Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.
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.
Department of Medicine, Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, University of California, San Francisco, California 94143-1220, USA. NBenowitz@MedSFGH.ucsf.edu
Neal L
NL
Benowitz
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D001552:Benzazepines / Q000627:therapeutic use; D016642:Bupropion / Q000627:therapeutic use; D005731:Ganglionic Stimulants / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D009538:Nicotine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D004366:Nonprescription Drugs / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D012907:Smoking / Q000009:adverse effects*; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000209:etiology*; D000068580:Varenicline
D001552:Benzazepines; D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D004366:Nonprescription Drugs; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D000068580:Varenicline