of number of cigarettes per day during pregnancy."	( Smoking during pregnancy and newborn neurobehavior. LaGasse, LL; Law, KL; Lester, BM; Liu, J; Niaura, R; Stroud, LR, 2003)	0.32
" Dose-response relationships could indicate neonatal withdrawal from nicotine."	( Smoking during pregnancy and newborn neurobehavior. LaGasse, LL; Law, KL; Lester, BM; Liu, J; Niaura, R; Stroud, LR, 2003)	0.55
"Bupropion produced a biphasic dose-response pattern at both nicotine infusion doses, increasing infusions at low bupropion doses and decreasing infusions at high bupropion doses."	( Effect of bupropion on nicotine self-administration in rats. Bardo, MT; Dwoskin, LP; Neugebauer, N; Rauhut, AS, 2003)	0.87
" A dose-response relationship was observed between the sensations and cigarette smoking."	( Sensations from initial exposure to nicotine predicting adolescent smoking in China: a potential measure of vulnerability to nicotine. Azen, S; Chen, X; Gallaher, P; Gong, J; Liu, C; Ph D, AJ; Shakib, S; Shan, J; Spruijt-Metz, D; Stacy, A; Unger, J; Zheng, H, 2003)	0.59
" 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
" The present study determined the dose-response for nicotine (0."	( Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex. Cass, WA; Dwoskin, LP; Middleton, LS, 2004)	0.57
"A reverse phase HPLC method using C18 column has been developed for the quantitative estimation of nicotine in the bulk material and formulations (extended release and immediate release dosage forms)."	( A validated high performance liquid chromatographic method for analysis of nicotine in pure form and from formulations. Garg, S; Kakariya, RB; Tambwekar, KR, 2003)	0.77
" The multiple-dose study applying different dosing intervals (i."	( Pharmacokinetics of a nicotine polacrilex lozenge. Choi, JH; Dresler, CM; Norton, MR; Strahs, KR, 2003)	0.63
"Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function ( r=0."	( The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat. Froestl, W; Markou, A; Paterson, NE, 2004)	2.01
") were determined alone and on the dose-response curve for alcohol (0."	( Comprehensive deficits in performance of an attentional task produced by co-administering alcohol and nicotine to rats. Bizarro, L; Patel, S; Stolerman, IP, 2003)	0.53
" A subject's response to nicotine on each measure was determined by the slope of his or her dose-response curve (0, 10, 20 microg/kg nicotine)."	( Common factors across acute subjective effects of nicotine. Jetton, C; Keenan, J; Perkins, KA, 2003)	0.88
", self-reported effects), cardiovascular, and performance measures were assessed following each of four dosing trials of nicotine (20 microg/kg) on three sessions and of placebo on one session."	( The consistency of acute responses to nicotine in humans. Conklin, CA; Fonte, C; Jetton, C; Perkins, KA; Stolinski, A, 2003)	0.8
" The fluorescent receptors resembled wild-type receptors in maximal responses to ACh, dose-response relations, ACh-induced Ca2+ influx, and somatic and dendritic distribution."	( Assembly of alpha4beta2 nicotinic acetylcholine receptors assessed with functional fluorescently labeled subunits: effects of localization, trafficking, and nicotine-induced upregulation in clonal mammalian cells and in cultured midbrain neurons. Dickinson, ME; Fraser, SE; Jareb, M; Labarca, C; Lester, HA; McKinney, S; Nashmi, R, 2003)	0.52
" These mGluRs are functionally active on catecholamine (CA) secretion in chromaffin cells because both (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and the specific agonist of Group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), were able to stimulate the release of CAs (adrenaline and noradrenaline) in a dose-response manner."	( Expression and functional properties of group I metabotropic glutamate receptors in bovine chromaffin cells. Aránguez, I; Arce, C; Del Campo, AB; Figueroa, S; González, MP; López, E; Oset-Gasque, MJ, 2004)	0.32
" Several studies have found a dose-response relationship between the number of cigarettes smoked each day and breastfeeding intention, initiation, and duration that persists after adjusting for confounding factors."	( Does maternal smoking have a negative physiological effect on breastfeeding? The epidemiological evidence. Amir, LH; Donath, SM, 2003)	0.32
" The genotypes exhibited similar steep dose-response curves for nicotine discrimination."	( The role of nicotinic receptor alpha 7 subunits in nicotine discrimination. Bizarro, L; Chamberlain, S; Fernandes, C; Schalkwyk, L; Stolerman, IP, 2004)	0.81
" Dosing repeatedly with The Straw led to greater nicotine levels that continued to increase with additional dosing."	( Tolerability and pharmacokinetics of single and repeated doses of nicotine with The Straw, a novel nicotine replacement product. D'Orlando, KJ; Fox, BS, 2004)	0.81
" Incorporation of tritiated thymidine into whole brain DNA demonstrated that the nicotine treatment did not cause increased rates of whole brain mitosis, suggesting that the dosage regimen did not elicit a cytotoxic, wound-healing, response of differentiating cells."	( Exposure to low concentrations of nicotine during cranial nerve development inhibits apoptosis and causes cellular hypertrophy in the ventral oculomotor nuclei of the chick embryo. Corbin Downey, L; Ewald, KW; Hatley, ME; Wielgus, JJ; Wilson, KC; Yeilding, RH, 2004)	0.83
" The clinician prescribing a dosage for a patient has to take all these parameters into account to make an accurate choice."	( [Usefulness of biological markers in evaluation of smoking]. Asnafi-Farhang, S; Diviné, C; Lagrue, G; Larramendy, C, 2004)	0.32
" A dose-response curve for nicotine was also generated using two additional groups of ten adolescent and ten adult male rats."	( Differential behavioral effects of nicotine exposure in adolescent and adult rats. Kelley, AE; Landry, CF; Schochet, TL, 2004)	0.9
" Dose-response testing revealed differences in adolescent responsivity to nicotine in measures of rearing, but not ambulation."	( Differential behavioral effects of nicotine exposure in adolescent and adult rats. Kelley, AE; Landry, CF; Schochet, TL, 2004)	0.83
" Additional work with intermittent dosing schedules is required to characterize optimal clinical and cognitive effects with nicotine treatment."	( Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome. Batth, S; Boisjoli, A; Howson, AL; Ilivitsky, V; Jaworski, M; Knott, VJ; Mahoney, C, 2004)	0.79
" For all mice, nicotine consumption and serum cotinine levels increased in a dose-dependent manner, and the volume of nicotine intake (ml), percent nicotine intake, and nicotine dosage (mg/kg) on the last day of the experiment were positively correlated with cotinine levels."	( Sex differences in voluntary oral nicotine consumption by adolescent mice: a dose-response experiment. Kamens, HM; Klein, LC; Stine, MM; Vandenbergh, DJ; Whetzel, CA, 2004)	0.96
" Similarly to what has been reported concerning nicotine, the dose-response curve of epibatidine to increase the dopamine output in the caudate-putamen was bell-shaped and clearly differed from that in the accumbens."	( Comparison of the effects of nicotine and epibatidine on the striatal extracellular dopamine. Ahtee, L; Janhunen, S, 2004)	0.87
" The dose-response curves for acetylcholine and nicotine were hyperbolic and bell-shaped, respectively."	( Differential inhibition of nicotine- and acetylcholine-evoked currents through alpha4beta2 neuronal nicotinic receptors by tobacco cembranoids in Xenopus oocytes. Eaton, MJ; Eterović, VA; Ospina, CA; Rodríguez, AD, 2004)	0.88
"The aims of this review were:to determine the effectiveness of the different forms of NRT (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; to determine its effectiveness compared to other pharmacotherapies."	( Nicotine replacement therapy for smoking cessation. Fowler, G; Lancaster, T; Mant, D; Silagy, C; Stead, L, 2004)	1.77
" One cold air trial was performed following a NIC dosing using a 21-mg transdermal patch while the other trial was performed after a placebo (PL) treatment."	( Nicotine effects on thermoregulatory responses of men and women during acute cold exposure. Blegen, M; Caine-Bish, N; Cheatham, CC; Glickman, EL; Potkanowicz, ES, 2004)	1.77
" Exploration of the dose-response relationship indicates that acute administration offers the most likely success, reducing tremor and improving cognitive performance amongst others."	( In vitro evidence supporting the therapeutic role of nicotine against neurodegeneration. Linert, W; Williams, E, )	0.38
" Following the acute dose-response curve, mice received saline followed by 5 days of 20."	( Long-term, low-level adolescent nicotine exposure produces dose-dependent changes in cocaine sensitivity and reward in adult mice. Kelley, BM; Rowan, JD, )	0.41
" In contrast to nicotine replacement therapy and bupropion, SR141716 did not have nicotine-like discriminative effects and did not alter the dose-response curve for nicotine discrimination."	( Rimonabant, a CB1 antagonist, blocks nicotine-conditioned place preferences. Goldberg, SR; Le Foll, B, 2004)	0.94
"We have studied the relationship between urinary cotinine and other tobacco markers to assess the relevance of urinary cotinine in the dosage of nicotine substitutes."	( [Usefulness of biological markers in the evaluation of smoking at the first visit of a smoking cessation program]. Favreau, M; Ingrand, P; Meurice, JC; Mura, P; Underner, M, 2004)	0.52
" It becomes useful if the CO level is between 15 and 34 ppm, as CO level in itself is insufficient to determine the dosage of nicotine substitutes."	( [Usefulness of biological markers in the evaluation of smoking at the first visit of a smoking cessation program]. Favreau, M; Ingrand, P; Meurice, JC; Mura, P; Underner, M, 2004)	0.53
" We have performed a dose-response study for intrahippocampal nicotine (CA1) on acquisition and extinction of the lever-press response and antagonization test by co-administration of mecamylamine."	( Intrahippocampal nicotine in alcohol drinking rats--effects on lever-press response. Darbra, S; Ferré, N; García-Rebollo, Y, 2005)	0.91
" In the present study, male Wistar rats exposed a relatively low dosage of nicotine (0."	( Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor. Hernandez, CM; Terry, AV, 2005)	0.98
" Both agents produced a marked downward shift in the nicotine dose-response curve."	( Drug discrimination analysis of NMDA receptor channel blockers as nicotinic receptor antagonists in rats. Bespalov, AY; Danysz, W; Zakharova, ES, 2005)	0.58
" A smoker who compensates only incompletely for nicotine may thus obtain a higher dosage of a specific smoke toxicant from a lower-tar cigarette than from a higher-tar cigarette."	( Incomplete compensation does not imply reduced harm: yields of 40 smoke toxicants per milligram nicotine in regular filter versus low-tar cigarettes in the 1999 Massachusetts Benchmark Study. Harris, JE, 2004)	0.8
" When the two groups were compared for response to nasal spray following 5 days' abstinence, smokers in the "yes" group were marginally more likely to have signaled experiencing at least one pleasurable buzz and rated "pleasurable sensation from spray" on a 100-mm visual analogue scale administered 10 min after nicotine dosing significantly higher than were those in the "no" group."	( Validation of retrospective reports of early experiences with smoking. Cameron, OG; Mehringer, AM; Pomerleau, CS; Pomerleau, OF; Snedecor, SM, 2005)	0.5
" After 39 days of exposure to this regimen, the dose-response curves were re-determined."	( Tolerance to nicotine in mice lacking alpha7 nicotinic receptors. Fernandes, C; Naylor, C; Quarta, D; Stolerman, IP, 2005)	0.7
" When dose-response curves for nicotine (0."	( Tolerance to nicotine in mice lacking alpha7 nicotinic receptors. Fernandes, C; Naylor, C; Quarta, D; Stolerman, IP, 2005)	0.98
" Prior nicotine treatment enhanced the dose-response to cocaine."	( Periadolescent nicotine exposure causes heterologous sensitization to cocaine reinforcement. Davis, BJ; McMillen, BA; Soderstrom, K; Williams, HL, 2005)	1.14
" There was also evidence indicating that dose-response relationships existed between prenatal exposure to marijuana and offspring's use of cigarettes and marijuana."	( Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Fried, PA; Porath, AJ, )	0.13
