ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
A single administration of low-dose varenicline saturates α4β2* nicotinic acetylcholine receptors in the human brain.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Tobacco smoking and dopaminergic function in humans: a meta-analysis of molecular imaging studies.Psychopharmacology · 2019Pooled it
- Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials.BMC public health · 2015Pooled it
- Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial.Drug and alcohol dependence · 2021Trial
- The Relationship of Varenicline Agonism of α4β2 Nicotinic Acetylcholine Receptors and Nicotine-Induced Dopamine Release in Nicotine-Dependent Humans.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Trial
- Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals.Psychopharmacology · 2014Trial
- α4β2Annals of neurology · 2021Article
- Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Evaluation of (-)-[Synapse (New York, N.Y.) · 2018Article
- Venom based neural modulators.Experimental and therapeutic medicine · 2018Article
- Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.Journal of neurochemistry · 2017Article
- Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors.Current topics in medicinal chemistry · 2016Review
- Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015Article
- α2-Null mutant mice have altered levels of neuronal activity in restricted midbrain and limbic brain regions during nicotine withdrawal as demonstrated by cfos expression.Biochemical pharmacology · 2015Article
- Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors.Journal of medicinal chemistry · 2014Review
- Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans.Neuropharmacology · 2014Review
- Varenicline is a potent partial agonist at α6β2* nicotinic acetylcholine receptors in rat and monkey striatum.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The primary objective of this project was to determine the α4β2(*) nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms ((*)denoting other putative nAChR subunits). Otherwise healthy smokers (n=9) underwent two positron emission tomography (PET) sessions with the selective α4β2(*) radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K(V)), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of α4β2(*) nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K(V) with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of α4β2(*) nAChRs in the thalamus and brainstem without reducing withdrawal symptoms.
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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.