Varenicline Is a Partial Agonist at α4β2 and a Full Agonist at α7 Neuronal Nicotinic Receptors
Abstract
Varenicline, a new nicotinic ligand based on the structure of cytisine, has recently been approved by the U.S. Food and Drug Administration for use as a smoking cessation aid. Varenicline has been shown to be a partial agonist of alpha4beta2 receptors, and in equilibrium binding assays, it is highly selective for the alpha4beta2 receptor. In this study, we have examined the functional activity of varenicline at a variety of rat neuronal nicotinic receptors expressed in Xenopus laevis oocytes and assayed under two-electrode voltage clamp. We also find that varenicline is a potent, partial agonist at alpha4beta2 receptors, with an EC50 of 2.3 +/- 0.3 microM and an efficacy (relative to acetylcholine) of 13.4 +/- 0.4%. Varenicline has lower potency and higher efficacy at alpha3beta4 receptors, with an EC50 of 55 +/- 8 microM and an efficacy of 75 +/- 6%. Varenicline also seems to be a weak partial agonist at alpha3beta2 and alpha6-containing receptors, with an efficacy <10%. It is remarkable that varenicline is a potent, full agonist at alpha7 receptors with an EC50 of 18 +/- 6 microM and an efficacy of 93 +/- 7% (relative to acetylcholine). Thus, whereas varenicline is a partial agonist at some heteromeric neuronal nicotinic receptors, it is a full agonist at the homomeric alpha7 receptor. Some combination of these actions may be involved in the mechanism of varenicline as a smoking cessation aid.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Varenicline is a partial agonist of α4/β2* nAChRs but also activates α7-type nAChRs.
“Varenicline is a partial agonist of α4/β2* nAChRs (Coe et al., 2005), but also activates α7-type nAChRs (Mihalak et al., 2006).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Mihalak et al., 2006
At α3β4 receptors varenicline is a weaker partial agonist, while at α7 receptors it is a full agonist.
“Varenicline (Chantix; Pfizer, Groton, CT) is a potent partial agonist at ␣42 nAChRs, with 40 to 60% of the agonist efficacy of nicotine (Rollema et al., 2007), and it is a less potent partial agonist at ␣34 and a full agonist at ␣7 nAChRs (Mihalak et al., 2006;Rollema et al., 2007Rollema et al., , 2009b)).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Mihalak et al., 2006
Varenicline has moderate affinity for other nAChRs and acts as a partial agonist at α3β4 and a full agonist at α7 nAChRs.
“the high-affinity ␣42 partial agonist varenicline also has moderate affinity for other nAChRs and acts as a partial agonist at ␣34 and a full agonist at ␣7 nAChRs (Mihalak et al., 2006;Rollema et al., 2007).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Mihalak et al., 2006
Varenicline is an efficacious treatment for nicotine dependence.
“Varenicline, a partial agonist at the α4β2 nAChRs, and a full agonist at the α7 nAChRs, is a new, efficacious treatment for nicotine dependence (4–6).”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [6]
Varenicline acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a full agonist at α7 nicotinic acetylcholine receptors.
“Varenicline, a partial agonist at the α4β2 nAChRs, and a full agonist at the α7 nAChRs, is a new, efficacious treatment for nicotine dependence (4–6).”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [6]
Varenicline acts as a partial agonist at α3β4-, α2-, and α6-containing nAChRs, and a full agonist at α7 nAChRs.
“It acts as a partial agonist at α3β4-, α2-, and α6-containing nAChRs, and a full agonist at α7 nAChRs [238].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [238]
Varenicline is a derivative of cytisine, a plant alkaloid with selective affinity and partial agonism for α4β2 nAChRs.
“It is a derivative of cytisine, a plant alkaloid with selective affinity and partial agonism for α4β2 nAChRs [236–238].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [238]
Varenicline is a derivative of cytisine, a plant alkaloid with selective affinity and partial agonism for α4β2 nAChRs.
