The DOI matches its Crossref record; 42 of the 44 references it cites were found in a registry or an index.
Pharmacological profile of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid
Abstract
The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment.
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In the citing paper
“neither patch (Jorenby et al., 1995) nor varenicline are reinforcing (Rollema et al., 2007).”
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 Rollema et al., 2007
In the citing paper
“Varenicline, the most effective medication for smoking cessation currently available (Chantix; Pfizer), is a potent partial agonist for a4b2 nAChRs, as well as a weak partial agonist at a3b4 nAChRs and a full agonist at a7 nAChRs (Coe et al, 2005; Rollema et al, 2007).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Rollema et al, 2007
In the citing paper
“Varenicline, the most effective medication for smoking cessation currently available (Chantix; Pfizer), is a potent partial agonist for a4b2 nAChRs, as well as a weak partial agonist at a3b4 nAChRs and a full agonist at a7 nAChRs (Coe et al, 2005; Rollema et al, 2007).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Rollema et al, 2007
In the citing paper
“Varenicline, the most effective medication for smoking cessation currently available (Chantix; Pfizer), is a potent partial agonist for a4b2 nAChRs, as well as a weak partial agonist at a3b4 nAChRs and a full agonist at a7 nAChRs (Coe et al, 2005; Rollema et al, 2007).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Rollema et al, 2007
In the citing paper
“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 Rollema et al., 2007
In the citing paper
“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 Rollema et al., 2007
In the citing paper
“Although the K i values for sazetidine-A and varenicline at ␣42 nAChRs are very similar (0.4 and 0.2 nM, respectively) (Xiao 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 Rollema et al., 2007
In the citing paper
“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 Rollema et al., 2007
In the citing paper
“Although varenicline, like cytisine, is a potent and selective ␣42 partial agonist (Rollema et al., 2007)”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Rollema et al., 2007
In the citing paper
“Varenicline has at least 100-fold higher affinity for α4β2 than for other subtypes, is a 45% agonist as compared with nicotine and can potently desensitize α4β2 nicotinic acetylcholine receptors with an IC50 value of 6 nM for inhibiting nicotine-evoked currents (Rollema et al., 2007).”
From Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect (2009) · cites this paper as Rollema et al., 2007
In the citing paper
“The fact that low doses of varenicline (i.e. 0.25 mg/kg in C57BL/6J mice and 0.178 mg/kg in CD-1 mice) have significant effects in both experiments is consistent with varenicline’s high in vitro binding affinity (Ki = 0.15 nM) and inactivating potency (IC50 = 6 nM) at α4β2 nicotinic acetylcholine receptors, as well as with its potent activity in in vivo models, such as increasing mesolimbic”
From Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect (2009) · cites this paper as Rollema et al., 2007
In the citing paper
“Varenicline has at least 100-fold higher affinity for α4β2 than for other subtypes, is a 45% agonist as compared with nicotine and can potently desensitize α4β2 nicotinic acetylcholine receptors with an IC50 value of 6 nM for inhibiting nicotine-evoked currents (Rollema et al., 2007).”
From Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect (2009) · cites this paper as Rollema et al., 2007
In the citing paper
“Varenicline has at least 100-fold higher affinity for α4β2 than for other subtypes, is a 45% agonist as compared with nicotine and can potently desensitize α4β2 nicotinic acetylcholine receptors with an IC50 value of 6 nM for inhibiting nicotine-evoked currents (Rollema et al., 2007).”
From Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect (2009) · cites this paper as Rollema et al., 2007
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Metadata
- Authors
- 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., Sands, S. B., Schaeffer, E., Schulz, D. W., Tingley, F. D., & Williams, K. E.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Rollema, H.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 52
- Issue
- 3
- Pages
- 985-994
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2101520329
- Cited by
- 533
- References
- 44
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 13 · 2022: 16 · 2021: 19 · 2020: 27 · 2019: 25 · 2018: 27 · 2017: 20 · 2016: 27 · 2015: 37 · 2014: 34 · 2013: 34 · 2012: 41
- FWCI
- 13.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- varenicline, α4β2 nicotinic acetylcholine receptor, partial agonism, smoking cessation, nicotine self-administration, dopamine release, nucleus accumbens, receptor binding affinity
- MeSH terms
- Varenicline, Animals, Behavior, Animal, Benzazepines, Brain, Cell Line, Transformed, Dopamine, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Male, Membrane Potentials, Nicotine, Protein Binding, Quinoxalines, Self Administration, Transfection, Smoking Cessation, Rats, Sprague-Dawley, Patch-Clamp Techniques, Nicotinic Agonists, Rats, Long-Evans, Rats, In Vitro Techniques
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