" Among the factors contributing to the low utilization of nicotine medications are the inadequacies of the current dosage strengths and formulations of existing medications, smokers' perceptions of the high cost of the drugs, and concerns that many smokers have about safety and efficacy of nicotine medications."	( Impact of nicotine replacement therapy on smoking behavior. Cummings, KM; Hyland, A, 2005)	0.98
" Drug Phase I revealed dose-response differences between adolescent and adult female rats."	( Adolescent and adult female rats differ in sensitivity to nicotine's activity effects. Elliott, BM; Faraday, MM; Grunberg, NE; Phillips, JM, 2005)	0.57
" These data comment on the safety of vaccination against nicotine during pregnancy, and suggest that vaccination may reduce the distribution of nicotine to fetal brain under some nicotine dosing conditions."	( Reduced nicotine distribution from mother to fetal brain in rats vaccinated against nicotine: time course and influence of nicotine dosing regimen. Bramwell, TJ; Calvin, AD; Dufek, MB; Keyler, DE; Le, CT; LeSage, MG; Pentel, PR; Raphael, DE; Ross, CA, 2005)	1.01
" The aortic calcification was significantly attenuated by subcutaneous administration of ghrelin 30 and 300 nmol kg(-1) day(-1) for 4 weeks, and the latter dosage was more potent than the former."	( Ghrelin blunted vascular calcification in vivo and in vitro in rats. Cao, J; Chang, L; Jiang, W; Li, GZ; Pan, CS; Tang, CS; Zhao, J, 2005)	0.33
" via osmotic minipumps that delivered various nicotine dosage regimens, some including 24-h nicotine-free periods, to manipulate pattern of exposure."	( Dose, duration, and pattern of nicotine administration as determinants of behavioral dependence in rats. Balster, RL; Beardsley, PM; Vann, RE, 2006)	0.88
" These subjects were separated into two groups, desensitizers (DZ) and nondesensitizers (NDZ), based upon performance in the repetitive dosing drug discrimination paradigm."	( Evidence of cellular nicotinic receptor desensitization in rats exhibiting nicotine-induced acute tolerance. Gross, DF; James, JR; Lapp, LN; Philibin, SD; Robinson, SE; Rosecrans, JA; Vann, RE, 2006)	0.56
"This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD)."	( Development of transdermal system containing nicotine by using sustained release dosage design. Tirnaksiz, F; Yuce, Z, 2005)	0.81
" Dosage of cotinine in urine is of easier determination than that of other metabolites in assessing exposure to smoking, although carboxyhaemoglobin levels seem to be a qualitative, but not quantitative factor to estimate either the degree of cardiovascular damage or the level of exposure."	( Biochemical markers of cardiovascular damage from tobacco smoke. Leone, A, 2005)	0.33
" Initially, we established a dose-response relationship for the acute and chronic haloperidol and DOI-induced HTR."	( Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome. Hayslett, RL; Tizabi, Y, 2005)	0.64
" Such a hyposensitivity did not develop after a single or multiple (at short intervals) dosing with oxotremorine (OXO), a direct muscarinic agonist, which suggests that it was not mediated by muscarinic receptors."	( Behavioral sensitivity to amphetamine or scopolamine after acute administration of nicotine in the rat. Gralewicz, S; Lutz, P, 2005)	0.55
" Dose-response relationships were most clearly observed for head rush and drug high."	( Does nicotine do what we think it does? A meta-analytic review of the subjective effects of nicotine in nasal spray and intravenous studies with smokers and nonsmokers. Kalman, D; Smith, SS, 2005)	0.84
" Extracted dose of nicotine, area under the venous plasma concentration-time curve (AUC), maximum plasma nicotine concentration (Cmax) of the last (12th) dosing interval, and the Cmax and AUC ratios versus Nicorette were calculated."	( Steady-state nicotine plasma levels following use of four different types of Swedish snus compared with 2-mg Nicorette chewing gum: a crossover study. Lunell, E; Lunell, M, 2005)	1.03
") did not produce any nicotine-like discriminative effects and did not produce any shift in the dose-response curve for nicotine discrimination."	( Ethanol does not affect discriminative-stimulus effects of nicotine in rats. Goldberg, SR; Le Foll, B, 2005)	0.89
" 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)	0.51
" This suggests a rightward shift in the dose-response curve, namely, a reduced efficacy of nicotine."	( Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats. Adriani, W; Deroche-Gamonet, V; Laviola, G; Le Moal, M; Piazza, PV, 2006)	0.79
" The results indicated that the C57BL/6J (B6) were insensitive to nicotine over the entire dose-response curve (0."	( Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic mice. Boyle, AE; Gill, KJ, 2005)	0.82
" The model implies distinct thresholds on the dosage and duration for the acquisition and persistence of nicotine addiction."	( A neurocomputational hypothesis for nicotine addiction. Changeux, JP; Dehaene, S; Gutkin, BS, 2006)	0.82
"Adolescents did not display the decreases in brain reward function observed in adults experiencing withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to adults regardless of the dosing procedure used."	( Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction. Bruijnzeel, AW; Goldberger, BA; Koob, GF; Markou, A; Merves, ML; O'Dell, LE; Parsons, LH; Richardson, HN; Smith, RT, 2006)	0.92
" There are also populations for whom special product and dosage considerations are warranted to maximise treatment safety."	( Tailoring nicotine replacement therapy: rationale and potential approaches. McClure, JB; Swan, GE, 2006)	0.74
" A dose-response function for nicotine was then established."	( Intravenous self-administration of nicotine is altered by lesions of the posterior, but not anterior, pedunculopontine tegmental nucleus. Alderson, HL; Latimer, MP; Winn, P, 2006)	0.9
" Dose-response curves for ouabain, a specific Na(+),K(+)-ATPase inhibitor, were obtained to ascertain which Na(+),K(+)-ATPase isoform(s) is involved."	( On the functional interaction between nicotinic acetylcholine receptor and Na+,K+-ATPase. Drabkina, TM; Eaton, MJ; Kravtsova, VV; Krivoi, II; Mandel, F; Skatchkov, SN; Vasiliev, AN, 2006)	0.33
" This premise was further supported by experiments showing that nicotine dosing decreased the elevated dopamine turnover that occurs after nigrostriatal damage."	( Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. Chen, L; Langston, JW; McCallum, SE; Parameswaran, N; Quik, M; Xie, X, 2006)	0.94
" Independent scientific research has suggested that the nicotine dosing characteristics, hence the addiction potential of cigarettes, may be determined in part by the amount of free-base nicotine in cigarette smoke and its effects on the location, route, and speed of absorption in the body and on the sensory perception effects of the inhaled smoke."	( Brand differences of free-base nicotine delivery in cigarette smoke: the view of the tobacco industry documents. Connolly, GN; Ferris Wayne, G; Henningfield, JE, 2006)	0.87
" Associative tolerance to nicotine's analgesic effects was defined as a shift to the right of the dose-response curve (DRC) of rats in the explicitly paired condition with respect to the DRC of rats in the explicitly unpaired condition."	( Interdose interval effects on the development of contextual tolerance to nicotine's analgesic effects in rats (Rattus norvegicus). Cepeda-Benito, A; Davis, KW; Harraid, JH; Mendez, IA; Reynoso, JT; Susabda, A, 2006)	0.87
" Both nicotine and the nicotinic alpha-7 selective agonist AR-17779 significantly increased cell proliferation albeit with bell-shaped dose-response kinetics."	( Nicotine regulates SH-SY5Y neuroblastoma cell proliferation through the release of brain-derived neurotrophic factor. Carney, SL; Serres, F, 2006)	2.26
" In conclusion, when given prolonged access to the drug, both female and male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range and FR constraints previously observed in adult Lewis rats."	( Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug. Chen, H; Matta, SG; Sharp, BM, 2007)	0.9
"The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis."	( Guidelines on nicotine dose selection for in vivo research. Balfour, DJ; Benowitz, NL; Boyd, RT; Buccafusco, JJ; Caggiula, AR; Collins, AC; Craig, CR; Damaj, MI; Donny, EC; Gardiner, PS; Grady, SR; Heberlein, U; Leonard, SS; Levin, ED; Lukas, RJ; Markou, A; Marks, MJ; Matta, SG; McCallum, SE; Parameswaran, N; Perkins, KA; Picciotto, MR; Quik, M; Rose, JE; Rothenfluh, A; Schafer, WR; Stolerman, IP; Tyndale, RF; Wehner, JM; Zirger, JM, 2007)	0.7
" Dose-response data yield an EC(50) value for ACh of 19 microm."	( Neonicotinoid insecticides display partial and super agonist actions on native insect nicotinic acetylcholine receptors. Brown, LA; Buckingham, SD; Ihara, M; Matsuda, K; Sattelle, DB, 2006)	0.33
"In all countries, air nicotine concentrations increased with increasing questionnaire reported smoking in a dose-response fashion."	( Comparison of parental reports of smoking and residential air nicotine concentrations in children. Bellander, T; Brunekreef, B; Gehring, U; Giovannangelo, ME; Heinrich, J; Hoek, G; Leaderer, BP; Merkel, G; Nordling, E; Oldenwening, M, 2006)	0.89
" Dose-response curves for fchi increases evoked by intra-stream boluses of acetylcholine, nicotine and ATP were studied."	( Effects of combined cholinergic-purinergic block upon cat carotid body chemoreceptors in vitro. Fernández, R; Larraín, C; Reyes, EP; Zapata, P, 2007)	0.56
" An intermittent nicotine dosing regimen designed to resemble nicotine intake in a smoker was administered from GD1-20."	( Vaccination against nicotine does not prevent nicotine-induced changes in fetal nicotinic receptor binding and c-fos mRNA expression in rats. Chen, Y; Dufek, MB; Keyler, DE; Le, C; LeSage, MG; Leslie, FM; Pentel, PR, )	0.79
" There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects."	( A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder. Baker, A; Carr, VJ; Haile, M; Jansons, S; Lewin, TJ; Richmond, R; Taylor, RL; Wilhelm, K, 2006)	0.33
" One CAT was performed after a nicotine (NIC) dosing using a 21-mg transdermal patch, whereas the other CAT was performed after a placebo (PL) treatment."	( The effects of nicotine on the metabolic and hormonal responses during acute cold exposure. Blegen, M; Caine-Bish, N; Cheatham, CC; Glickman, EL; Kalinski, M; Kamimori, GH; Marcinkiewicz, JL; Otterstetter, R; Potkanowicz, ES, 2006)	0.97
" For rats with access to VS (VS-Only), nicotine (NIC-Only), both reinforcers contingent upon one response (NIC+VS) or both reinforcers contingent upon separate responses (2-Lever), unit dose-response relationships (0, 30, 60, or 90 microg/kg/infusion, free base) were determined over a 22-day acquisition period."	( The role of nicotinic acetylcholine receptors in the primary reinforcing and reinforcement-enhancing effects of nicotine. Caggiula, AR; Donny, EC; Liu, X; Palmatier, MI; Sved, AF, 2007)	0.82
" Dose-proportional increases in maximum observed plasma concentrations and area under the plasma concentration-time curve from time zero to the end of the dosing interval values were observed between the 1-mg and 2-mg daily doses of varenicline."	( Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy smokers. Burstein, AH; Clark, DJ; Faessel, HM; Gibbs, MA; Rohrbacher, K; Stolar, M, 2006)	0.33
"We provide novel pharmacokinetic and metabolic data on nicotine after systemic dosing in relation to common CYP2A6 genotypes."	( CYP2A6 genotype and the metabolism and disposition kinetics of nicotine. Benowitz, NL; Jacob, P; Lessov-Schlaggar, CN; Swan, GE; Tyndale, RF, 2006)	0.82
" nicotine dosing protocol that approximates the pattern of nicotine exposure in moderate to heavy smokers."	( Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats. Dufek, MB; Gustaf, E; LeSage, MG; Pentel, PR, 2006)	1.53
" Cigarette smoking increased heart rate and decreased skin temperature, but the nicotine dose-response curve flattened at higher doses, with a maximal response being observed in cigarettes at a nicotine content level of about 8 mg."	( Nicotine intake and dose response when smoking reduced-nicotine content cigarettes. Benowitz, NL; Herrera, B; Jacob, P, 2006)	2
