caffeine has been researched along with fluoxetine in 43 studies
Timeframe | Studies, this research(%) | All Research% |
---|---|---|
pre-1990 | 1 (2.33) | 18.7374 |
1990's | 7 (16.28) | 18.2507 |
2000's | 9 (20.93) | 29.6817 |
2010's | 21 (48.84) | 24.3611 |
2020's | 5 (11.63) | 2.80 |
Authors | Studies |
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Topliss, JG; Yoshida, F | 1 |
Ahman, M; Holmén, AG; Wan, H | 1 |
Barnes, JC; Bradley, P; Day, NC; Fourches, D; Reed, JZ; Tropsha, A | 1 |
Choi, SS; Contrera, JF; Hastings, KL; Kruhlak, NL; Sancilio, LF; Weaver, JL; Willard, JM | 1 |
Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ | 1 |
Glen, RC; Lowe, R; Mitchell, JB | 1 |
Afshari, CA; Eschenberg, M; Hamadeh, HK; Lee, PH; Lightfoot-Dunn, R; Morgan, RE; Qualls, CW; Ramachandran, B; Trauner, M; van Staden, CJ | 1 |
Ekins, S; Williams, AJ; Xu, JJ | 1 |
Boriss, H; Braggio, S; Corbioli, S; Fontana, S; Helmdach, L; Longhi, R; Schiller, J; Vinco, F | 1 |
Sen, S; Sinha, N | 1 |
Honda, K; Izumi, T; Miyaji, Y; Nakayama, S; Okazaki, O; Okudaira, N; Shiosakai, K; Sugiyama, D; Suzuki, W; Takakusa, H; Watanabe, A | 1 |
Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR | 1 |
Ambroso, JL; Ayrton, AD; Baines, IA; Bloomer, JC; Chen, L; Clarke, SE; Ellens, HM; Harrell, AW; Lovatt, CA; Reese, MJ; Sakatis, MZ; Taylor, MA; Yang, EY | 1 |
Cantin, LD; Chen, H; Kenna, JG; Noeske, T; Stahl, S; Walker, CL; Warner, DJ | 1 |
Afshari, CA; Chen, Y; Dunn, RT; Hamadeh, HK; Kalanzi, J; Kalyanaraman, N; Morgan, RE; van Staden, CJ | 1 |
Chen, M; Hu, C; Suzuki, A; Thakkar, S; Tong, W; Yu, K | 1 |
Gibaldi, M | 1 |
Burket, RC; Hodgin, JD | 1 |
Callaway, CW; Geyer, MA; Rempel, NL | 1 |
Brøsen, K; Gram, LF; Jeppesen, U; Loft, S; Poulsen, HE; Vistisen, K | 1 |
Borrell, L; Foreyt, JP; Haddock, CK; Poston, WS | 1 |
Aunis, D; Burgun, C; Humblot, N; Thiriet, N; Zwiller, J | 1 |
Kaneko, S; Kawata, Y; Kondo, T; Mizuno, K; Murakami, T; Okada, M; Wada, K | 1 |
Esser, MJ; Reid, AR; Sawynok, J | 1 |
Liang, JH; Liu, RK; Sun, HL; Wang, XH; Ye, XF; Zheng, JW | 1 |
Caboche, J; Girault, JA; Hervé, D; Pagès, C; Valjent, E | 1 |
Hong, Z; Kelly, RF; Lang, IM; Murar, J; Nelson, DP; Rezaie-Majd, S; Varghese, A; Weir, EK | 1 |
Alici, T; Aygoren, MO; Kayir, H; Saglam, E; Uzbay, IT | 1 |
André, C; Blaise, C; Gagné, F; Salazar, M | 1 |
Amri, H; Bartels, BK; Beeson, E; Bergner, CL; Cachat, JM; Canavello, PR; Egan, RJ; Elegante, MF; Elkhayat, SI; Glasgow, E; Hart, PC; Kalueff, AV; Mohnot, S; Tien, AK; Tien, DH; Zukowska, Z | 1 |
Colwill, RM; Creton, R; Pelkowski, SD; Richendrfer, H | 1 |
Amaral, VC; Campos, KF; Miguel, TT; Nunes-de-Souza, RL; Rico, JL | 1 |
Bohner, LO; Costa, AP; De Lima, TC; Lino-de-Oliveira, C; Santos, EC; Silva, CF; Vieira, C | 1 |
Baca, S; Martinez Gomez, DA; Walsh, EJ | 1 |
Carrilho, MC; Francisco, RP; Krebs, VL; Lopes, LM; Lopes, MA; Zugaib, M | 1 |
Aickareth, G; Bajaj, R; Durgam, A; Jamal, F; Mathews, M | 1 |
Doboszewska, U; Dudka, J; Herbet, M; Kanadys, A; Korga, A; Ostrowska, M; Poleszak, E; Serefko, A; Świąder, K; Szopa, A; Terlecka, J; Wlaź, A; Wlaź, P; Wośko, S; Wróbel, A; Wyska, E | 1 |