“It is a derivative of cytisine, a plant alkaloid with selective affinity and partial agonism for α4β2 nAChRs [236–238].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [237]
Varenicline has significant effects at α7 nAChRs, α3β4* nAChRs, and 5-hydroxytryptamine type 3 receptors.
“subsequent work showed that varenicline had a significant effect at ␣7 nAChRs, ␣34* nAChRs, and 5-hydroxytryptamine type 3 receptors”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Mihalak et al., 2006
Varenicline, a partial agonist of α4β2 nAChRs and a full α7 agonist developed to aid smoking cessation, has antidepressant effects in the forced swim test.
“varenicline, a partial agonist of the α4β2 nAChRs and a full α7 agonist developed to aid smoking cessation in humans (Mihalak, Carroll, & Luetje, 2006), has also been found to have antidepressant effects in the FST (Rollema et al., 2009).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Mihalak et al., 2006
Cites
Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation
Coe, J. W., Brooks, P. R., Vetelino, M. G., Wirtz, M. C., Arnold, E. P., Huang, J., Sands, S. B., Davis, T. I., Lebel, L. A., Fox, C. B., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050069n · Cited by 930 · see citing works
Nicotinic Receptors at the Amino Acid Level
Corringer, P., Novère, N. G. L., & Changeux, J. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.431 · Cited by 823 · see citing works
Luetje, C., & Patrick, J. (1991) · The Journal of Neuroscience · doi:10.1523/jneurosci.11-03-00837.1991 · Cited by 558 · see citing works
Jensen, A. A., Frølund, B., Liljefors, T., & Krogsgaard‐Larsen, P. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm040219e · Cited by 541 · see citing works
Chavez-Noriega, L. E., Crona, J. H., Washburn, M. S., Urrutia, A., Elliott, K. J., & Johnson, E. C. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36376-1 · Cited by 405 · see citing works
Salminen, O., Murphy, K. L., McIntosh, J. M., Drago, J., Marks, M. J., Collins, A. C., & Grady, S. R. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.6.1526 · Cited by 401 · see citing works
Chavez-Noriega, L. E., Crona, J. H., Washburn, M. S., Urrutia, A., Elliott, K. J., & Johnson, E. C. (1997) · PubMed · Cited by 392 · see citing works
Partial agonist properties of cytisine on neuronal nicotinic receptors containing the beta 2 subunit
Papke, R. L., & Heinemann, S. F. (1994) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09896-7 · Cited by 259 · see citing works
Comparative pharmacology of rat and human α7 nAChR conducted with net charge analysis
Papke, R. L., & Porter Papke, J. K. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704833 · Cited by 249 · see citing works
Human α6 AChR subtypes: subunit composition, assembly, and pharmacological responses
Kuryatov, A., Olale, F., Cooper, J., Choi, C. H., & Lindstrom, J. M. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00144-1 · Cited by 223 · see citing works
Obach, R. S., Reed‐Hagen, A. E., Krueger, S. S., Obach, B. J., O’Connell, T. N., Zandi, K. S., Miller, S., & Coe, J. W. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.006767 · Cited by 199 · see citing works
Analogs of α-Conotoxin MII Are Selective for α6-Containing Nicotinic Acetylcholine Receptors
McIntosh, J. M., Azam, L., Staheli, S. T., Dowell, C. D., Lindstrom, J. M., Kuryatov, A., Garrett, J. E., Marks, M. J., & Whiteaker, P. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.4.944 · Cited by 194 · see citing works
Parker, M. J., Beck, A., & Luetje, C. W. (1998) · PubMed · Cited by 165 · see citing works
Neuronal Nicotinic Receptor β2 and β4 Subunits Confer Large Differences in Agonist Binding Affinity