" We examined the effect of chronic nicotine exposure on gene expression profiles during adolescence in female rats, who were dosed with nicotine (and control animals were dosed with saline) via subcutaneously implanted osmotic minipumps."	( Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain. Eppolito, AK; Fryxell, KJ; Ker, KF; Locklear, LL; McDonald, CG; Merchant, AD; Polesskaya, OO; Smith, LN; Smith, RF; Wheeler, TL, )	1.85
" Weekly dosing produced tolerance to nicotine's decreasing effects on vertical activity and increases (i."	( Sensitization and tolerance with episodic (weekly) nicotine on motor activity in rats. Farmer, JD; Jarema, KA; MacPhail, RC, )	0.66
" Dosing with the 21 mg/day nicotine patch was associated with mean "under-replacement" (53."	( Nicotine percentage replacement among smokeless tobacco users with nicotine patch. Dale, LC; Ebbert, JO; Hurt, RD; Moyer, TP; Post, JA; Schroeder, DR, 2007)	2.08
" Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms."	( Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: results from a pilot study with African American men. Augustson, EM; Benowitz, NL; Mabry, PL; Malcolm, RJ; Moser, RP; Tooze, JA, 2007)	2.08
" The most important findings in this study were that (1) moderate doses of nicotine accelerated the onset and increased blood pressure in SHR but not in WKY rats, (2) the nicotine dosage and time of treatment employed did not affect body weight, (3) chronic nicotine treatment differentially affected glutamatergic system in normotensive and hypertensive rats, and (4) spontaneously hypertensive rats seem to be more sensitive to peripherally administered nicotine than Wistar Kyoto rats considering blood pressure and glutamatergic neurotransmission changes."	( Chronic nicotine administration. Analysis of the development of hypertension and glutamatergic neurotransmission. Ferrari, MF; Fior-Chadi, DR, 2007)	1
" In the drug discrimination procedure, Ro-60-0175 was not generalised with nicotine but shifted the nicotine dose-response curve to the right in a dose-related manner."	( The serotonin 2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination. Naylor, CG; Quarta, D; Stolerman, IP, 2007)	0.81
"The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, and place in therapy of varenicline are reviewed."	( Varenicline: the newest agent for smoking cessation. Garwood, CL; Potts, LA, 2007)	0.34
"25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0."	( Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats. Filip, M; McCreary, AC; Przegaliński, E; Zaniewska, M, 2007)	0.8
" Patients kept daily diaries and recorded pain scores and self hydrocodone dosing upon awakening, in the afternoon, and at bed time."	( Effect of cigarette smoking on serum hydrocodone levels in chronic pain patients. Ackerman, WE; Ahmad, M, 2007)	0.34
"Nicotine, at the dosage levels smokers seek, is a relatively innocuous drug commonly delivered by a highly harmful device, cigarette smoke."	( Tobacco harm reduction: how rational public policy could transform a pandemic. Alcabes, P; Drucker, E; Sweanor, D, 2007)	1.78
" Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations."	( Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Checkoway, H; Factor, SA; Griffith, A; Higgins, DS; Kay, DM; Leis, B; Martinez, ED; Montimurro, JS; Nutt, JG; Payami, H; Powers, KM; Roberts, JW; Samii, A; Zabetian, CP, 2008)	0.35
" Topiramate (1-60 mg/kg, intraperitoneal) did not produce any nicotine-like or cocaine-like discriminative effects by itself and did not produce any shift in the dose-response curves for nicotine or cocaine discrimination."	( Topiramate does not alter nicotine or cocaine discrimination in rats. Barnes, C; Goldberg, SR; Justinova, Z; Le Foll, B; Wertheim, CE, 2008)	0.89
" The dose-response relationship was steeper among children."	( Secondhand smoke exposure among women and children: evidence from 31 countries. Avila-Tang, E; Breysse, P; Kim, S; Navas-Acien, A; Onicescu, G; Samet, JM; Wipfli, H; Yuan, J, 2008)	0.35
"Our study identified a positive and dose-response relationship between cigarette smoking and risk of stroke."	( Cigarette smoking and risk of stroke in the chinese adult population. Chen, CS; Chen, J; Chen, JC; Duan, X; Gu, D; He, J; Huang, JF; Kelly, TN; Wu, X, 2008)	0.35
"Participants engaged in four sessions: the first three to assess dose-response effects of nasal spray nicotine (0, 5, 10 microg/kg) on reward, as well as mood, physiological, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure."	( Initial nicotine sensitivity in humans as a function of impulsivity. Coddington, SB; Jetton, C; Karelitz, JL; Lerman, C; Perkins, KA; Scott, JA; Wilson, AS, 2008)	1
" Our previous work had shown that intermittent nicotine dosing reduced L-DOPA-induced dyskinetic-like movements in nonhuman primates."	( Continuous and intermittent nicotine treatment reduces L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias in a rat model of Parkinson's disease. Bordia, T; Campos, C; Huang, L; Quik, M, 2008)	0.9
"This study examines the possibility that company-specific and brand-specific strategies of the major moist snuff manufacturers involve controlling free nicotine content and ease of dosing with products that are designed and targeted to specific groups."	( Free nicotine content and strategic marketing of moist snuff tobacco products in the United States: 2000-2006. Alpert, HR; Connolly, GN; Koh, H, 2008)	1.06
" Lower doses of baclofen also did not reduce discriminative stimulus effects of the training dose of nicotine and did not significantly shift the dose-response curve for nicotine discrimination."	( Effects of baclofen on conditioned rewarding and discriminative stimulus effects of nicotine in rats. Goldberg, SR; Le Foll, B; Wertheim, CE, 2008)	0.79
"Caffeine, CPT, and MSX-3 partially generalized to nicotine and shifted nicotine dose-response curves leftwards."	( Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats. Barnes, C; Ferré, S; Goldberg, SR; Justinova, Z; Le Foll, B; Pappas, LA; Wertheim, CE, 2009)	0.82
"Although cigarette smoking is known to be a risk factor for ischemic stroke, there are few data on the dose-response relationship between smoking and stroke risk in a young ethnically diverse population."	( Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Bhat, VM; Cole, JW; Giles, WH; Kittner, SJ; Malarcher, AM; Sorkin, JD; Stern, BJ; Wozniak, MA, 2008)	0.35
"These results suggest a strong dose-response relationship between cigarette smoking and ischemic stroke risk in young women and reinforce the need for aggressive smoking cessation efforts in young adults."	( Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Bhat, VM; Cole, JW; Giles, WH; Kittner, SJ; Malarcher, AM; Sorkin, JD; Stern, BJ; Wozniak, MA, 2008)	0.35
" Participants engaged in 4 sessions, the first 3 to assess the dose-response effects of nasal spray nicotine (0, 5, 10 microg/kg) on rewarding, mood, physiological, sensory processing, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure."	( Variability in initial nicotine sensitivity due to sex, history of other drug use, and parental smoking. Coddington, SB; Jetton, C; Karelitz, JL; Lerman, C; Perkins, KA; Scott, JA; Wilson, AS, 2009)	0.88
" This article reviews NRT, bupropion, and varenicline pharmacokinetics and dosing literature for patients with CKD."	( Smoking cessation therapy considerations for patients with chronic kidney disease. Manley, HJ; Stack, NM, )	0.13
"The objective of the study was to evaluate the response of nicotine self-administration (NSA) to pharmacological agents related to the smoking cessation medication bupropion and to nicotine dosing mimicking nicotine replacement on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement."	( Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement. Adamson, KL; Coen, KM; Corrigall, WA, 2009)	0.85
" The effect of nicotine replacement was examined on the PR schedule by chronic dosing with osmotic minipumps."	( Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement. Adamson, KL; Coen, KM; Corrigall, WA, 2009)	0.96
" Chronic nicotine dosing reduced self-administration."	( Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement. Adamson, KL; Coen, KM; Corrigall, WA, 2009)	1.02
" The dose-response effect of nicotine then was compared with the effects of increased reinforcer magnitude on responding."	( Differential-reinforcement-of-low-rate-schedule performance and nicotine administration: a systematic investigation of dose, dose-regimen, and schedule requirement. Brown, SJ; Doughty, AH; Hughes, DM; Kirshenbaum, AP, 2008)	0.88
" In this study, dosing of transgenic mice (J20 strain) with mutated human APP (Swedish mutations: K670N and M671L and Indiana mutation: V717F) transgene, with nicotine in drinking water for 20 weeks did not have a significant effect on total levels of Abeta 40 or 42 in hippocampus or cortex."	( Absence of effect of chronic nicotine administration on amyloid beta peptide levels in transgenic mice overexpressing mutated human APP (Sw, Ind). Anand, K; Lue, LF; Reid, RT; Sabbagh, MN; Stadnick, T; Walker, DG, 2008)	0.83
" The present study was undertaken to explore the dose-response effects of PBDE 209 on spontaneous behaviour, habituation and its effects on the murine cholinergic system."	( Neonatal exposure to deca-brominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice. Eriksson, P; Fredriksson, A; Johansson, N; Viberg, H, 2008)	0.35
" Microarray analysis revealed that, independent of the dose of NNK, expression of 30 genes was significantly altered; 22 of these genes showed a dose-response pattern."	( Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. El-Bayoumy, K; Freeman, WM; Prokopczyk, B; Sinha, I; Trushin, N, 2009)	0.58
" A review of internal documents indicates important historical differences, as well as significant differences between commercial brands, underscoring the effectiveness of methods adopted by manufacturers to control nicotine dosing and target the needs of specific populations of smokers through commercial product development."	( Tobacco industry manipulation of nicotine dosing. Carpenter, CM; Wayne, GF, 2009)	0.82
" The quality and the certainty of the nicotine replacement therapy will be enhanced by reflecting considerations concerning the indication, correlation of single NRT form to the appropriate user as well as the right dosage and compliance matters."	( [Smoking cessation with nicotine replacement therapy (NRT) - a scientific update]. Groman, E; Homeier, I; Lichtenschopf, A; Mulzer, KH, 2009)	0.93
" Neonatal exposure to decabrominated diphenyl ether (PBDE 209) causes dose-response changes in spontaneous behaviour and cholinergic susceptibility in adult mice."	( Neurodevelopmental effects of decabromodiphenyl ether (BDE-209) and implications for the reference dose. Goodman, JE, 2009)	0.35
" HF-1 at the stationary phase was enhanced with increasing nicotine concentration, showing a striking dose-response relationship."	( Antioxidant enzyme activity in bacterial resistance to nicotine toxicity by reactive oxygen species. Lü, Z; Min, H; Shao, T; Yan, B; Yuan, H, 2009)	0.84
"Flexibly dosed triple-combination pharmacotherapy for up to 6 months was more effective than standard-duration nicotine patch therapy for outpatient smokers with medical illnesses."	( Triple-combination pharmacotherapy for medically ill smokers: a randomized trial. Bover, MT; Carson, JL; Foulds, J; Greenhaus, S; Hoover, DR; Schmelzer, AC; Steinberg, MB, 2009)	0.56
" We then assessed the spontaneous acquisition of intravenous self-administration with nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule and a single within-session ascending dose-response test."	( The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats. Cador, M; Caillé, S; Clemens, KJ; Stinus, L, 2009)	0.82
"All patients improved motor scores at 3 months (-65 +/- 22% 'off', -89 +/- 12% 'on') and most received fewer dopaminergic drugs (-30% dosage in average)."	( Dopamine transporter imaging under high-dose transdermal nicotine therapy in Parkinson's disease: an observational study. Brugières, P; Capacchione, D; Cesaro, P; Itti, E; Itti, L; Maison, P; Malek, Z; Meignan, M; Villafane, G, 2009)	0.6
