Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics

Annu Rev Pharmacol Toxicol. 2009:49:57-71. doi: 10.1146/annurev.pharmtox.48.113006.094742.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Behavior, Addictive / chemically induced*
  • Behavior, Addictive / drug therapy*
  • Behavior, Addictive / genetics
  • Benzazepines / therapeutic use
  • Bupropion / therapeutic use
  • Ganglionic Stimulants / chemistry
  • Ganglionic Stimulants / metabolism
  • Ganglionic Stimulants / pharmacokinetics
  • Ganglionic Stimulants / toxicity*
  • Humans
  • Nicotine / chemistry
  • Nicotine / metabolism
  • Nicotine / pharmacokinetics
  • Nicotine / toxicity*
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / metabolism
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Agonists / toxicity*
  • Nonprescription Drugs / therapeutic use
  • Quinoxalines / therapeutic use
  • Smoking / adverse effects*
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / etiology*
  • Varenicline


  • Benzazepines
  • Ganglionic Stimulants
  • Nicotinic Agonists
  • Nonprescription Drugs
  • Quinoxalines
  • Bupropion
  • Nicotine
  • Varenicline