Parker, M. J., Beck, A., & Luetje, C. W. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.6.1132 · Cited by 161 · see citing works
Azam, L., Dowell, C. D., Watkins, M., Stitzel, J. A., Olivera, B. M., & McIntosh, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406281200 · Cited by 119 · see citing works
Stauderman, K. A., Mahaffy, L. S., AKONG, M., Veliçelebi, G., Chavez-Noriega, L. E., Crona, J. H., Johnson, E. C., Elliott, K. J., Gillespie, A. J., Reid, R. T., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37270-2 · Cited by 90 · see citing works
Slater, Y. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00025-x · Cited by 86 · see citing works
Stauderman, K. A., Mahaffy, L. S., Akong, M., Veliçelebi, G., Chavez-Noriega, L. E., Crona, J. H., Johnson, E. C., Elliott, K. J., Gillespie, A., Reid, R. T., et al. (1998) · PubMed · doi:10.7270/q28g8j7q · Cited by 86 · see citing works
Chavez-Noriega, L. E., Gillespie, A. J., Stauderman, K. A., Crona, J. H., Claeps, B. O., Elliott, K. J., Reid, R. T., Rao, T. S., Veliçelebi, G., Harpold, M. M., et al. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00134-9 · Cited by 73 · see citing works
Coe, J. W., Brooks, P. R., Wirtz, M. C., Bashore, C. G., Bianco, K. E., Vetelino, M. G., Arnold, E. P., Lebel, L. A., Fox, C. B., Tingley, F. D., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.08.035 · Cited by 73 · see citing works
Coe, J. W., Vetelino, M. G., Bashore, C. G., Wirtz, M. C., Brooks, P. R., Arnold, E. P., Lebel, L. A., Fox, C. B., Sands, S. B., Davis, T. I., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.04.036 · Cited by 69 · see citing works
Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes
Carbonnelle, E., Sparatore, F., Canu, C., Salvagno, C., Baldani‐Guerra, B., Terstappen, G. C., Zwart, R., Vijverberg, H. P. M., Clementi, F., & Gotti, C. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01817-x · Cited by 54 · see citing works
Xiao, Y., Baydyuk, M., Wang, H. (., Davis, H. E., & Kellar, K. J. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2003.09.105 · Cited by 36 · see citing works
Avalos, M., Parker, M. J., Maddox, F. N., Carroll, F. I., & Luetje, C. W. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.035899 · Cited by 36 · see citing works
Coe, J. W., Singer, R. A., Brooks, P. R., Caron, S., Ng, K., Vazquez, E., Vetelino, M. G., Watson, H., Whritenour, D. C., & Wirtz, M. C. (2004) · Synthesis · doi:10.1055/s-2004-829135 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Nicotine receptor partial agonists for smoking cessation
Cahill, K., Stead, L., & Lancaster, T. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006103.pub2 · Cited by 747 · see citing works
Systematic integration of biomedical knowledge prioritizes drugs for repurposing
Himmelstein, D. S., Lizee, A., Hessler, C., Brueggeman, L., Chen, S. L., Hadley, D., Green, A., Khankhanian, P., & Baranzini, S. E. (2017) · eLife · doi:10.7554/elife.26726 · Cited by 666 · see citing works
Rollema, H., Chambers, L. K., Coe, J. W., Glowa, J., Hurst, R. S., Lebel, L. A., Lu, Y., Mansbach, R. S., Mather, R. J., Rovetti, C. C., et al. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.10.016 · Cited by 533 · see citing works
PICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 451 · see citing works
Nicotinic ACh receptors as therapeutic targets in CNS disorders
Dineley, K. T., Pandya, A. A., & Yakel, J. L. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.12.002 · Cited by 449 · see citing works
Nicotine receptor partial agonists for smoking cessation
Cahill, K., Lindson-Hawley, N., Thomas, K. H., Fanshawe, T. R., & Lancaster, T. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006103.pub7 · Cited by 433 · see citing works
