ArticleMolecular pharmacology2015
Menthol Enhances the Desensitization of Human α3β4 Nicotinic Acetylcholine Receptors.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.Journal of psychopharmacology (Oxford, England) · 2018Trial
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Chemosensory tobacco product toxicology part 2: toxicological testing, assays, and state of the science.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- A multi-year characterization of confiscated vaping products from Virginia school youth.Journal of analytical toxicology · 2024Article
- Investigating the role of nicotinic acetylcholine receptors in menthol's effects in mice.Drug and alcohol dependence · 2024Article
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Chemosensory Contributions of E-Cigarette Additives on Nicotine Use.Frontiers in neuroscience · 2022Review
- Multi-omics insights into the biological mechanisms underlying statistical gene-by-lifestyle interactions with smoking and alcohol consumption.Frontiers in genetics · 2022Article
- Synthesis, Antifungal Activity, 3D-QSAR, and Molecular Docking Study of Novel Menthol-Derived 1,2,4-Triazole-thioether Compounds.Molecules (Basel, Switzerland) · 2021Article
- Differences in Cognitive Task Performance, Reinforcement Enhancement, and Nicotine Dependence Between Menthol and Nonmenthol Cigarette Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021Article
- Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior.Molecules (Basel, Switzerland) · 2021Article
- Tobacco and Nervous System Development and Function-New Findings 2015-2020.Brain sciences · 2021Review
- Article
- A Retrospective Analysis of Chemical Constituents in Regulated and Unregulated E-Cigarette Liquids.Frontiers in chemistry · 2021Article
- Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences.Neuropharmacology · 2020Article
- The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors.Molecules (Basel, Switzerland) · 2020Review
- Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice.Scientific reports · 2020Article
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- Monoterpenes Differently Regulate Acid-Sensitive and Mechano-Gated KFrontiers in pharmacology · 2020Article
- Effect of menthol on nicotine intake and relapse vulnerability in a rat model of concurrent intravenous menthol/nicotine self-administration.Psychopharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The α3β4 nicotinic acetylcholine receptor (nAChR) subtype is widely expressed in the peripheral and central nervous systems, including in airway sensory nerves. The nAChR subtype transduces the irritant effects of nicotine in tobacco smoke and, in certain brain areas, may be involved in nicotine addiction and/or withdrawal. Menthol, a widely used additive in cigarettes, is a potential analgesic and/or counterirritant at sensory nerves and may also influence nicotine's actions in the brain. We examined menthol's effects on recombinant human α3β4 nAChRs and native nAChRs in mouse sensory neurons. Menthol markedly decreased nAChR activity as assessed by Ca(2+) imaging, (86)Rb(+) efflux, and voltage-clamp measurements. Coapplication of menthol with acetylcholine or nicotine increased desensitization, demonstrated by an increase in the rate and magnitude of the current decay and a reduction of the current integral. These effects increased with agonist concentration. Pretreatment with menthol followed by its washout did not affect agonist-induced desensitization, suggesting that menthol must be present during the application of agonist to augment desensitization. Notably, menthol acted in a voltage-independent manner and reduced the mean open time of single channels without affecting their conductance, arguing against a simple channel-blocking effect. Further, menthol slowed or prevented the recovery of nAChRs from desensitization, indicating that it probably stabilizes a desensitized state. Moreover, menthol at concentrations up to 1 mM did not compete for the orthosteric nAChR binding site labeled by [(3)H]epibatidine. Taken together, these data indicate that menthol promotes desensitization of α3β4 nAChRs by an allosteric action.
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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.