Partial nicotinic acetylcholine (alpha4beta2) agonists as promising new medications for smoking cessation

To review the pharmacology, clinical efficacy and safety of partial agonists of alpha4beta2 nicotinic acetylcholine receptor.

Primary literature and review articles were obtained via a PUBMED search (1988-August 2006) using the key terms smoking cessation, partial agonist alpha4beta2 nicotinic acetylcholine receptor, varenicline, cytisine and SSR591813. Additional studies and abstracts were identified from the bibliographies of reviewed literature.

Studies and review articles related to varenicline, cytisine and the partial agonist alpha4beta2 nicotinic acetylcholine receptor were reviewed.

Smoking is widely recognized as a serious health problem. Smoking cessation has major health benefits. According to the US Public Health Services, all patients attempting to quit smoking should be encouraged to use one or more effective pharmacotherapy. Currently, along with nicotine replacement therapy, bupropion, nortriptyline and clonidine, are the mainstay of pharmacotherapy. More than (3/4) of patients receiving treatment for smoking cessation return to smoking within the first year. Nicotine, through stimulating alpha4beta2 nAChR, releases dopamine in the reward pathway. Partial agonist of alpha4beta2 nAChR elicits moderate and sustained release of dopamine, which is countered during the cessation attempts; it simultaneously blocks the effects of nicotine by binding with alpha4beta2 receptors during smoking. Recently, varenicline, a partial agonist at alpha4beta2 nAChR, has been approved by the FDA (Food and Drug Administration) for smoking cessation.

Partial agonist alpha4beta2 nAChR appears to be a promising target in smoking cessation. Varenicline of this group is approved for treatment of smoking cessation by the FDA in May 2006.