Steensland, P., Simms, J. A., Holgate, J. Y., Richards, J. K., & Bartlett, S. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705368104 · Cited by 368 · see citing works
2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment
Barua, R. S., Rigotti, N. A., Benowitz, N. L., Cummings, K. M., Jazayeri, M., Morris, P. B., Ratchford, E. V., Sarna, L., Stecker, E. C., & Wiggins, B. S. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.10.027 · Cited by 377 · see citing works
Shi, Y., Weingarten, T. N., Mantilla, C. B., Hooten, W. M., & Warner, D. O. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181ebdaf9 · Cited by 304 · see citing works
Ayers, J. W., Ribisl, K. M., & Brownstein, J. S. (2011) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2010.12.007 · Cited by 298 · see citing works
Litten, R. Z., Ryan, M. L., Fertig, J. B., Falk, D. E., Johnson, B., Dunn, K. E., Green, A. I., Pettinati, H. M., Ciraulo, D. A., Sarid-Segal, O., et al. (2013) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e31829623f4 · Cited by 287 · see citing works
Singh, S., Loke, Y. K., Spangler, J. G., & Furberg, C. D. (2011) · Canadian Medical Association Journal · doi:10.1503/cmaj.110218 · Cited by 286 · see citing works
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur, Y. S., & Picciotto, M. R. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.004 · Cited by 277 · see citing works
The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders
Grayson, D. R., & Guidotti, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.125 · Cited by 267 · see citing works
Jones, C. K., Byun, N. E., & Bubser, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.199 · Cited by 228 · see citing works
Varenicline improves mood and cognition during smoking abstinence
Patterson, F., Jepson, C., Strasser, A. A., Loughead, J., Perkins, K. A., Gur, R. C., Frey, J. M., Siegel, S., & Lerman, C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.028 · Cited by 222 · see citing works
Neuronal nicotinic receptors: A perspective on two decades of drug discovery research
Arneric, S. P., Holladay, M., & Williams, M. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.06.033 · Cited by 208 · see citing works
α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson’s Disease
Quik, M., & Wonnacott, S. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003269 · Cited by 194 · see citing works
Ultrapotent chemogenetics for research and potential clinical applications
Magnus, C. J., Lee, P. H., Bonaventura, J., Zemla, R., Gomez, J. L., Ramirez, M. H., Hu, X., Galván, A., Basu, J., Michaelides, M., et al. (2019) · Science · doi:10.1126/science.aav5282 · Cited by 192 · see citing works
The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function
Sinkus, M. L., Graw, S. L., Freedman, R., Ross, R. G., Lester, H. A., & Leonard, S. S. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.02.006 · Cited by 186 · see citing works
Nicotine receptor partial agonists for smoking cessation
Cahill, K., Stead, L. F., & Lancaster, T. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006103.pub5 · Cited by 187 · see citing works
Nicotine receptor partial agonists for smoking cessation
Cahill, K., Stead, L. F., & Lancaster, T. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006103.pub6 · Cited by 177 · see citing works
Rollema, H., Shrikhande, A., Ward, K., Tingley III, F., Coe, J., O'Neill, B., Tseng, E., Wang, E., Mather, R., Hurst, R., et al. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00682.x · Cited by 162 · see citing works
Smoking cessation and reduction in people with chronic mental illness
Tidey, J. W., & Miller, M. E. (2015) · BMJ · doi:10.1136/bmj.h4065 · Cited by 165 · see citing works
How Can We Use Our Knowledge of Alcohol-Tobacco Interactions to Reduce Alcohol Use?
