Cited by 979Smoking Behavior and CessationNicotinic Acetylcholine Receptors StudySubstance Abuse Treatment and Outcomes

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Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics

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Benowitz, Neal L.·2009·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev.pharmtox.48.113006.094742PMC PMC2946180

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Abstract

Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.

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Authors: Benowitz, N. L.
Affiliations: San Francisco General Hospital (US)
Corresponding author: Benowitz, Neal L.
ORCID: Benowitz, Neal L.
Venue: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
Published: 2009-02-01
Volume: 49
Issue: 1
Pages: 57-71
ISSN: 0362-1642 (ISSN-L)
1545-4304
DOI: 10.1146/annurev.pharmtox.48.113006.094742
PMC: PMC2946180
OpenAlex: W2137599927
Cited by: 979
References: 90
Citations by year: 2026: 75 · 2025: 89 · 2024: 91 · 2023: 89 · 2022: 72 · 2021: 70 · 2020: 60 · 2019: 56 · 2018: 42 · 2017: 55 · 2016: 37 · 2015: 42 · 2014: 43 · 2013: 39 · 2012: 35
FWCI: 2.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Annual Review of Pharmacology and Toxicology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Public Health Service
National Institute on Drug Abuse (DA20830, DA02277, R01DA002277, U01DA020830, R37DA002277)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: nicotine, tobacco dependence, nicotine dependence, nicotinic acetylcholine receptors, nicotine withdrawal, dopamine release, glutamate release, GABA release, corticotropin-releasing factor, genetic susceptibility, CYP2A6, nicotine metabolism, lung cancer risk, smoking cessation, mental illness, substance abuse, nicotine replacement therapy, bupropion, varenicline, partial agonists
MeSH terms: Varenicline, Animals, Benzazepines, Nonprescription Drugs, Ganglionic Stimulants, Humans, Nicotine, Quinoxalines, Smoking, Tobacco Use Disorder, Bupropion, Behavior, Addictive, Nicotinic Agonists

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