" Both groups self-administered more than the daily recommended dosage of 8 uses."	( Use of nicotine substitute prescribed at hourly plus ab libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial. Bodenmann, P; Rey, L; Secretan, F; Vaucher, P; Zellweger, JP, 2009)	0.81
"We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr."	( Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure. Benowitz, NL; Dains, KM; Dempsey, D; Herrera, B; Jacob, P; Yu, L, 2009)	1.07
"Further exploration in larger samples, using more stringent selection criteria, a wider range of measures, and a less aversive dosing method, may provide a full test of the possible utility of the parental history model for illuminating biobehavioral mechanisms underlying response to nicotine."	( Substance use, trait measures, and subjective response to nicotine in never-smokers stratified on parental smoking history and sex. Finkenauer, R; Langenecker, SA; Mehringer, AM; Pomerleau, CS; Pomerleau, OF; Sirevaag, EJ; Snedecor, SM, 2009)	0.77
" Furthermore, adding nicotine to cocaine shifted the cocaine dose-response function to the left in four of the five monkeys."	( Self-administration of cocaine and nicotine mixtures by rhesus monkeys. Freeman, KB; Woolverton, WL, 2009)	0.95
" In dose-response studies, several compounds showed strong inhibitory activities with IC50 values at nanomolar or low nanomolar concentrations."	( Derivatives of (phenylsulfonamido-methyl)nicotine and (phenylsulfonamido-methyl)thiazole as novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: synthesis and biological activities in vitro. Chen, JH; Du, LL; Leng, Y; Shen, JH; Shen, Y; Zhang, X; Zhou, Y, 2009)	0.62
" In a series of experiments, the dose-response curve was obtained, pairings between the drug and initially non-preferred versus preferred compartments were compared, and the involvement of mGluR5 receptors in nicotine-induced CPP was evaluated."	( Nicotine-induced conditioned place preference in rats: sex differences and the role of mGluR5 receptors. Kanit, L; Keser, A; Pogun, S; Yararbas, G, 2010)	1.99
" Subjects randomized to active treatment followed a double-blind step-down dosing regimen: 24-h/21-mg patches for the first 6 weeks of treatment, followed by 14- and 7-mg patches for successive 2-week periods."	( Prediction of abstinence at 10 weeks based on smoking status at 2 weeks during a quit attempt: secondary analysis of two parallel, 10-week, randomized, double-blind, placebo-controlled clinical trials of 21-mg nicotine patch in adult smokers. Ferguson, SG; Gitchell, JG; Sembower, MA; Shiffman, S, 2009)	0.54
" Finally, performance of all animals was tracked for 8 days after the end of all dosing with nicotine."	( The duration of nicotine-induced attentional enhancement in the five-choice serial reaction time task: lack of long-lasting cognitive improvement. Mesdaghinia, A; Morris, HV; Naylor, CG; Stolerman, IP, 2009)	0.92
" Metabolizing enzyme to produce cotinine from nicotine was saturated after multiple oral dosing for 4 weeks in a low dose (1 mg/kg/day), but within 1 week in the dose of 5 and 10 mg/kg/day."	( Relations between toxicity and altered tissue distribution and urinary excretion of nicotine, cotinine, and hydroxycotinine after chronic oral administration of nicotine in rats. Chung, BC; Hong, J; Jung, BH; Kim, KY; Lee, YJ, 2010)	0.84
" However, prazosin did not have nicotine-like discriminative effects and did not alter the dose-response curve for nicotine discrimination."	( Noradrenergic alpha1 receptors as a novel target for the treatment of nicotine addiction. Forget, B; Goldberg, SR; Le Foll, B; Mascia, P; Pushparaj, A; Wertheim, C, 2010)	0.88
"Internal EEG research was used to determine dose-response relations and effective threshold levels for nicotine, emphasising the importance of form and mechanism of nicotine delivery for initiating robust central nervous system (CNS) effects."	( Human electroencephalography and the tobacco industry: a review of internal documents. Connolly, GN; Panzano, VC; Pickworth, WB; Wayne, GF, 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)	0.82
" A dose-response test was then conducted, followed by extinction and cue- and nicotine-induced reinstatement."	( The effects of response operandum and prior food training on intravenous nicotine self-administration in rats. Cador, M; Caillé, S; Clemens, KJ, 2010)	0.82
"The use of the NP operandum resulted in markedly higher levels of IVSA across acquisition and across dose-response testing compared with the LVR group."	( The effects of response operandum and prior food training on intravenous nicotine self-administration in rats. Cador, M; Caillé, S; Clemens, KJ, 2010)	0.59
" We evaluated the dose-response effects of nicotine on locomotor activity, song production, food intake and body weight."	( In vivo nicotine exposure in the zebra finch: a promising innovative animal model to use in neurodegenerative disorders related research. Cappendijk, SL; Chalise, P; Halquist, MS; James, JR; Miller, GL; Pirvan, DF; Rodriguez, MI, 2010)	1.06
" The aim of this study was to assess an alternative oral dosing method that could reduce the distress and morbidity associated with standard gavage techniques."	( Alternative method of oral dosing for rats. Atcha, Z; Aw, CC; Browne, ER; Goh, CW; Lim, JS; Neo, AH; Pemberton, DJ; Rourke, C, 2010)	0.36
" The decreased efficiency of aerosol production during e-cigarette smoking makes dosing nonuniform over time and calls into question their usefulness as nicotine delivery devices."	( Conventional and electronic cigarettes (e-cigarettes) have different smoking characteristics. Talbot, P; Trtchounian, A; Williams, M, 2010)	0.56
"Acquisition, dose-response function, extinction, and cue-induced reinstatement of operant behavior were characterized."	( Patterns of responding differentiate intravenous nicotine self-administration from responding for a visual stimulus in C57BL/6J mice. Contet, C; Jarrell, H; Kenny, PJ; Markou, A; Whisler, KN, 2010)	0.62
" Additionally, post-nicotine episodes showed a different dose-response curve than the pre-nicotine episodes: post-nicotine wheel turns increased as the dose decreased, whereas pre-nicotine wheel turns remained relatively constant as the dose changed."	( Effects of multiple daily nicotine administrations on pre- and post-nicotine circadian activity episodes in rats. Gillman, AG; Kosobud, AE; Timberlake, W, 2010)	0.98
" In the multiple cytotoxicity endpoint (MCE) assay with TK-6 cells, the cigarette varieties that had the highest EC50s for reduced cell growth also showed a positive dose-response relationship for necrotic cells."	( Cytotoxicity of eight cigarette smoke condensates in three test systems: comparisons between assays and condensates. Li, AP; Polzin, G; Richter, PA; Roy, SK, 2010)	0.36
"The prevalence of lost autonomy was 40% among subjects who smoked 1 or 2 days/month and 41% among subjects who averaged less than one cigarette/day and increased in a dose-response pattern."	( Children's loss of autonomy over smoking: the Global Youth Tobacco Survey. DiFranza, JR; Soteriades, ES; Spanoudis, G; Talias, MA; Warren, CW, 2011)	0.37
" These findings indicate that a low, daily dosing of IV prenatal nicotine produces long-lasting alterations in auditory PPI."	( Prenatal IV nicotine exposure produces a sex difference in sensorimotor gating of the auditory startle reflex in adult rats. Harrod, SB; Lacy, RT; Mactutus, CF, 2011)	0.99
" Premature discontinuation and insufficient dosing have been offered as possible explanations."	( Adherence to and reasons for premature discontinuation from stop-smoking medications: data from the ITC Four-Country Survey. Balmford, J; Borland, R; Cummings, KM; Hammond, D, 2011)	0.37
" Mecamylamine (1mg/kg) produced parallel rightward shifts in the dose-response curves for nicotine (3."	( The effects of nicotine, varenicline, and cytisine on schedule-controlled responding in mice: differences in α4β2 nicotinic receptor activation. Cunningham, CS; McMahon, LR, 2011)	0.94
" 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)	0.82
" The results reveal dose-dependent effects of nicotine during adolescence with apparent sensitization at different ends of the dosage spectrum examined compared to adults."	( Age-dependent effects of initial exposure to nicotine on serotonin neurons. Bang, SJ; Commons, KG, 2011)	0.89
"A 23-year old woman with BPD presented in our clinic with a 4-month history of intravenous application of a liquid dosage form of nicotine that is generally used for nasal application."	( Non-suicidal self-injury by intravenous application of nicotine in a patient with borderline personality disorder resulting in substance dependence. Freudenmann, R; Gahr, M; Schönfeldt-Lecuona, C, 2011)	0.82
" nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation."	( Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats. Harris, AC; Keyler, DE; Lesage, MG; Mattson, CK; Pentel, PR; Pettersson, S; Pravetoni, M; Raleigh, MD, 2011)	1.6
"3 mg/kg) not previously tested on attention improved response accuracy, resulting in an inverted U-shape dose-response function."	( Selective nicotinic receptor antagonists: effects on attention and nicotine-induced attentional enhancement. Hahn, B; Shoaib, M; Stolerman, IP, 2011)	0.61
"A series of studies was designed to assess the acute dose-response effects of nicotine and the nicotinic receptor antagonist mecamylamine alone, and in combination with nicotine, on impulsive choice and behavioural disinhibition in rats."	( Acute nicotine increases both impulsive choice and behavioural disinhibition in rats. Harrison, AA; Kolokotroni, KZ; Rodgers, RJ, 2011)	1.08
" Repeated doses of varenicline have thus the opposite effect of repeated nicotine dosing at 24h intervals, previously shown to produce sensitization of brain activation under the same experimental conditions."	( A comparison of brain and behavioral effects of varenicline and nicotine in rats. Bircher, R; Chen, W; DiFranza, JR; Heffernan, M; Huang, W; King, J; Rane, P; Shields, J, 2011)	0.84
"The dose-response between CPD and nicotine equivalents, and NNAL and PAH was flat for Black but positive for White smokers (Race × CPD interaction, all ps < ."	( Racial differences in the relationship between number of cigarettes smoked and nicotine and carcinogen exposure. Benowitz, NL; Dains, KM; Dempsey, D; Jacob, P; Wilson, M, 2011)	0.88
" The evidence indicates that nicotine can have dual effects on the speed of locomotion, which is dependent on differences in its dosage and treatment time."	( Concentration- and time-dependent behavioral changes in Caenorhabditis elegans after exposure to nicotine. Kowalski, M; Lesicki, A; Sobkowiak, R, 2011)	0.88
"4 mg kg(-1) per infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-s (FR5TO20) reinforcement schedule and consumed the drug according to an inverted 'U'-shaped dose-response curve."	( Intravenous nicotine self-administration and cue-induced reinstatement in mice: effects of nicotine dose, rate of drug infusion and prior instrumental training. Fowler, CD; Kenny, PJ, 2011)	0.75
"The study had evaluated the dose-response curves for nicotine and KA and for KA in nicotine-pretreated mice and for topiramate against KA-induced seizures."	( Nicotine reversal of anticonvulsant action of topiramate in kainic acid-induced seizure model in mice. Chakrabarti, A; Hota, D; Sahai, AK; Sood, N, 2011)	2.06
" Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 ± 13 and 66 ± 7% of naive at 4 h post last CPF dosing, respectively)."	( Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition. Gunawan, R; Hjerpe, AL; Lee, S; Poet, TS; Smith, JN; Timchalk, C, 2011)	0.97
" This analytical method provides support for preclinical NIC pharmacokinetic and toxicological studies after controlled dosing protocols."	( Simultaneous quantification of nicotine and metabolites in rat brain by liquid chromatography-tandem mass spectrometry. Fleckenstein, AE; Miller, EI; Nielsen, SM; Vieira-Brock, PL; Wilkins, DG, 2011)	0.66
" The present study indicates that a single exposure to Bisphenol A on postnatal day 10 can alter adult spontaneous behavior and cognitive function in mice, effects that are both dose-response related and long-lasting/irreversible."	( Dose-dependent behavioral disturbances after a single neonatal Bisphenol A dose. Buratovic, S; Eriksson, P; Fredriksson, A; Viberg, H, 2011)	0.37