Afsa, S; Hamden, K; Lara Martin, PA; Mansour, HB | 1 |
Akerman, J; González Cautela, BV; Pfaus, JG; Quintana, GR | 1 |
Brandão, CJ; de Souza, RC; Dos Santos, TL; Godoy, AA; Kummrow, F; Pinto, E | 1 |
Baldinelli, A; Battistoni, G; Ciavattini, A; Delli Carpini, G; Di Giuseppe, J; Giannella, L; Montironi, R; Pozzi, M | 1 |
Ghasemi, JB; Hosseini, E; Shekarchi, M | 1 |
Cho, YS; Hwang, EM; Jung, SY; Lim, SM; Min, SJ; Pae, AN; Park, KD; Viswanath, AN | 1 |
4 review(s) available for caffeine and fluoxetine
Article | Year |
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DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Preparations; Risk | 2016 |
Drug interactions: Part I.
Topics: Antidepressive Agents, Tricyclic; Caffeine; Cimetidine; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Enzyme Induction; Fluconazole; Fluoxetine; Hexobarbital; Humans; Ketoconazole; Nimodipine; Oxidoreductases; Pharmaceutical Preparations; Rifampin; Stereoisomerism; Warfarin; Zidovudine | 1992 |
Challenges in obesity management.
Topics: 1-Naphthylamine; Adrenergic beta-Agonists; Appetite Depressants; Behavior Therapy; Caffeine; Cyclobutanes; Diethylpropion; Ephedrine; Fenfluramine; Fluoxetine; Humans; Lactones; Leptin; Lipase; Obesity; Orlistat; Phentermine; Proteins; Sertraline | 1998 |
Foetal ductus arteriosus constriction unrelated to non-steroidal anti-Inflammatory drugs: a case report and literature review.
Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Caffeine; Cesarean Section; Constriction; Constriction, Pathologic; Ductus Arteriosus; Female; Fluoxetine; Humans; Naphazoline; Pesticides; Pharmaceutical Preparations; Polyphenols; Pregnancy; Solvents; Ultrasonography, Prenatal | 2021 |
1 trial(s) available for caffeine and fluoxetine
Article | Year |
---|---|
Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.
Topics: Adult; Aryl Hydrocarbon Hydroxylases; Caffeine; Chromatography, High Pressure Liquid; Citalopram; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Humans; Male; Mephenytoin; Mixed Function Oxygenases; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sparteine | 1996 |
38 other study(ies) available for caffeine and fluoxetine
Article | Year |
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QSAR model for drug human oral bioavailability.
Topics: Administration, Oral; Biological Availability; Humans; Models, Biological; Models, Molecular; Pharmaceutical Preparations; Pharmacokinetics; Structure-Activity Relationship | 2000 |
Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
Topics: Brain; Central Nervous System; Chromatography, Liquid; Emulsions; Mass Spectrometry | 2009 |
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLINE; Mice; Models, Chemical; Molecular Conformation; Quantitative Structure-Activity Relationship | 2010 |
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
Topics: | 2008 |
Developing structure-activity relationships for the prediction of hepatotoxicity.
Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Humans; Structure-Activity Relationship; Tetracyclines; Thiophenes | 2010 |
Predicting phospholipidosis using machine learning.
Topics: Animals; Artificial Intelligence; Databases, Factual; Drug Discovery; Humans; Lipidoses; Models, Biological; Phospholipids; Support Vector Machine | 2010 |
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Biological Assay; Biological Transport; Cell Line; Cell Membrane; Chemical and Drug Induced Liver Injury; Cytoplasmic Vesicles; Drug Evaluation, Preclinical; Humans; Liver; Rats; Reproducibility of Results; Spodoptera; Transfection; Xenobiotics | 2010 |
A predictive ligand-based Bayesian model for human drug-induced liver injury.
Topics: Bayes Theorem; Chemical and Drug Induced Liver Injury; Humans; Ligands | 2010 |
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
Topics: Absorption; Albumins; Animals; Brain; Brain Chemistry; Cell Membrane; Chromatography, High Pressure Liquid; Drug Evaluation, Preclinical; In Vitro Techniques; Lipids; Male; Microdialysis; Pharmaceutical Preparations; Protein Binding; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Swine; Tissue Distribution | 2011 |
Predicting hERG activities of compounds from their 3D structures: development and evaluation of a global descriptors based QSAR model.
Topics: Computer Simulation; Ether-A-Go-Go Potassium Channels; Humans; Molecular Structure; Organic Chemicals; Quantitative Structure-Activity Relationship | 2011 |
Combination of GSH trapping and time-dependent inhibition assays as a predictive method of drugs generating highly reactive metabolites.
Topics: Glutathione; Pharmacology; Sulfur Radioisotopes | 2011 |
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Topics: Atorvastatin; Biological Transport; Drug Interactions; Estradiol; Estrone; HEK293 Cells; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; In Vitro Techniques; Least-Squares Analysis; Liver; Liver-Specific Organic Anion Transporter 1; Models, Molecular; Multivariate Analysis; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Protein Isoforms; Pyrroles; Solute Carrier Organic Anion Transporter Family Member 1B3; Structure-Activity Relationship; Transfection | 2012 |
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
Topics: Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Decision Trees; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Glutathione; Humans; Liver; Pharmaceutical Preparations; Protein Binding | 2012 |
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Cell Line; Chemical and Drug Induced Liver Injury; Humans; Quantitative Structure-Activity Relationship | 2012 |
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Biological Transport; Chemical and Drug Induced Liver Injury; Cluster Analysis; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Male; Multidrug Resistance-Associated Proteins; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Risk Assessment; Risk Factors; Toxicity Tests | 2013 |
Fluoxetine treatment of a depressed patient susceptible to malignant hyperthermia.
Topics: Adolescent; Caffeine; Depressive Disorder; Disease Susceptibility; Female; Fluoxetine; Halothane; Humans; Malignant Hyperthermia; Muscle Contraction | 1989 |
Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release.
Topics: 3,4-Methylenedioxyamphetamine; Animals; Behavior, Animal; Caffeine; Designer Drugs; Dopamine Agents; Dose-Response Relationship, Drug; Fluoxetine; Indoles; Male; Motor Activity; N-Methyl-3,4-methylenedioxyamphetamine; Nicotine; Propranolol; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Scopolamine; Serotonin; Serotonin Receptor Agonists; Synapses | 1993 |
Cocaine and fluoxetine induce the expression of the hVH-5 gene encoding a MAP kinase phosphatase.
Topics: 5,7-Dihydroxytryptamine; Amphetamine; Animals; Caffeine; Central Nervous System Stimulants; Cocaine; Drug Interactions; Dual-Specificity Phosphatases; Enzyme Induction; Fluoxetine; Genes, Immediate-Early; Immediate-Early Proteins; Male; Nerve Tissue Proteins; Protein Tyrosine Phosphatases; Rats; Rats, Wistar | 1998 |
Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.