McKee, S. A., & Weinberger, A. H. (2012) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050212-185549 · Cited by 160 · see citing works
Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential
Romanelli, M. N., Gratteri, P., Guandalini, L., Martini, E., Bonaccini, C., & Gualtieri, F. (2007) · ChemMedChem · doi:10.1002/cmdc.200600207 · Cited by 164 · see citing works
Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers
Benowitz, N. L., Pipe, A., West, R., Hays, J. T., Tonstad, S., McRae, T. D., Lawrence, D., Aubin, L. S., & Anthenelli, R. M. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2018.0397 · Cited by 161 · see citing works
The role of the habenula in drug addiction
Velasquez, K. M., Molfese, D. L., & Salas, R. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00174 · Cited by 155 · see citing works
(−)-Cytisine and Derivatives: Synthesis, Reactivity, and Applications
Rouden, J., Lasne, M., Blanchet, J., & Baudoux, J. (2013) · Chemical Reviews · doi:10.1021/cr400307e · Cited by 149 · see citing works
Hong, L. E. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.83 · Cited by 150 · see citing works
Plebani, J. G., Lynch, K. G., Yu, Q. P., Pettinati, H. M., O’Brien, C. P., & Kampman, K. M. (2012) · Cited by 142 · see citing works
Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice
Aubin, H., Luquiens, A., & Berlin, I. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12116 · Cited by 138 · see citing works
Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125314557797 · Cited by 134 · see citing works
Nicotinic acetylcholine receptors in neuropathic and inflammatory pain
Hone, A. J., & McIntosh, J. M. (2017) · FEBS Letters · doi:10.1002/1873-3468.12884 · Cited by 134 · see citing works
Fowler, C. D., Arends, M. A., & Kenny, P. J. (2008) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32830c360e · Cited by 131 · see citing works
Hendrickson, L. M., Guildford, M. J., & Tapper, A. R. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00029 · Cited by 132 · see citing works
Tuesta, L. M., Fowler, C. D., & Kenny, P. J. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.026 · Cited by 129 · see citing works
Drug targets for cognitive enhancement in neuropsychiatric disorders.
Wallace, T. L., Ballard, T. M., Pouzet, B., Riedel, W. J., & Wettstein, J. G. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.03.022 · Cited by 127 · see citing works
Loughead, J., Ray, R., Wileyto, E. P., Ruparel, K., Sanborn, P. M., Siegel, S. J., Gur, R. C., & Lerman, C. E. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.016 · Cited by 123 · see citing works
Pharmacotherapy of amphetamine-type stimulant dependence: An update
Brensilver, M., Heinzerling, K., & Shoptaw, S. (2013) · Drug and Alcohol Review · doi:10.1111/dar.12048 · Cited by 122 · see citing works
Alpha7 nicotinic receptors as therapeutic targets for Parkinson’s disease
Quik, M., Zhang, D., McGregor, M., & Bordia, T. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.06.014 · Cited by 113 · see citing works
Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy.
Tutka, P., & Zatoński, W. A. (2006) · PubMed · Cited by 123 · see citing works
Neurobiological Mechanisms of Nicotine Reward and Aversion
Wills, L. P., Ables, J. L., Braunscheidel, K. M., Caligiuri, S. P. B., Elayouby, K. S., Fillinger, C., Ishikawa, M., Moen, J. K., & Kenny, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000299 · Cited by 126 · see citing works
Role of CB2 Cannabinoid Receptors in the Rewarding, Reinforcing, and Physical Effects of Nicotine
Navarrete, F., Rodríguez‐Arias, M., Martín‐García, E., Navarro, D., García‐Gutiérrez, M. S., Aguilar, M. A., Aracil-Fernández, A., Berbel, P. J., Miñarro, J., Maldonado, R. J., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.157 · Cited by 121 · see citing works
A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3
