Nicotinic receptor-based therapeutics and candidates for smoking cessation

Linda P. Dwoskin, Andrew M. Smith, Thomas E. Wooters, Zhenfa Zhang, Peter A. Crooks, Michael T. Bardo

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


Tobacco dependence is the most preventable cause of death and is a chronic, relapsing disorder in which compulsive tobacco use persists despite known negative health consequences. All currently available cessation agents (nicotine, varenicline and bupropion) have limited efficacy and are associated with high relapse rates, revealing a need for more efficacious, alternative pharmacotherapies. The major alkaloid in tobacco, nicotine, activates nicotinic receptors (nAChRs) which increase brain extracellular dopamine producing nicotine reward leading to addiction. nAChRs are located primarily presynaptically and modulate synaptic activity by regulating neurotransmitter release. Subtype-selective nAChR antagonists that block reward-relevant mesocorticolimbic and nigrostriatal dopamine release induced by nicotine may offer advantages over current therapies. An innovative approach is to provide pharmacotherapies which are antagonists at nAChR subtypes mediating nicotine evoked dopamine release. In addition, providing multiple medications with a wider array of targets and mechanisms should provide more treatment options for individuals who are not responsive to the currently available pharmacotherapies. This review summarizes the currently available smoking cessation therapies and discusses emerging potential therapeutic approaches employing pharmacological agents which act as antagonists at nicotinic receptors.

Original languageEnglish
Pages (from-to)732-743
Number of pages12
JournalBiochemical Pharmacology
Issue number7
StatePublished - Oct 1 2009

Bibliographical note

Funding Information:
The research reported in this review was supported by NIH grant U19 DA17548, T32 DA007304 and F31 DA023853.


  • Nicotine
  • Nicotinic acetylcholine receptor
  • Pharmacotherapies
  • Smoking cessation

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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