" There is still no agreement on the daily dosage of nicotine or the method of administration."	( Can nicotine be used medicinally in Parkinson's disease? Cesaro, P; Fenelon, G; Grapin, F; Remy, P; Thiriez, C; Villafane, G, 2011)	1.18
" In the nicotine group, a dose-response curve was measured after the nose-poke behavior stabilized."	( Nicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction. Gamaleddin, I; Le Foll, B; Picciotto, MR; Pushparaj, A; Roder, J; Steiner, RC; Yan, Y, 2012)	2.26
"This research describes the development and validation of a biorelevant in vitro release/permeation system to predict the in vivo performance of oral transmucosal dosage forms."	( A biorelevant in vitro release/permeation system for oral transmucosal dosage forms. Barr, WH; Delvadia, PR; Karnes, HT, 2012)	0.38
" In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies."	( In vivo predictive release methods for medicated chewing gums. Gajendran, J; Kraemer, J; Langguth, P, 2012)	0.38
" One mechanism may be extinction, but the duration of the current dosing protocol may not be sufficient."	( Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers. Ashare, RL; Blair, IA; Leone, F; Mesaros, AC; Strasser, AA; Tang, KZ, 2012)	0.38
"Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months."	( Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke. Cheng, L; Gao, SG; Jiang, W; Lei, GH; Li, KH; Liu, WH; Sun, JP; Tian, J; Wei, LC; Xiao, WF; Xie, Q; Xiong, YL; Xu, M; Zeng, C; Zhang, FJ, 2012)	0.38
" Two different nicotine replacement therapy dosing regiments were administered according to the baseline salivary cotinine level."	( A randomized clinical trial of trans-dermal nicotine replacement in pregnant African-American smokers. El-Mohandes, AA; Gantz, MG; Kiely, M; Perry, DC; Tan, S; Windsor, R, 2013)	1
"2 mg/kg) in combination with METH induced reinstatement, suggesting that NIC produced a leftward shift in the dose-response effect of METH to reinstate CPP."	( Reinstatement of methamphetamine conditioned place preference in nicotine-sensitized rats. Bardo, MT; Berry, JN; Neugebauer, NM, 2012)	0.62
" In addition, acute NAC administration showed a nonsignificant trend in attenuating nicotine self-administration under a progressive-ratio schedule that was similar to the dose-response function under the fixed-ratio schedule."	( N-acetylcysteine decreased nicotine self-administration and cue-induced reinstatement of nicotine seeking in rats: comparison with the effects of N-acetylcysteine on food responding and food seeking. D'Souza, MS; Markou, A; Ramirez-Niño, AM, 2013)	0.91
" Like cytisine and nicotine, CC4-induced conditioned place preference (CPP), and its self-administration shows an inverted-U dose-response curve."	( CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking cessation. Braida, D; Clementi, F; Fasoli, F; Fucile, S; Gotti, C; Grady, SR; Loi, B; Manfredi, I; Marks, MJ; Pucci, L; Sala, M; Sparatore, F; Tasso, B; Wageman, CR; Zoli, M, 2013)	0.72
"0 mg/kg/infusion) and a dose-response curve was generated (0."	( Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self-administration during adulthood in male C57BL/6J mice. Blaha, CD; Dickson, PE; Miller, MM; Mittleman, G; Rogers, TD, 2014)	0.72
" dosing of ABT-107 (0."	( Effects of the novel α7 nicotinic acetylcholine receptor agonist ABT-107 on sensory gating in DBA/2 mice: pharmacodynamic characterization. Bitner, RS; Gopalakrishnan, M; Radek, RJ; Robb, HM; Stevens, KE, 2012)	0.38
" Refill solutions were tested on human embryonic stem cells (hESC), mouse neural stem cells (mNSC), and human pulmonary fibroblasts (hPF) using the MTT assay, and NOAELs and IC(50)s were determined from dose-response curves."	( Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Bahl, V; Davis, B; Lin, S; Talbot, P; Wang, YH; Xu, N, 2012)	0.38
" Nicotine has analgesic properties and it is hypothesized that cigarette smoking might decrease the dosage of hydrocodone needed for the relief of chronic pain."	( The effect of cigarette smoking on hydrocodone efficacy in chronic pain patients. Ackerman, WE, 2012)	1.29
" Contrary to expectations derived from the self-medication hypothesis, nicotine showed no significant effects on the dependent variables, perhaps because of the dosage used and the delay between the administration of nicotine and the performance of the role-play."	( Effects of nicotine on social cognition, social competence and self-reported stress in schizophrenia patients and healthy controls. Brinkmeyer, J; Drusch, K; Fisahn, K; Lowe, A; Mobascher, A; Musso, F; Ohmann, C; Shah, J; Warbrick, T; Winterer, G; Wölwer, W, 2013)	1.01
" The goal of this study was to determine whether cigarettes that vary in nicotine content produce an expected dose-response effect."	( Dose-response effects of spectrum research cigarettes. Denlinger, RL; Donny, E; Hatsukami, DK; Heishman, SJ; Jensen, J; Mackowick, KM; Murphy, SE; Roper-Batker, AN; Thomas, BF; Vogel, RI, 2013)	0.62
"In the first study, significant dose-response effects were observed, particularly between the LN and HN cigarettes."	( Dose-response effects of spectrum research cigarettes. Denlinger, RL; Donny, E; Hatsukami, DK; Heishman, SJ; Jensen, J; Mackowick, KM; Murphy, SE; Roper-Batker, AN; Thomas, BF; Vogel, RI, 2013)	0.39
" In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters."	( 3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors. Camarasa, J; Escubedo, E; Garcia-Ratés, S; Pubill, D, 2013)	0.59
" The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose-response related and long-lasting/irreversible."	( Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose. Eriksson, P; Lee, I; Viberg, H, 2013)	0.39
"92), and we found clear evidence of an inverse dose-response correlation between cumulative dose of snuff use and the risk of developing the disease."	( Nicotine might have a protective effect in the etiology of multiple sclerosis. Alfredsson, L; Hedström, AK; Hillert, J; Olsson, T, 2013)	1.83
" The doses identified as best doses from two nicotine dose-response curve determinations were unrelated, and the improvement associated with the best dose observed during the first dose-response curve determination was not reliable when the dose was administered repeatedly."	( A critical examination of best dose analysis for determining cognitive-enhancing potential of drugs: studies with rhesus monkeys and computer simulations. Ator, NA; Dallery, J; Katz, BR; Soto, PL, 2013)	0.65
"0305) in a dose-response fashion with low (OR = 1."	( Associations of prenatal nicotine exposure and the dopamine related genes ANKK1 and DRD2 to verbal language. Cho, K; Eicher, JD; Gruen, JR; Miller, LL; Mueller, KL; Powers, NR; Ring, SM; Tomblin, JB, 2013)	0.69
" We also present a receptor blocking study in a nicotine subject dosed with the α4β2-nAChR-selective partial agonist varenicline."	( PET imaging of high-affinity α4β2 nicotinic acetylcholine receptors in humans with 18F-AZAN, a radioligand with optimal brain kinetics. Brasic, JR; Chamroonrat, W; Dannals, RF; Gao, Y; Gean, EG; Horti, AG; Kim, J; Kuwabara, H; Mathur, A; McCaul, ME; Valentine, H; Wand, G; Willis, W; Wong, DF, 2013)	0.65
"Perinatal HFD compared to chow exposure increased nicotine-self administration behavior during fixed ratio and dose-response testing and caused an increase in breakpoint using progressive ratio testing, while nicotine seeking in response to nicotine prime-induced reinstatement was reduced."	( Stimulation of nicotine reward and central cholinergic activity in Sprague-Dawley rats exposed perinatally to a fat-rich diet. Guo, WR; Karatayev, O; Leibowitz, SF; Lukatskaya, O; Moon, SH; Morganstern, I; Shaji, J, 2013)	1
" Additionally, methoxsalen potentiated nicotine-induced antinociception and hypothermia as evidenced by leftward shifts in nicotine's dose-response curve."	( Pharmacokinetic and pharmacodynamics studies of nicotine after oral administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor. Alsharari, SD; Damaj, MI; Siu, EC; Tyndale, RF, 2014)	0.93
" After a washout period, repeat TC-8831 dosing led to a greater decline in LIDs (60%) in both sets of monkeys that was similar to the effect of nicotine."	( Nicotinic receptor agonists reduce L-DOPA-induced dyskinesias in a monkey model of Parkinson's disease. Bencherif, M; Carroll, FI; Letchworth, S; Mallela, A; Quik, M; Sohn, D; Zhang, D, 2013)	0.59
"During smoke-free psychiatric hospitalizations, clinical management of nicotine withdrawal may be enhanced by offering patients NRT directly on admission, educating patients on the benefits of NRT, and increasing the dosage for more dependent smokers."	( Clinical management of tobacco dependence in inpatient psychiatry: provider practices and patient utilization. Hall, SE; Hall, SM; Hickman, N; Kim, R; Leyro, TM; Prochaska, JJ, 2013)	0.62
" Dose-response relationships were very well described by the exponential demand function (r(2) values>0."	( Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy. Burroughs, D; Grebenstein, P; LeSage, MG; Zhang, Y, 2013)	0.72
"Low and high doses of NIC, cytisine (CYT), CC4 and CC26 respectively improved and worsened the mean running time, showing an inverted U dose-response function."	( Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish. Braida, D; Gotti, C; Martucci, R; Ponzoni, L; Sala, M; Sparatore, F, 2014)	0.4
" Nicotine dose-dependently increased the proportion of timed IRTs; the dose-response curve was shifted leftwards in SHR relative to WKY."	( Detrimental effects of acute nicotine on the response-withholding performance of spontaneously hypertensive and Wistar Kyoto rats. Mazur, GJ; Sanabria, F; Watterson, E; Wood-Isenberg, G, 2014)	1.6
" In addition 30/30 cynomolgus monkeys dosed with nicotine vaccine nanoparticles showed dose-dependent antibody generation and T cell recall response compared to saline injected controls."	( Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates. Altreuter, DH; Fraser, CC; Ilyinskii, P; Johnston, L; Keegan, M; Kishimoto, TK; LaMothe, RA; Pittet, L, 2014)	0.66
" This study examined dose-response relationships for murine α6β2*-nicotinic acetylcholine receptor (nAChR) down-regulation by chronic nicotine treatment."	( α6β2*-subtype nicotinic acetylcholine receptors are more sensitive than α4β2*-subtype receptors to regulation by chronic nicotine administration. Grady, SR; Marks, MJ; McIntosh, JM; Paley, MA; Salminen, O; Wageman, CR; Whiteaker, P, 2014)	0.81
" A dose-response relationship with adverse events occurred in most trials."	( High-dose transdermal nicotine replacement for tobacco cessation. Brokowski, L; Chen, J; Tanner, S, 2014)	0.72
" The progressive ratio schedule was then employed to determine the motivation to receive each drug and within-subject dose-response curves were also produced (7."	( Tobacco particulate matter self-administration in rats: differential effects of tobacco type. Brennan, KA; Crowther, A; Putt, F; Roper, V; Truman, P; Waterhouse, U, 2015)	0.42
"CC4 and CC26 induced CPP with an inverted U-shaped dose-response curve similar to that of NIC."	( The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine receptors. Andrea, D; Braida, D; Cannazza, G; Clementi, F; Fasoli, F; Gotti, C; Manfredi, I; Papke, RL; Ponzoni, L; Pucci, L; Sala, M; Stokes, C, 2014)	0.66
"The dose-response relationship between smoking and pulmonary function in women may have been significantly over-estimated by studies that employed a self-reporting questionnaire."	( Dose-related effect of urinary cotinine levels on pulmonary function among Korean women. Jang, TW; Kim, HR; Kim, KY; Koo, JW; Lee, HE; Myong, JP; Park, CY, 2014)	0.4
" Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures."	( Developmental consequences of fetal exposure to drugs: what we know and what we still must learn. Graham, DL; Money, KM; Ross, EJ; Stanwood, GD, 2015)	0.42
" We found that α6 KO mice exhibited a rightward shift in the nicotine dose-response curve compared with WT littermates but that α4 KO failed to show nicotine preference, suggesting that α6α4β2*-nAChRs are involved."	( Differential roles of α6β2* and α4β2* neuronal nicotinic receptors in nicotine- and cocaine-conditioned reward in mice. Bowers, MS; Brunzell, DH; Damaj, MI; Maldoon, PP; Marks, MJ; Maskos, U; McIntosh, JM; Sanjakdar, SS, 2015)	0.89
