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Review ArticleReview Article

More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder

M. J. Moerke, L. R. McMahon and J. L. Wilkerson
Michael A. Nader, ASSOCIATE EDITOR
Pharmacological Reviews April 2020, 72 (2) 527-557; DOI: https://doi.org/10.1124/pr.119.018028
M. J. Moerke
Division of Preclinical Pharmacology, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (M.J.M.) and Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida (L.R.M., J.L.W.)
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  • For correspondence: megan.moerke@nih.gov
L. R. McMahon
Division of Preclinical Pharmacology, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (M.J.M.) and Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida (L.R.M., J.L.W.)
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J. L. Wilkerson
Division of Preclinical Pharmacology, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (M.J.M.) and Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida (L.R.M., J.L.W.)
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  • For correspondence: jenny.wilkerson@cop.ufl.edu
Michael A. Nader
Roles: ASSOCIATE EDITOR
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Abstract

Tobacco use is a persistent public health issue. It kills up to half its users and is the cause of nearly 90% of all lung cancers. The main psychoactive component of tobacco is nicotine, primarily responsible for its abuse-related effects. Accordingly, most pharmacotherapies for smoking cessation target nicotinic acetylcholine receptors (nAChRs), nicotine’s major site of action in the brain. The goal of the current review is twofold: first, to provide a brief overview of the most commonly used behavioral procedures for evaluating smoking cessation pharmacotherapies and an introduction to pharmacokinetic and pharmacodynamic properties of nicotine important for consideration in the development of new pharmacotherapies; and second, to discuss current and potential future pharmacological interventions aimed at decreasing tobacco use. Attention will focus on the potential for allosteric modulators of nAChRs to offer an improvement over currently approved pharmacotherapies. Additionally, given increasing public concern for the potential health consequences of using electronic nicotine delivery systems, which allow users to inhale aerosolized solutions as an alternative to smoking tobacco, an effort will be made throughout this review to address the implications of this relatively new form of nicotine delivery, specifically as it relates to smoking cessation.

Significance Statement Despite decades of research that have vastly improved our understanding of nicotine and its effects on the body, only a handful of pharmacotherapies have been successfully developed for use in smoking cessation. Thus, investigation of alternative pharmacological strategies for treating tobacco use disorder remains active; allosteric modulators of nicotinic acetylcholine receptors represent one class of compounds currently under development for this purpose.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants R01 DA25267 and UG3 DA48353].

  • https://doi.org/10.1124/pr.119.018028.

  • U.S. Government work not protected by U.S. copyright
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In this issue

Pharmacological Reviews: 72 (2)
Pharmacological Reviews
Vol. 72, Issue 2
1 Apr 2020
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Review ArticleReview Article

Pharmacotherapies for Tobacco Use Disorder

M. J. Moerke, L. R. McMahon and J. L. Wilkerson
Pharmacological Reviews April 1, 2020, 72 (2) 527-557; DOI: https://doi.org/10.1124/pr.119.018028

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Review ArticleReview Article

Pharmacotherapies for Tobacco Use Disorder

M. J. Moerke, L. R. McMahon and J. L. Wilkerson
Pharmacological Reviews April 1, 2020, 72 (2) 527-557; DOI: https://doi.org/10.1124/pr.119.018028
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  • Article
    • Abstract
    • I. Introduction
    • II. Preclinical Methods for Evaluating Potential Pharmacotherapies
    • III. Pharmacokinetic Considerations for Evaluating Potential Pharmacotherapies
    • IV. Pharmacodynamic Considerations for Evaluating Potential Pharmacotherapies
    • V. U.S. Food and Drug Administration–Approved Pharmacotherapies for Smoking Cessation
    • VI. Experimental Pharmacotherapies for Smoking Cessation
    • VII. Conclusion
    • Acknowledgments
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