Zesiewicz, T. A., Greenstein, P. E., Sullivan, K. L., Wecker, L., Miller, A., Jahan, I., Chen, R., & Perlman, S. (2012) · Neurology · doi:10.1212/wnl.0b013e318247cc7a · Cited by 119 · see citing works
Salim, A. A., Chin, Y., & Kinghorn, A. D. (2008) · Springer eBooks · doi:10.1007/978-3-540-74603-4_1 · Cited by 115 · see citing works
Brunzell, D. H., & McIntosh, J. M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.299 · Cited by 114 · see citing works
Nicotine receptor partial agonists for smoking cessation
Cahill, K., Stead, L. F., & Lancaster, T. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006103.pub3 · Cited by 116 · see citing works
Shim, J.-C., Jung, D.-U., Jung, S. S., Seo, Y.-S., Cho, D.-M., Lee, J.-H., Lee, S.-W., Kong, B.-G., Kang, J.-W., Oh, M., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.238 · Cited by 112 · see citing works
Smith, R. C., Lindenmayer, J., Davis, J. M., Cornwell, J. A., Noth, K., Gupta, S., Sershen, H. W., & Lajtha, Á. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.02.001 · Cited by 107 · see citing works
Ericson, M., Löf, E., Stomberg, R., & Söderpalm, B. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.147058 · Cited by 109 · see citing works
Graef, S., Schönknecht, P., Sabri, O., & Hegerl, U. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2153-8 · Cited by 107 · see citing works
Smoking Behaviour and Mental Health Disorders—Mutual Influences and Implications for Therapy
Minichino, A., Bersani, F. S., Calò, W. K., Spagnoli, F., Francesconi, M., Vicinanza, R., Chiaie, R. D., & Biondi, M. (2013) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph10104790 · Cited by 104 · see citing works
Wirta, D., Vollmer, P. M., Paauw, J. D., Chiu, K.-H., Henry, E., Striffler, K., Nau, J. A., Wirta, D., Rubin, J. M., Reilly, C. D., et al. (2021) · Ophthalmology · doi:10.1016/j.ophtha.2021.11.004 · Cited by 105 · see citing works
Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse
Cross, S. J., Lotfipour, S., & Leslie, F. M. (2016) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2016.1209512 · Cited by 101 · see citing works
Grady, S. R., Drenan, R. M., Breining, S. R., Yohannes, D., Wageman, C. R., Fedorov, N. B., McKinney, S., Whiteaker, P., Bencherif, M., Lester, H. A., et al. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.01.013 · Cited by 98 · see citing works
Wouda, J. A., Riga, D., de Vries, W., Stegeman, M., van Mourik, Y., Schetters, D., Schoffelmeer, A. N. M., Pattij, T., & Vries, T. J. D. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2213-8 · Cited by 99 · see citing works
Kamens, H. M., Andersen, J., & Picciotto, M. R. (2010) · Psychopharmacology · doi:10.1007/s00213-009-1759-1 · Cited by 100 · see citing works
Hendrickson, L. M., Zhao-Shea, R., Pang, X.-Y., Gardner, P. D., & Tapper, A. R. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2601-10.2010 · Cited by 101 · see citing works
Wing, V. C., Wass, C., Soh, D. W., & George, T. P. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06261.x · Cited by 99 · see citing works
Medications for alcohol use disorders: An overview
Akbar, M. D., Egli, M., Cho, Y., Song, B., & Noronha, A. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.11.007 · Cited by 97 · see citing works
Influence of Neuronal Nicotinic Receptors over Nicotine Addiction and Withdrawal
De Biasi, M., & Salas, R. (2008) · Experimental Biology and Medicine · doi:10.3181/0712-mr-355 · Cited by 95 · see citing works
Litten, R. Z., Wilford, B. B., Falk, D. E., Ryan, M. L., & Fertig, J. B. (2016) · Substance Abuse · doi:10.1080/08897077.2015.1133472 · Cited by 94 · see citing works
Quik, M., Perez, X. A., & Grady, S. R. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.001 · Cited by 94 · see citing works
Melis, M., Scheggi, S., Carta, G., Madeddu, C., Lecca, S., Luchicchi, A., Cadeddu, F., Frau, R., Fattore, L., Fadda, P., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4647-12.2013 · Cited by 94 · see citing works