" In this study, we examined whether mice pretreated with chronic nicotine, at a dosing regimen that results in maximal nicotinic acetylcholine receptor (nAChR) upregulation, would display evidence of nicotine-dependent behaviour during nicotine self-administration."	( Chronic nicotine pretreatment is sufficient to upregulate α4* nicotinic receptors and increase oral nicotine self-administration in mice. Nashmi, R; Renda, A, 2014)	1.07
" Most have utilized peak doses along nicotine's dose-response curve (15 and 30μg/kg) that establish NSA in the majority of animals."	( Effect of food training and training dose on nicotine self-administration in rats. Garcia, KL; Lê, AD; Tyndale, RF, 2014)	0.94
" The behavioural defects were dose-response related and persistent."	( Developmental exposure to the polybrominated diphenyl ether PBDE 209: Neurobehavioural and neuroprotein analysis in adult male and female mice. Buratovic, S; Eriksson, P; Fredriksson, A; Viberg, H, 2014)	0.4
" This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality."	( Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator. Kamrath, P; Kreuz, J; Linhart, M; Lorenzen, H; Nickenig, G; Schwab, JO; Skowasch, D; Tiyerili, V, 2015)	0.42
" There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients."	( Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator. Kamrath, P; Kreuz, J; Linhart, M; Lorenzen, H; Nickenig, G; Schwab, JO; Skowasch, D; Tiyerili, V, 2015)	0.42
"3 mg/kg ABT-107 (doses were determined through initial dose-response experiments and prior studies) and were trained and tested for CFC."	( ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice. Connor, DA; Gould, TJ; Yildirim, E, 2015)	0.69
" We further explored the dose-response relationship of miR-124 and let-7a with two biomarkers of tobacco exposure and found that this relationship was affected by adjustments based on age, pack-year and gender."	( Quantification of plasma microRNAs in a group of healthy smokers, ex-smokers and non-smokers and correlation to biomarkers of tobacco exposure. Banerjee, A; Camacho, OM; Minet, E; Waters, D, 2015)	0.42
" To determine dose-response relationships, the association between smoking pack-years and cortical thickness was tested and then repeated, while controlling for a comprehensive list of covariates including, among others, cognitive ability before starting smoking."	( Cigarette smoking and thinning of the brain's cortex. Bastin, ME; Chouinard-Decorte, F; Corley, J; Deary, IJ; Ducharme, S; Karama, S; Starr, JM; Wardlaw, JM, 2015)	0.42
" Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose-response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration."	( Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse. Armirotti, A; Auber, A; Bandiera, T; Barnes, C; Bertorelli, R; Chefer, SI; Goldberg, SR; Justinova, Z; Mascia, P; Moreno-Sanz, G; Panlilio, LV; Piomelli, D; Redhi, GH; Secci, ME; Yasar, S, 2015)	0.83
" The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats."	( Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats. Boutros, N; Markou, A; Semenova, S, 2016)	0.97
" It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing."	( Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet. Abedi, S; Algava, D; Chen, D; Guo, WR; Karatayev, O; Leibowitz, SF; Lukatskaya, O; Moon, SH, 2015)	2.19
" For non-smokers, the wide variability of ECIGs on the market is especially troublesome: low nicotine products may lead them to initiate nicotine self-administration and progress to higher dosing ECIGs or other products, and those that deliver more nicotine may produce nicotine dependence where it was not otherwise present."	( Electronic cigarettes and nicotine dependence: evolving products, evolving problems. Cobb, CO; Eissenberg, T; Hendricks, PS, 2015)	0.94
" Such additives may enhance dependence by helping to optimise nicotine delivery and dosing and through cueing and learned behaviour."	( A study of pyrazines in cigarettes and how additives might be used to enhance tobacco addiction. Agaku, IT; Alpert, HR; Connolly, GN, 2016)	0.67
" Though oral nicotine may not be totally risk-free, continuing research on this mode of nicotine administration is worthwhile to determine optimal dosing and duration of consumption for its potential use as an NRT."	( Oral Nicotine Alters Uterine Histo-Morphology but Does Not Disrupt the Estrous Cycle in Female Rats. Halder, S; Pearce, AR; Trauth, S, 2016)	1.32
" Study I: A dose-response relationship (N = 20) between 0, 2, and 4 mg nicotine gum."	( Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study. Arendt Nielsen, T; Arendt-Nielsen, L; Boudreau, SA; Nielsen, BP; Wang, K, 2016)	0.91
"A dose-response elevation in heart rate was attenuated when nicotine was combined with menthol."	( Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study. Arendt Nielsen, T; Arendt-Nielsen, L; Boudreau, SA; Nielsen, BP; Wang, K, 2016)	0.92
" Furthermore, a significant inverse dose-response relationship was observed for the number of pack-years smoked."	( Association between cigarette smoking and Parkinson's disease: A meta-analysis. Li, W; Li, X; Liu, G; Shen, X; Tang, Y, )	0.13
" We found a trend of higher adjusted odds ratios with higher maternal HNC levels, suggesting a dose-response relationship between maternal smoke exposure and CHDs."	( Modification of the association between maternal smoke exposure and congenital heart defects by polymorphisms in glutathione S-transferase genes. Chen, X; Deng, K; Deng, Y; Li, J; Li, N; Li, S; Li, X; Lin, Y; Liu, Z; Mu, D; Tian, X; Wang, Y; Yang, J; Zhu, J, 2015)	0.42
" NIC abolished anodal tDCS-induced motor cortex excitability enhancement, which was restituted under medium dosage of DMO."	( Mechanisms of Nicotinic Modulation of Glutamatergic Neuroplasticity in Humans. Batsikadze, G; Fresnoza, S; Grundey, J; Kuo, MF; Lugon, MDMV; Nakamura-Palacios, EM; Nitsche, MA; Paulus, W, 2017)	0.46
" Benzodiazepine maintenance would appear an option for the high-dose chaotic abuser, also meeting five criteria, although clinic dosing appears the safest option."	( Which medications are suitable for agonist drug maintenance? Darke, S; Farrell, M, 2016)	0.43
" In Experiment 1, extended training increased rats' sensitivity to nicotine, indicated by a leftward shift in the dose-response curve, and their motivation to work for nicotine, indicated by an increase in the break point achieved under a progressive ratio schedule."	( Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues. Clemens, KJ; Holmes, NM; Lay, BP, 2017)	1.11
"Overall, maternal smoking was associated with change in weight-for-length z-score in a dose-response manner."	( Exposure to Tobacco Metabolites via Breast Milk and Infant Weight Gain: A Population-Based Study. Braid, S; Shenassa, ED; Wen, X, 2016)	0.43
" Although recent work has shown that consumption of plant secondary compounds can reduce pollinator parasite loads, little is known about the effects of dosage or compound combinations."	( Possible Synergistic Effects of Thymol and Nicotine Against Crithidia bombi Parasitism in Bumble Bees. Adler, LS; Biller, OM; Irwin, RE; McAllister, C; Palmer-Young, EC, 2015)	0.68
" Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e."	( A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation. Harris, AC; Muelken, P; Schmidt, CE; Shelley, D; Tally, L, 2015)	0.96
" Then the protein expression level of CCAAT/enhancer binding protein homologous protein (CHOP) was measured by Western blot to define the effect of various concentrations of nicotine and different dosing periods of nicotine on the protein expression level of CHOP."	( [Hydrogen sulfide attenuates bronchial epithelial cell apoptosis by inhibiting endoplasmic reticulum stress]. Bai, Y; Chen, Y; Li, M; Liao, C; Liao, Y; Lin, F; Qi, Y; Sun, Y, 2015)	0.61
" The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers."	( Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences. DeVito, EE; Gueorguieva, R; Jensen, KP; Sofuoglu, M; Valentine, G, 2016)	1.02
" Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse."	( Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window. Hasler, G; Mihov, Y, 2016)	0.43
" Dose-response curves had inverted U shapes, with peak response rates occurring at a dose of 10 μg/kg/injection."	( Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys. Goldberg, SR; Justinova, Z; Makriyannis, A; Redhi, GH; Scherma, M; Schindler, CW; Vadivel, SK, 2016)	0.43
" Dosing was adjusted to produce maternal plasma Nic concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers."	( Cognitive and Behavioral Impairments Evoked by Low-Level Exposure to Tobacco Smoke Components: Comparison with Nicotine Alone. Burke, DA; Cauley, M; Hall, BJ; Kiany, A; Levin, ED; Slotkin, TA, 2016)	0.65
" The results show that (1) tranylcypromine (TCP), a known MAO inhibitor, increases sensitivity to the primary reinforcing effects of nicotine, shifting the dose-response curve for nicotine to the left, (2) inhibition of MAO-A, but not MAO-B, increases low-dose nicotine self-administration, (3) partial MAO-A inhibition, to the degree observed in chronic cigarette smokers, also increases low-dose nicotine self-administration, and (4) TCP decreases the threshold nicotine dose required for reinforcement enhancement."	( Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine. Cwalina, SN; Donny, EC; Murphy, SE; Onimus, MJ; Rupprecht, LE; Smith, TT; Sved, AF, 2016)	0.86
"Nicotine's interoceptive stimulus effects likely help explain smoking's reinforcing efficacy, but human studies have been limited by difficulties controlling dosing via tobacco inhalation."	( Assessing Discrimination of Nicotine in Humans Via Cigarette Smoking. Donny, EC; Karelitz, JL; Kunkle, N; Michael, VC; Perkins, KA, 2016)	2.17
" Component and dose-response studies are needed to establish the potential of EMDR-therapy in smoking cessation."	( Are addiction-related memories malleable by working memory competition? Transient effects on memory vividness and nicotine craving in a randomized lab experiment. Becker, ES; de Weert-van Oene, GH; DeJong, CAJ; Markus, W; Woud, ML, 2016)	0.64
" There was a dose-response relationship between the amount of cigarettes and lysosomal viability; the correlation was higher for cotton samples (r = -0."	( Thirdhand tobacco smoke: procedures to evaluate cytotoxicity in cell cultures. Dantas, DC; Figueiró, LR; Linden, R; Ziulkoski, AL, 2016)	0.43
"015 mg/kg/infusion nicotine, menthol dose-response function was determined."	( Enhancing effect of menthol on nicotine self-administration in rats. Avusula, R; Biswas, L; Gong, Y; Harrison, E; Lage, J; Lee, J; Liu, X; Rousselle, T; Zhang, M, 2016)	1.05
"An inverted U-shaped nicotine dose-response curve was observed."	( Enhancing effect of menthol on nicotine self-administration in rats. Avusula, R; Biswas, L; Gong, Y; Harrison, E; Lage, J; Lee, J; Liu, X; Rousselle, T; Zhang, M, 2016)	1.04
" As a result of this increased intake, the cocaine self-administration dose-response curve was shifted upward indicating an increase in cocaine reinforcement."	( Nicotine produces long-term increases in cocaine reinforcement in adolescent but not adult rats. Izenwasser, S; Reed, SC, 2017)	1.9
" Furthermore, when dosing was discontinued after ten once-daily doses, all nicotine groups (nicotine-only and nicotine+naloxone combination) demonstrated significant decreases in sucrose reinforcement compared to the saline group."	( Nicotine enhancement and reinforcer devaluation: Interaction with opioid receptors. Kirshenbaum, AP; Phillips, JL; Suhaka, JA; Voltolini de Souza Pinto, M, )	1.8
" Dose-response modelling of human and animal data was used to derive the benchmark dose."	( Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine. Baumung, C; Franke, H; Lachenmeier, DW; Rehm, J, 2016)	0.64
" The lack of reliable subjective effects may be the product of the dosing regimen or the relatively small sample size."	( Acute effects of snus in never-tobacco users: a pilot study. Blank, MD; Elswick, D; Felicione, NJ; Ozga, JE, 2018)	0.48
