Cited by 960Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationAlkaloids: synthesis and pharmacology

Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation

Coe, Jotham W., Brooks, Paige R., Vetelino, Michael G., Wirtz, Michael C., Arnold, Eric P., Huang, Jianhua, Sands, Steven B., Davis, Thomas I. +13 more·2005·Journal of Medicinal Chemistry

Abstract

Herein we describe a novel series of compounds from which varenicline (1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine) has been identified for smoking cessation. Neuronal nicotinic acetylcholine receptors (nAChRs) mediate the dependence-producing effects of nicotine. We have pursued alpha4beta2 nicotinic receptor partial agonists to inhibit dopaminergic activation produced by smoking while simultaneously providing relief from the craving and withdrawal syndrome that accompanies cessation attempts. Varenicline displays high alpha4beta2 nAChR affinity and the desired in vivo dopaminergic profile.

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Crossref · 10.1021/jm050069n

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Authors
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., Shrikhande, A., Heym, J. H., Schaeffer, E., Rollema, H., Lu, Y., Mansbach, R. S., Chambers, L. K., Rovetti, C. C., Schulz, D. W., Tingley, F. D., & O'Neill, B. T.
Affiliations
  • Pfizer (United States) (US)
  • Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340
Corresponding author
Coe, Jotham W.
Venue
Journal of Medicinal Chemistry
Published
2005-04-23
Volume
48
Issue
10
Pages
3474-3477
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W1993112595
Cited by
930
References
71
Citations by year
2026: 12 · 2025: 16 · 2024: 26 · 2023: 29 · 2022: 26 · 2021: 29 · 2020: 35 · 2019: 34 · 2018: 30 · 2017: 32 · 2016: 44 · 2015: 54 · 2014: 62 · 2013: 65 · 2012: 70
FWCI
21.84
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
Keywords
varenicline, smoking cessation, α4β2 nicotinic acetylcholine receptor, partial agonists, nicotine dependence, dopamine, nicotine craving, withdrawal syndrome
MeSH terms
Varenicline, Animals, Benzazepines, Cell Line, Cerebral Cortex, Humans, Oocytes, Quinoxalines, Radioligand Assay, Receptors, Nicotinic, Xenopus laevis, Smoking Cessation, Nicotinic Agonists, Rats, In Vitro Techniques

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