Schmaal, L., Berk, L., Hulstijn, K. P., Cousijn, J., Wiers, R. W., & van den Brink, W. (2011) · European Addiction Research · doi:10.1159/000327682 · Cited by 93 · see citing works
Parikh, V., Kutlu, M. G., & Gould, T. J. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.01.020 · Cited by 95 · see citing works
Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors
Froestl, W., Muhs, A., & Pfeifer, A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121186 · Cited by 91 · see citing works
Trends in Cell-Based Electrochemical Biosensors
Ding, L., Du, D., Zhang, X., & Ju, H. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708786848514 · Cited by 90 · see citing works
Turner, J. R., Castellano, L. M., & Blendy, J. A. (2010) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.166280 · Cited by 88 · see citing works
Varenicline Augmentation in Depressed Smokers: An 8-Week, Open-Label Study
Philip, N. S., Carpenter, L. L., Tyrka, A. R., Whiteley, L. B., & Price, L. H. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08m04441 · Cited by 86 · see citing works
The Duplicated α7 Subunits Assemble and Form Functional Nicotinic Receptors with the Full-length α7
Wang, Y., Xiao, C., Indersmitten, T., Freedman, R., Leonard, S. S., & Lester, H. A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.582858 · Cited by 85 · see citing works
Keever, K. R., Yakubenko, V. P., & Hoover, D. B. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106758 · Cited by 82 · see citing works
Nicotinic acetylcholine receptors: an overview on drug discovery
D’hoedt, D., & Bertrand, D. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220902841045 · Cited by 79 · see citing works
Namba, M. D., Leyrer-Jackson, J. M., Nagy, E. K., Olive, M. F., & Neisewander, J. L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.650785 · Cited by 76 · see citing works
LeSage, M. G., Shelley, D., Ross, J. T., Carroll, F. I., & Corrigall, W. A. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.08.024 · Cited by 78 · see citing works
Nicotinic mechanisms influencing synaptic plasticity in the hippocampus
Placzek, A. N., Zhang, T. A., & Dani, J. A. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.39 · Cited by 77 · see citing works
Salas, R., Main, A., Gangitano, D., & De Biasi, M. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.08.017 · Cited by 76 · see citing works
Tobacco dependence and withdrawal: Science base, challenges and opportunities for pharmacotherapy☆
Henningfield, J. E., Shiffman, S. S., Ferguson, S. G., & Gritz, E. R. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.03.011 · Cited by 76 · see citing works
Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease
McDaid, J., Mustaly-Kalimi, S., & Stutzmann, G. E. (2020) · Cells · doi:10.3390/cells9122655 · Cited by 73 · see citing works
Huang, L. Z., Campos, C., Ly, J., Carroll, F. I., & Quik, M. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.032 · Cited by 73 · see citing works
Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons
Loser, D., Hinojosa, M. G., Blum, J. H., Schaefer, J., Brüll, M., Johansson, Y., Suciu, I., Grillberger, K., Danker, T., Möller, C., et al. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03031-1 · Cited by 75 · see citing works
Jimenez-Ruiz, C. A., Berlin, I., & Hering, T. (2009) · Drugs · doi:10.2165/00003495-200969100-00003 · Cited by 72 · see citing works
Igari, M., Alexander, J. C., Ji, Y. R., Qi, X., Papke, R. L., & Bruijnzeel, A. W. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.216 · Cited by 75 · see citing works
Structure–odour relationships reviewed in the postgenomic era
de March, C. A., Ryu, S., Sicard, G., Moon, C., & Golebiowski, J. (2015) · Flavour and Fragrance Journal · doi:10.1002/ffj.3249 · Cited by 71 · see citing works
Portugal, G. S., & Gould, T. J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.05.006 · Cited by 71 · see citing works
Bordia, T., Hrachova, M., Chin, M., McIntosh, J. M., & Quik, M. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.194852 · Cited by 70 · see citing works