" However oral dosing is the preferred route clinically."	( Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats. Cauley, MC; Glick, S; Levin, ED; Rezvani, AH; Rose, JE; Slade, S; Wells, C, )	0.36
" After a daily dosing regimen, a shift to excitatory-inhibitory balance in single-unit activity and stronger gamma oscillations began to emerge."	( Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention. Bueno-Junior, LS; Moghaddam, B; Simon, NW; Wegener, MA, 2017)	0.87
" Data from the Flexible and Extended Dosing of Nicotine Replacement Therapy (NRT) and Varenicline in Comparison to Fixed Dose NRT for Smoking Cessation: The FLEX Trial, a randomized control trial for smoking cessation, was used to assess the factor structure of the Smoking Cessation Self-Efficacy Questionnaire (SEQ-12), a 12-item scale assessing an individual's confidence to refrain from smoking."	( Factor structure of the Smoking Cessation Self-Efficacy Questionnaire among smokers with and without a psychiatric diagnosis. Clyde, M; Els, C; Pipe, A; Reid, R; Tulloch, H, 2017)	0.71
" Participants indicated that they would require training in the form of information packs (88%), online tutorials (67%), continuous professional development (CPD) workshops (43%) to cover safety, counselling, dosage instructions, adverse effects and role in the smoking cessation care pathway in the future."	( Survey of community pharmacists' perception of electronic cigarettes in London. Buonocore, F; Calabrese, G; Kayyali, R; Marques Gomes, AC; Nabhani-Gebara, S, 2016)	0.43
" We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies."	( Combination nicotine replacement therapy: strategies for initiation and tapering. Chen, TC; Hsia, SL; Myers, MG, 2017)	0.83
" Further, these animals showed a small but significantly increased responding for nicotine during self-administration acquisition, although there was no difference in dose-response effect or in progressive ratio testing."	( Nicotine self-administration reverses cognitive deficits in a rat model for schizophrenia. Brennan, KA; Ellenbroek, BA; Waterhouse, U, 2018)	2.15
" Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors."	( Revisiting nicotine's role in the ageing brain and cognitive impairment. Kamari, F; Majdi, A; Sadigh-Eteghad, S; Vafaee, MS, 2017)	1.25
"38 mg/kg dosage of menthol."	( Menthol enhances nicotine-induced locomotor sensitization and in vivo functional connectivity in adolescence. Colon-Perez, L; Dávila-García, MI; DiFranza, JR; Dubuke, ML; Febo, M; Huang, W; King, JA; Poirier, GL; Robidoux, M; Shaffer, SA; Tam, K; Thompson, MF, 2018)	0.82
" This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks."	( High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Audureau, E; Cormier-Dequaire, F; Damier, P; Defer, G; Evangelista, E; Fénelon, G; Gurruchaga, JM; Itti, E; Kerschen, P; Paul, M; Quéré-Carne, M; Remy, P; Straczek, C; Thiriez, C; Van Der Gucht, A; Villafane, G, 2018)	0.8
" It is recommended to adjust the dosage of nicotine replacement therapy according to the symptoms of under or over dosage at the end of the first week of use."	( [Smoking cessation and pregnancy]. Jaafari, N; Peiffer, G; Perriot, J; Pourrat, O; Underner, M, 2017)	0.72
" Further research should examine possible sex differences in nicotine dosing administered by other smoked and nonsmoked methods, as well as the developmental pattern of these differences during onset and during cessation of dependent smoking."	( Sex Differences in Subjective Responses To Moderate Versus Very Low Nicotine Content Cigarettes. Karelitz, JL; Kunkle, N; Perkins, KA, 2018)	0.96
" These results with research cigarettes are similar to other studies with carefully dosed nicotine administration by other means, supporting the notion that women, relative to men, are less sensitive to pharmacological factors and more sensitive to nonpharmacological factors in acute cigarette smoking."	( Sex Differences in Subjective Responses To Moderate Versus Very Low Nicotine Content Cigarettes. Karelitz, JL; Kunkle, N; Perkins, KA, 2018)	0.94
" 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)	0.96
" Based on dose-response of γH2AX and Hill model, the ability to induce DSBs was evaluated: NNN-acetate > B[a]P > NNK-acetate > tar > nicotine."	( Genotoxicity analysis of five particle matter toxicants from cigarette smoke based on γH2AX assay combined with Hill/Two-component model. Chen, H; Hou, H; Hu, Q; Liu, Y; Wang, A; Zhang, S, 2018)	0.68
"We used Wistar rats which were dosed with cocaine, nicotine or cocaine and nicotine combination and recorded their locomotor activity in different phases of the experiment."	( Cocaine + nicotine mixture enhances induction and expression of behavioral sensitization in rats. Barbosa-Méndez, S; Salazar-Juárez, A, 2018)	1.14
" Yet, nonsmoked nicotine, including from NRT medications of patch and nasal spray, may act more selectively across rewards, perhaps due to lower dosing exposure."	( Reinforcement Enhancing Effects of Nicotine Via Patch and Nasal Spray. Boldry, MC; Karelitz, JL; Perkins, KA, 2019)	1.14
"In this study, we evaluated the effect of chronic dosing of mirtazapine during extinction on the re-acquisition of nicotine-seeking in rodents."	( Mirtazapine attenuates nicotine-seeking behavior in rats. Barbosa-Méndez, S; Salazar-Juárez, A, 2018)	1
"Drug dosage (contains nicotine or not) was crossed with instructional set (told nicotine or non-nicotine) during ad lib e-cigarette use sessions by 128 current e-cigarette users (52 identifying as current cigarette smokers or "dual users")."	( How do electronic cigarettes affect cravings to smoke or vape? Parsing the influences of nicotine and expectancies using the balanced-placebo design. Brandon, TH; Palmer, AM, 2018)	1.02
" Since there was a variation among the included studies regarding nicotine dosage and the duration and magnitude of force application during OTM only a qualitative analysis could be performed."	( Influence of nicotine on orthodontic tooth movement: A systematic review of experimental studies in rats. Akram, Z; Al-Shammery, D; Javed, F; Khan, J; Michelogiannakis, D; Romanos, GE; Rossouw, PE, 2018)	1.09
" Findings also suggest its applicability with testing discrimination of nicotine via other methods of rapid dosing (e."	( Discrimination of nicotine content in electronic cigarettes. Herb, T; Karelitz, JL; Perkins, KA, 2019)	1.08
" Given that individuals who smoke a greater number of tobacco cigarettes are more likely to try e-cigarettes, greater attention to nicotine dosing is necessary."	( Barriers to electronic cigarette use. English, TM; Smith, TB; Song, X; Whitman, MV, 2018)	0.69
" Under medium dosage (but not under low and high dosage) of FLU combined with NIC, plasticity was re-established."	( Nicotine modulates human brain plasticity via calcium-dependent mechanisms. Barlay, J; Batsikadze, G; Grundey, J; Kuo, MF; Nitsche, M; Paulus, W, 2018)	1.92
" In light of this, a range of illicit drugs was researched focusing on pharmacodynamics, usual method of administration, the dosage required for toxicity, toxic effects, and evidence of existing use in e-cigarettes in both literature and online illicit drug forums."	( E-cigarettes-An unintended illicit drug delivery system. Breitbarth, AK; Jones, AL; Morgan, J, 2018)	0.48
" hBE cells were subsequently exposed to various concentrations of cinnamaldehyde to establish a dose-response relationship for effects on CBF."	( Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function. Carson, JL; Clapp, PW; Jaspers, I; Lavrich, KS; Lazarowski, ER; van Heusden, CA, 2019)	0.51
" Furthermore, nicotine reduced sensitivity to EtOH-induced CTA, as indicated by a rightward shift in the dose-response curve of passively administered EtOH."	( Nicotine Produces a High-Approach, Low-Avoidance Phenotype in Response to Alcohol-Associated Cues in Male Rats. Angelyn, H; Cleary, LM; Loney, GC; Meyer, PJ, 2019)	2.32
" On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing."	( A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior. Babalonis, S; Comer, SD; Fraser, H; Jones, JD; Kelsh, D; Lofwall, MR; Marcus, R; Martinez, DM; Martinez, S; Nunes, EV; Paterson, B; Vince, B; Walsh, SL, 2020)	0.56
" Our results showed that overall, nicotine induced significant place preference acquisition and swim stress-induced reinstatement in both male and female mice, but with different nicotine dose-response patterns."	( Variability in nicotine conditioned place preference and stress-induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine. Calarco, CA; Lee, AM; McKee, SA; Mineur, YS; Picciotto, MR, 2020)	1.19
" Pre-clinical proof of concept has been previously established through dosing the amine oxidase NicA2 from Pseudomonas putida in rat nicotine self-administration models of addiction."	( Optimization of a nicotine degrading enzyme for potential use in treatment of nicotine addiction. Ahmed, SS; Biesova, Z; Horrigan, SK; Kalnik, MW; Reed, C; Rodnick-Smith, M; Stone, E; Thisted, T; Van Engelen, B; Walmacq, C, 2019)	1.05
" Dose-response functions for tail-withdrawal latency and operant performance were determined for fentanyl, oxycodone, buprenorphine, and nalbuphine alone and after treatment with nicotine."	( Enhancement of Opioid Antinociception by Nicotine. Barreto de Moura, F; Bergman, J; Withey, SL, 2019)	0.97
" Nicotine plasma levels, and no group differences in effects of nicotine on heart rate or blood pressure, confirmed comparable dosing exposure across groups."	( Increased subjective and reinforcing effects of initial nicotine exposure in young adults with attention deficit hyperactivity disorder (ADHD) compared to matched peers: results from an experimental model of first-time tobacco use. Kollins, SH; McClernon, FJ; Perkins, KA; Sweitzer, MM, 2020)	1.71
" The effective dosage of bupropion increased responding for cocaine alone, nicotine alone, and for saline injections and significantly increased measures of daily activity."	( Effects of chronic treatment with bupropion on self-administration of nicotine + cocaine mixtures in nonhuman primates. Barkin, CE; Blough, BE; Carroll, FI; de Moura, FB; Kohut, SJ; Mello, NK, 2020)	1.02
" The Science Panel from the Alliance of Risk Assessment have convened at the "Beyond Science and Decisions: From Problem Formulation to Dose-Response Assessment" workshop to evaluate modeling approaches and address derivation of exposure-internal dose estimations for inhaled aerosols containing nicotine or other substances."	( Bridging inhaled aerosol dosimetry to physiologically based pharmacokinetic modeling for toxicological assessment: nicotine delivery systems and beyond. Hayes, AW; Hoeng, J; Kolli, AR; Kuczaj, AK; Martin, F; Peitsch, MC, 2019)	0.9
" Nazartinib (at seven dose levels between 75 mg and 350 mg, in capsule or tablet form) was administered orally, once daily, on a continuous 28-day dosing schedule."	( Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study. Aix, SP; Felip, E; Jonnaert, M; Kim, DW; Ko, J; Leighl, NB; Moody, SE; Pan, C; Riely, GJ; Sequist, LV; Seto, T; Tan, DS; Tan, EY; Wolf, J; Yang, JC, 2020)	0.56
"We demonstrate that nicotine potentiates the growth of the lung epithelial cells in a dose-response fashion."	( Nicotine exposure potentiates lung tumorigenesis by perturbing cellular surveillance. Avraham, H; Chen, C; Ganapathy, S; Nishioka, T; Zhang, Q, 2020)	2.32
" The impact of pH, temperature, adsorbent dosage and thermodynamic studies were deeply analyzed."	( Removal of caffeine, nicotine and amoxicillin from (waste)waters by various adsorbents. A review. Anastopoulos, I; Bonilla-Petriciolet, A; Manariotis, ID; Mittal, A; Núñez-Delgado, A; Orfanos, AG; Pashalidis, I; Sellaoui, L; Tatarchuk, T, 2020)	0.88
"Nicotine gum (2 mg) versus placebo for up to 8 weeks, with as-needed dosing instructions."	( Effectiveness of nicotine gum in preventing lapses in the face of temptation to smoke among non-daily smokers: a secondary analysis. Ferguson, SG; Hedeker, D; Mao, J; Scholl, SM; Shiffman, S; Tindle, HA, 2020)	2.34
" Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level."	( Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study. Hand, D; Kranzler, HR; Lynch, KG; Oncken, C; Schnoll, R; Tyndale, RF; Washio, Y; Zindel, LR, 2020)	0.79
"Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner."	( Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma. Ben, Q; Liu, J; Sun, Y; Wang, W; Yuan, Y; Zou, D, 2020)	3.44
" The two compounds were characterised by an inverted U-shaped dose-response curve, and their effects were blocked by the co-administration of the antagonist MCL-117, which alone had no effect."	( Behavioural and pharmacological profiles of zebrafish administrated pyrrolidinyl benzodioxanes and prolinol aryl ethers with high affinity for heteromeric nicotinic acetylcholine receptors. Appiani, R; Bavo, F; Bolchi, C; Braida, D; Gotti, C; Moretti, M; Pallavicini, M; Ponzoni, L; Sala, M; Viani, P, 2020)	0.56
"Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634)."	( Abbasi, S; Abd El-Wahab, A; Abdallah, M; Abebe, G; Aca-Aca, G; Adama, S; Adefegha, SA; Adidigue-Ndiome, R; Adiseshaiah, P; Adrario, E; Aghajanian, C; Agnese, W; Ahmad, A; Ahmad, I; Ahmed, MFE; Akcay, OF; Akinmoladun, AC; Akutagawa, T; Alakavuklar, MA; Álava-Rabasa, S; Albaladejo-Florín, MJ; Alexandra, AJE; Alfawares, R; Alferiev, IS; Alghamdi, HS; Ali, I; Allard, B; Allen, JD; Almada, E; Alobaid, A; Alonso, GL; Alqahtani, YS; Alqarawi, W; Alsaleh, H; Alyami, BA; Amaral, BPD; Amaro, JT; Amin, SAW; Amodio, E; Amoo, ZA; Andia Biraro, I; Angiolella, L; Anheyer, D; Anlay, DZ; Annex, BH; Antonio-Aguirre, B; Apple, S; Arbuznikov, AV; Arinsoy, T; Armstrong, DK; Ash, S; Aslam, M; Asrie, F; Astur, DC; Atzrodt, J; Au, DW; Aucoin, M; Auerbach, EJ; Azarian, S; Ba, D; Bai, Z; Baisch, PRM; Balkissou, AD; Baltzopoulos, V; Banaszewski, M; Banerjee, S; Bao, Y; Baradwan, A; Barandika, JF; Barger, PM; Barion, MRL; Barrett, CD; Basudan, AM; Baur, LE; Baz-Rodríguez, SA; Beamer, P; Beaulant, A; Becker, DF; Beckers, C; Bedel, J; Bedlack, R; Bermúdez de Castro, JM; Berry, JD; Berthier, C; Bhattacharya, D; Biadgo, B; Bianco, G; Bianco, M; Bibi, S; Bigliardi, AP; Billheimer, D; Birnie, DH; Biswas, K; Blair, HC; Bognetti, P; Bolan, PJ; Bolla, JR; Bolze, A; Bonnaillie, P; Borlimi, R; Bórquez, J; Bottari, NB; Boulleys-Nana, JR; Brighetti, G; Brodeur, GM; Budnyak, T; Budnyk, S; Bukirwa, VD; Bulman, DM; Burm, R; Busman-Sahay, K; Butcher, TW; Cai, C; Cai, H; Cai, L; Cairati, M; Calvano, CD; Camacho-Ordóñez, A; Camela, E; Cameron, T; Campbell, BS; Cansian, RL; Cao, Y; Caporale, AS; Carciofi, AC; Cardozo, V; Carè, J; Carlos, AF; Carozza, R; Carroll, CJW; Carsetti, A; Carubelli, V; Casarotta, E; Casas, M; Caselli, G; Castillo-Lora, J; Cataldi, TRI; Cavalcante, ELB; Cavaleiro, A; Cayci, Z; Cebrián-Tarancón, C; Cedrone, E; Cella, D; Cereda, C; Ceretti, A; Ceroni, M; Cha, YH; Chai, X; Chang, EF; Chang, TS; Chanteux, H; Chao, M; Chaplin, BP; Chaturvedi, S; Chaturvedi, V; Chaudhary, DK; Chen, A; Chen, C; Chen, HY; Chen, J; Chen, JJ; Chen, K; Chen, L; Chen, Q; Chen, R; Chen, SY; Chen, TY; Chen, WM; Chen, X; Chen, Y; Cheng, G; Cheng, GJ; Cheng, J; Cheng, YH; Cheon, HG; Chew, KW; Chhoker, S; Chiu, WN; Choi, ES; Choi, MJ; Choi, SD; Chokshi, S; Chorny, M; Chu, KI; Chu, WJ; Church, AL; Cirrincione, A; Clamp, AR; Cleff, MB; Cohen, M; Coleman, RL; Collins, SL; Colombo, N; Conduit, N; Cong, WL; Connelly, MA; Connor, J; Cooley, K; Correa Ramos Leal, I; Cose, S; Costantino, C; Cottrell, M; Cui, L; Cundall, J; Cutaia, C; Cutler, CW; Cuypers, ML; da Silva Júnior, FMR; Dahal, RH; Damiani, E; Damtie, D; Dan-Li, W; Dang, Z; Dasa, SSK; Davin, A; Davis, DR; de Andrade, CM; de Jong, PL; de Oliveira, D; de Paula Dorigam, JC; Dean, A; Deepa, M; Delatour, C; Dell'Aiera, S; Delley, MF; den Boer, RB; Deng, L; Deng, Q; Depner, RM; Derdau, V; Derici, U; DeSantis, AJ; Desmarini, D; Diffo-Sonkoue, L; Divizia, M; Djenabou, A; Djordjevic, JT; Dobrovolskaia, MA; Domizi, R; Donati, A; Dong, Y; Dos Santos, M; Dos Santos, MP; Douglas, RG; Duarte, PF; Dullaart, RPF; Duscha, BD; Edwards, LA; Edwards, TE; Eichenwald, EC; El-Baba, TJ; Elashiry, M; Elashiry, MM; Elashry, SH; Elliott, A; Elsayed, R; Emerson, MS; Emmanuel, YO; Emory, TH; Endale-Mangamba, LM; Enten, GA; Estefanía-Fernández, K; Estes, JD; Estrada-Mena, FJ; Evans, S; Ezra, L; Faria de, RO; Farraj, AK; Favre, C; Feng, B; Feng, J; Feng, L; Feng, W; Feng, X; Feng, Z; Fernandes, CLF; Fernández-Cuadros, ME; Fernie, AR; Ferrari, D; Florindo, PR; Fong, PC; Fontes, EPB; Fontinha, D; Fornari, VJ; Fox, NP; Fu, Q; Fujitaka, Y; Fukuhara, K; Fumeaux, T; Fuqua, C; Fustinoni, S; Gabbanelli, V; Gaikwad, S; Gall, ET; Galli, A; Gancedo, MA; Gandhi, MM; Gao, D; Gao, K; Gao, M; Gao, Q; Gao, X; Gao, Y; Gaponenko, V; Garber, A; Garcia, EM; García-Campos, C; García-Donas, J; García-Pérez, AL; Gasparri, F; Ge, C; Ge, D; Ge, JB; Ge, X; George, I; George, LA; Germani, G; Ghassemi Tabrizi, S; Gibon, Y; Gillent, E; Gillies, RS; Gilmour, MI; Goble, S; Goh, JC; Goiri, F; Goldfinger, LE; 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Xun, J; Yaffe, MB; Yalew, A; Yamamoto, S; Yan, D; Yan, H; Yan, S; Yan, X; Yang, AD; Yang, E; Yang, H; Yang, J; Yang, JL; Yang, K; Yang, M; Yang, P; Yang, Q; Yang, S; Yang, W; Yang, X; Yang, Y; Yao, JC; Yao, WL; Yao, Y; Yaqub, TB; Ye, J; Ye, W; Yen, CW; Yeter, HH; Yin, C; Yip, V; Yong-Yi, J; Yu, HJ; Yu, MF; Yu, S; Yu, W; Yu, WW; Yu, X; Yuan, P; Yuan, Q; Yue, XY; Zaia, AA; Zakhary, SY; Zalwango, F; Zamalloa, A; Zamparo, P; Zampini, IC; Zani, JL; Zeitoun, R; Zeng, N; Zenteno, JC; Zepeda-Palacio, C; Zhai, C; Zhang, B; Zhang, G; Zhang, J; Zhang, K; Zhang, Q; Zhang, R; Zhang, T; Zhang, X; Zhang, Y; Zhang, YY; Zhao, B; Zhao, D; Zhao, G; Zhao, H; Zhao, Q; Zhao, R; Zhao, S; Zhao, T; Zhao, X; Zhao, XA; Zhao, Y; Zhao, Z; Zheng, Z; Zhi-Min, G; Zhou, CL; Zhou, HD; Zhou, J; Zhou, W; Zhou, XQ; Zhou, Z; Zhu, C; Zhu, H; Zhu, L; Zhu, Y; Zitzmann, N; Zou, L; Zou, Y, 2022)	0.72
" The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine's neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects."	( Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine. Perkins, KA, 2022)	1.5
" Our HTS efforts included single-dose and 16-point dose-response curves, which allowed testing of ≥90 commercially available e-liquids in parallel to provide a rapid assessment of cellular effects as a proof of concept for a fast, preliminary toxicity method."	( Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cellular Membrane Potential Are Predictors of E-Liquid Induced Cellular Toxicity. Correia-Álvarez, E; Glish, G; Keating, JE; Sassano, MF; Tarran, R, 2020)	0.56
"0, 10, and 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward."	( Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex. King, CP; Loney, GC; Meyer, PJ, 2021)	1.04
" There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD."	( Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats. Boomhower, B; Carrette, LLG; Dowling, J; Fitzgerald, RL; George, O; Hanham, K; Hoffman, M; Kallupi, M; Momper, JD; Sepulveda, Y; Smith, LC; Suhandynata, RT; Tieu, L, 2021)	0.88
" Preclinical research is imperative for understanding the addictive properties and health-risks associated with ECIG use; however, there is not a standard dosing regimen used across research laboratories."	( Nicotine-free vapor inhalation produces behavioral disruptions and anxiety-like behaviors in mice: Effects of puff duration, session length, sex, and flavor. Allen, N; Barraza, AG; Dewey, M; Garrett, PI; Hillhouse, TM; Honeycutt, SC; Marston, C; Peterson, AM; Turner, B, 2021)	2.06
" The 2 most potent nic•mAbs in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study."	( Attenuating nicotine's effects with high affinity human anti-nicotine monoclonal antibodies. Beltraminelli, N; Biesova, Z; Fallot, S; Fuller, S; Horrigan, S; Kalnik, MW; LeSage, MG; Pentel, PR; Raleigh, MD; Sampey, D; Saykao, A; Thisted, T; Zhou, B, 2021)	1.26
"The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes."	( Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review. Alyusuf, AH; Atreyapurapu, S; Chang, KHK; Finnegan, LP; Isaacs, KR; Ledgerwood, DM; Ma, TX; Washio, Y, 2021)	1.19
" Although Raman spectroscopy has been used for such characterization of numerous dosage forms, its applicability to medicated chewing gum has not been studied until now."	( Raman Imaging as a powerful tool to elucidate chemical processes in a matrix: Medicated chewing gums with nicotine. Bauer-Brandl, A; Nielsen, KA; Poulsen, J, 2022)	0.93
"6%), dosage (25%), and contraindications (36."	( Knowledge, Attitude, Practices, and Preparedness of Dental Professionals in Prescribing Nicotine Replacement Therapy. Kashyap, P; Kataria, S; Mahapatra, S; Marya, A; Marya, CM; Nagpal, R; Taneja, P, 2022)	0.94
" Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test."	( Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans. De Aquino, JP; DeVito, EE; Gueorguieva, R; Meyerovich, J; Parida, S; Sofuoglu, M; Xie, C, 2022)	1
" Memantine demonstrated a bell-shaped dose-response curve of NP against NMDA."	( Memantine has a nicotinic neuroprotective pathway in acute hippocampal slices after an NMDA insult. Eterovic, VA; Ferchmin, PA; Ferrer-Acosta, Y; Martins, AH; Pérez, D; Rodriguez-Massó, S, 2022)	0.72
"The quantitative analysis of neurological drugs is critical since the kinetics of body fluids is strongly dependent on the dosage of the drug levels."	( 2D MXene/graphene nanocomposite preparation and its electrochemical performance towards the identification of nicotine level in human saliva. Atchudan, R; Ganapathy, D; Habila, MA; Nallaswamy, D; Rajendran, J; Sundramoorthy, AK, 2022)	0.93
"Compared with mono-culture, cell proliferation increased, apoptosis decreased, and DNA damage decreased in a dose-response relationship in co-culture."	( Acute cytotoxicity test of PM Chen, Y; Du, Y; Huang, Z; Liang, L; Liu, J; Liu, Y; Xie, R; Yang, Q; Zhou, J; Zou, H, 2022)	0.72
" In this article, we chose nicotine levels as dosing references and C57BL/6 mice for a 10-week subchronic inhalation toxicity study."	( Combined biological effects and lung proteomics analysis in mice reveal different toxic impacts of electronic cigarette aerosol and combustible cigarette smoke on the respiratory system. Chen, J; Duan, K; Huang, G; Jiang, L; Jiang, X; Li, M; Liu, P; Song, H; Yang, W; Yang, X, 2022)	1.02
" NRT dosing is imprecise, however, and there is some evidence that patients and providers are reluctant to use the larger doses that may be appropriate for some people who smoke."	( Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study. Behal, A; Selby, P; Veldhuizen, S; Zawertailo, L, 2023)	1.29
" Dose-response curves derived from our model showed that initial doses below about 2 mg/CPD/day were associated with poorer outcomes."	( Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study. Behal, A; Selby, P; Veldhuizen, S; Zawertailo, L, 2023)	1.29
" The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose-response analysis."	( Association of the American Heart Association's new "Life's Essential 8" with all-cause and cardiovascular disease-specific mortality: prospective cohort study. Li, Y; Magnussen, CG; Sun, J; Xi, B; Yu, X; Zhang, C; Zhao, M, 2023)	0.91
" There were approximately linear dose-response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality."	( Association of the American Heart Association's new "Life's Essential 8" with all-cause and cardiovascular disease-specific mortality: prospective cohort study. Li, Y; Magnussen, CG; Sun, J; Xi, B; Yu, X; Zhang, C; Zhao, M, 2023)	0.91
" Given the much lower cost of cytisine treatment, its lower rate of adverse events, and higher feasibility (but its likely lower effectiveness with the standard dosage regimen), future analyses should assess the cost-effectiveness of the two treatments for health policy considerations."	( Cytisine Versus Varenicline for Smoking Cessation in a Primary Care Setting: A Randomized Non-inferiority Trial. Ashburner, JM; Klemenc Ketiš, Z; Oreskovic, S; Oreskovic, T; Percac-Lima, S; Rifel, J; Tiljak, H, 2023)	0.91
" Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal."	( Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. Benowitz, NL; Blumenstein, B; Cain, D; Clarke, A; Jacobs, C; Leischow, S; Nides, M; Prochaska, J; Rigotti, NA, 2023)	0.91
"To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo."	( Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. Benowitz, NL; Blumenstein, B; Cain, D; Clarke, A; Jacobs, C; Leischow, S; Nides, M; Prochaska, J; Rigotti, NA, 2023)	0.91
" 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)	2.59