ArticleThe Journal of pharmacology and experimental therapeutics2012
Varenicline is a potent partial agonist at α6β2* nicotinic acetylcholine receptors in rat and monkey striatum.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Efficacy and safety of varenicline nasal spray in dry eye disease: a systematic review and meta-analysis of randomized controlled trials.International ophthalmology · 2026Pooled it
- Efficacy of combined varenicline and nicotine replacement therapy compared with varenicline or nicotine replacement therapy alone for smoking cessation: A systematic review and meta-analysis.Addiction (Abingdon, England) · 2026Pooled it
- The role of nicotinic receptors in alcohol consumption.Pharmacological research · 2023Pooled it
- Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease in Sjogren's Disease: A Pilot Study.Clinical ophthalmology (Auckland, N.Z.) · 2025Trial
- Safety, adherence and discontinuation in varenicline solution nasal spray clinical trials for dry eye disease.Journal of comparative effectiveness research · 2023Trial
- Effect of varenicline on major adverse liver outcomes in alcohol-associated liver disease: An exploratory analysis.Alcohol, clinical & experimental research · 2025Article
- "Unraveling the role ofReceptors (Basel, Switzerland) · 2025Article
- Personalized and adaptive interventions for smoking cessation: Emerging trends and determinants of efficacy.iScience · 2024Review
- Administration of Nicotine Can Inhibit Myopic Growth in Animal Models.Investigative ophthalmology & visual science · 2024Article
- Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus.The European journal of neuroscience · 2024Article
- Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.The Lancet regional health. Western Pacific · 2024Article
- Interaction of Varenicline with Classic Antiseizure Medications in the Mouse Maximal Electroshock-Induced Seizure Model.International journal of molecular sciences · 2023Article
- Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Addiction-related neuroadaptations following chronic nicotine exposure.Journal of neurochemistry · 2021Review
- Effect of Varenicline on Tardive Dyskinesia: A Pilot Study.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2021Article
- Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine-A.Addiction biology · 2021Article
- Recent Advances in the Pharmacology of Tardive Dyskinesia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2020Review
- Neuronal nicotinic acetylcholine receptors mediate ∆Addiction biology · 2020Article
- Discriminative Stimulus and Low Abuse Liability Effects of Novel Endomorphin Analogs Suggest a Potential Treatment Indication for Opioid Use Disorder.The Journal of pharmacology and experimental therapeutics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Extensive evidence indicates that varenicline reduces nicotine craving and withdrawal symptoms by modulating dopaminergic function at α4β2* nicotinic acetylcholine receptors (nAChRs) (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex). More recent data suggest that α6β2* nAChRs also regulate dopamine release and mediate nicotine reinforcement. The present experiments were therefore done to test the effect of varenicline on α6β2* nAChRs and their function, because its interaction with this subtype is currently unclear. Receptor competition studies showed that varenicline inhibited α6β2* nAChR binding (K(i) = 0.12 nM) as potently as α4β2* nAChR binding (K(i) = 0.14 nM) in rat striatal sections and with ∼20-fold greater affinity than nicotine. Functionally, varenicline was more potent in stimulating α6β2* versus α4β2* nAChR-mediated [(3)H]dopamine release from rat striatal synaptosomes with EC(50) values of 0.007 and 0.086 μM, respectively. However, it acted as a partial agonist on α6β2* and α4β2* nAChR-mediated [(3)H]dopamine release with maximal efficacies of 49 and 24%, respectively, compared with nicotine. We also evaluated varenicline's action in striatum of monkeys, a useful animal model for comparison with humans. Varenicline again potently inhibited monkey striatal α6β2* (K(i) = 0.13 nM) and α4β2* (K(i) = 0.19 nM) nAChRs in competition studies. Functionally, it potently stimulated both α6β2* (EC(50) = 0.014 μM) and α4β2* (EC(50) = 0.029 μM) nAChR-mediated [(3)H]dopamine release from monkey striatal synaptosomes, again acting as a partial agonist relative to nicotine at both subtypes. These data suggest that the ability of varenicline to interact at α6β2* nAChRs may contribute to its efficacy as a smoking cessation aid.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.