Causal Factors of Increased Smoking in ADHD: A Systematic Review
van Amsterdam, J., van der Velde, B., Schulte, M., & van den Brink, W. (2018) · Substance Use & Misuse · doi:10.1080/10826084.2017.1334066 · Cited by 63 · see citing works
Billen, B., Spurný, R., Brams, M., van Elk, R., Valera-Kummer, S., Yakel, J. L., Voets, T., Bertrand, D., Smit, A. B., & Ulens, C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116397109 · Cited by 69 · see citing works
Varenicline Is a Potent Agonist of the Human 5-Hydroxytryptamine3 Receptor
Lummis, S. C. R., Thompson, A. J., Bencherif, M., & Lester, H. A. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.185306 · Cited by 71 · see citing works
Smith, R. C., Amiaz, R., Si, T., Maayan, L. A., Jin, H., Boules, S., Sershen, H. W., Li, C., Ren, J., Liu, Y., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0143490 · Cited by 79 · see citing works
Feduccia, A. A., Simms, J. A., Mill, D., Yi, H. Y., & Bartlett, S. E. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12690 · Cited by 69 · see citing works
Results of an initial clinical trial of varenicline for the treatment of cocaine dependence
Plebani, J. G., Lynch, K. G., Yu, Q. P., Pettinati, H. M., O’Brien, C. P., & Kampman, K. M. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.08.025 · Cited by 68 · see citing works
Varenicline for smoking cessation: efficacy, safety, and treatment recommendations
Ebbert, J. O. (2010) · Patient Preference and Adherence · doi:10.2147/ppa.s10620 · Cited by 67 · see citing works
Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning
Gould, T. J., & Leach, P. T. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.004 · Cited by 68 · see citing works
The Role of the Habenula in Nicotine Addiction
Baldwin, P. R., Alanis, R., & Salas, R. (2012) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s1-002 · Cited by 67 · see citing works
Gao, B.-X., Hierl, M., Clarkin, K., Juan, T., Nguyen, H. Q., van der Valk, M., Deng, H. X., Guo, W., Lehto, S. G., Matson, D. J., et al. (2010) · Pain · doi:10.1016/j.pain.2010.01.007 · Cited by 67 · see citing works
The Glycine Receptor—A Functionally Important Primary Brain Target of Ethanol
Söderpalm, B., Lidö, H. H., & Ericson, M. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13483 · Cited by 68 · see citing works
Mechanistic insights into nicotine withdrawal
Paolini, M., & De Biasi, M. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.075 · Cited by 66 · see citing works
Nicotine and Nicotinic Receptor Drugs
Quik, M., Bordia, T., Zhang, D., & Perez, X. A. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.07.005 · Cited by 66 · see citing works
- Authors
- Mihalak, K. B., Carroll, F. I., & Luetje, C. W.
- Affiliations
- University of Miami (US)
- RTI International (US)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 70
- Issue
- 3
- Pages
- 801-805
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2141246891
- Cited by
- 558
- References
- 26
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 7 · 2023: 23 · 2022: 14 · 2021: 15 · 2020: 20 · 2019: 19 · 2018: 22 · 2017: 32 · 2016: 41 · 2015: 40 · 2014: 44 · 2013: 48 · 2012: 36
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Miami
- U.S. Food and Drug Administration
- National Heart, Lung, and Blood Institute (T32HL007188)
- National Institute of Mental Health (MH-66038, R01MH066038)
- National Institute on Drug Abuse (R01DA012001, DA12001, DA08102, R01DA008102)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- varenicline, neuronal nicotinic acetylcholine receptors, alpha4beta2 receptor, partial agonists, full agonists, receptor selectivity, smoking cessation, cytisine derivatives
- MeSH terms
- Varenicline, Animals, Benzazepines, Neurons, Oocytes, Quinoxalines, Receptors, Nicotinic, Xenopus laevis, Nicotinic Agonists, Rats, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