Topics: Adenosine; Animals; Antihypertensive Agents; Biological Transport; Caffeine; Central Nervous System Stimulants; Fluoxetine; Hippocampus; Male; Microdialysis; Phenethylamines; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Quipazine; Rats; Rats, Wistar; Receptor, Adenosine A2A; Receptor, Adenosine A3; Receptors, Purinergic P1; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Theobromine; Theophylline; Vasodilator Agents | 1999 |
Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat.
Topics: Adrenergic Uptake Inhibitors; Amitriptyline; Animals; Caffeine; Desipramine; Drug Evaluation, Preclinical; Fluoxetine; Male; Neuralgia; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Spinal Nerves | 1999 |
Buspirone-induced antinociception is mediated by L-type calcium channels and calcium/caffeine-sensitive pools in mice.
Topics: 5-Hydroxytryptophan; Analgesics; Animals; Buspirone; Caffeine; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Chloride; Central Nervous System Stimulants; Chelating Agents; Egtazic Acid; Female; Fluoxetine; Injections, Intraventricular; Mice; Nifedipine; Pain Measurement; Reaction Time; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Ryanodine; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists | 2003 |
Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain.
Topics: Adrenergic Uptake Inhibitors; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Benzazepines; Brain; Caffeine; Central Nervous System Stimulants; Cocaine; Desipramine; Dopamine Antagonists; Dronabinol; Enzyme Activation; Fluoxetine; Immunohistochemistry; Male; Mice; Mitogen-Activated Protein Kinases; Morphine; Muscarinic Antagonists; Neurons; Nicotine; Nicotinic Agonists; Scopolamine; Selective Serotonin Reuptake Inhibitors | 2004 |
Increased release of serotonin from rat ileum due to dexfenfluramine.
Topics: 4-Aminopyridine; Animals; Caffeine; Calcium; Chromatography, High Pressure Liquid; Cytosol; Dexfenfluramine; Fluoxetine; Hypertension, Pulmonary; Ileum; Male; Potassium Channel Blockers; Potassium Channels; Potassium Chloride; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Receptor Agonists | 2004 |
Discriminative stimulus properties of tianeptine.
Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adrenergic Uptake Inhibitors; Animals; Antidepressive Agents; Caffeine; Central Nervous System Stimulants; Conditioning, Operant; Cyclohexanols; Discrimination Learning; Discrimination, Psychological; Fluoxetine; Male; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Thiazepines; Venlafaxine Hydrochloride | 2006 |
Effects of pharmaceutical products and municipal wastewaters on temperature-dependent mitochondrial electron transport activity in Elliptio complanata mussels.
Topics: Bivalvia; Caffeine; Carbamazepine; Cholestanol; Cotinine; Electron Transport; Fluoxetine; Ibuprofen; Lipid Peroxidation; Mitochondria; Novobiocin; Pharmaceutical Preparations; Sewage; Temperature; Trimethoprim; Xenobiotics | 2006 |
Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish.
Topics: Animals; Antidepressive Agents, Second-Generation; Anxiety; Behavior, Animal; Caffeine; Central Nervous System Depressants; Central Nervous System Stimulants; Disease Models, Animal; Ethanol; Female; Fluoxetine; Hydrocortisone; Male; Motor Activity; Phenotype; Pheromones; Species Specificity; Stress, Psychological; Zebrafish | 2009 |
On the edge: pharmacological evidence for anxiety-related behavior in zebrafish larvae.
Topics: Animals; Anxiety; Caffeine; Cues; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fluoxetine; Spatial Behavior; Swimming; Zebrafish | 2012 |
Ethopharmacological evaluation of the rat exposure test: a prey-predator interaction test.
Topics: Adrenergic alpha-2 Receptor Antagonists; Alprazolam; Animals; Anti-Anxiety Agents; Antidepressive Agents; Caffeine; Central Nervous System Stimulants; Diazepam; Escape Reaction; Factor Analysis, Statistical; Fluoxetine; Food Chain; Imipramine; Male; Mice; Motor Activity; Posture; Predatory Behavior; Rats; Rats, Long-Evans; Time Factors; Yohimbine | 2013 |
A proposal for refining the forced swim test in Swiss mice.
Topics: Animals; Antidepressive Agents; Apomorphine; Caffeine; Central Nervous System Stimulants; Desipramine; Disease Models, Animal; Fluoxetine; Imipramine; Immobility Response, Tonic; Male; Mice; Principal Component Analysis; Swimming; Time Factors | 2013 |
Lethal and sublethal effects of selected PPCPs on the freshwater rotifer, Plationus patulus.
Topics: Acetaminophen; Animals; Caffeine; Cosmetics; Fluoxetine; Food Chain; Fresh Water; Lethal Dose 50; Mexico; Pharmaceutical Preparations; Rotifera; Triclosan; Water Pollutants, Chemical; Water Pollution, Chemical | 2015 |
Fetal ductus arteriosus constriction and closure: analysis of the causes and perinatal outcome related to 45 consecutive cases.
Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Flow Velocity; Caffeine; Central Nervous System Stimulants; Constriction, Pathologic; Ductus Arteriosus; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Female; Fluoxetine; Heart Failure; Humans; Hypertension, Pulmonary; Isoxsuprine; Maternal Exposure; Maternal-Fetal Exchange; Naphazoline; Nasal Decongestants; Pesticides; Pregnancy; Remission, Spontaneous; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Tricuspid Valve Insufficiency; Ultrasonography, Prenatal; Vasodilator Agents; Ventricular Dysfunction, Right; Young Adult | 2016 |
A Case of Caffeine Intolerance With Long-Term Use of Fluoxetine.
Topics: Adolescent; Antidepressive Agents, Second-Generation; Caffeine; Central Nervous System Stimulants; Coffee; Depressive Disorder; Drug Interactions; Female; Fluoxetine; Humans | 2017 |
Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression.
Topics: Amino Acid Transport Systems, Neutral; Animals; Antidepressive Agents, Second-Generation; Behavior, Animal; Caffeine; Central Nervous System Stimulants; Cerebral Cortex; Citalopram; Depression; Disease Models, Animal; Drug Administration Schedule; Fluoxetine; Hindlimb Suspension; Male; Mice; Motor Activity; Receptor, Adenosine A1; RNA, Messenger; Selective Serotonin Reuptake Inhibitors; Swimming; Time Factors | 2017 |
Occurrence of 40 pharmaceutically active compounds in hospital and urban wastewaters and their contribution to Mahdia coastal seawater contamination.
Topics: Caffeine; Environmental Monitoring; Fluoxetine; Hospitals; Pharmaceutical Preparations; Salicylic Acid; Seawater; Sulfadiazine; Sulfamethizole; Tunisia; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical | 2020 |
Acute caffeine reverses the disruptive effects of chronic fluoxetine on the sexual behavior of female and male rats.
Topics: Animals; Caffeine; Copulation; Ejaculation; Estradiol; Female; Fluoxetine; Libido; Male; Progesterone; Rats; Rats, Long-Evans; Selective Serotonin Reuptake Inhibitors; Sexual Behavior, Animal | 2021 |
Occurrence of caffeine, fluoxetine, bezafibrate and levothyroxine in surface freshwater of São Paulo State (Brazil) and risk assessment for aquatic life protection.
Topics: Bezafibrate; Brazil; Caffeine; Environmental Monitoring; Fluoxetine; Fresh Water; Risk Assessment; Thyroxine; Water Pollutants, Chemical | 2021 |
Simultaneous Determination of Adulterants in Dietary Food Supplements Using Multivariate Data Analysis after Preconcentration with Novel Nanosorbents and Chromatographic Measurement.
Topics: Caffeine; Chromatography, High Pressure Liquid; Data Analysis; Dietary Supplements; Ephedrine; Fluoxetine | 2022 |
Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.
Topics: Animals; Computer Simulation; Crystallography, X-Ray; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Mice; Mice, Knockout; Molecular Docking Simulation; Potassium Channels, Tandem Pore Domain | 2016 |