Citation

Singh J, Budhiraja S. Indian J. Pharmacol. 2008; 40(5 Suppl): 191-196.

Copyright

(Copyright © 2008, Medknow Publications)

DOI

10.4103/0253-7613.44150

PMID

unavailable

Abstract

OBJECTIVE: To review the pharmacology, clinical efficacy and safety of partial agonists of a4β 2 nicotinic acetylcholine receptor. Data Sources: 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. Study Selection and Data Extraction: Studies and review articles related to varenicline, cytisine and the partial agonist alpha4beta2 nicotinic acetylcholine receptor were reviewed. Data Synthesis: 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 α4β 2 nAChR, releases dopamine in the reward pathway. Partial agonist of α4β 2 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 α4β 2 receptors during smoking. Recently, varenicline, a partial agonist at α4β 2 nAChR, has been approved by the FDA (Food and Drug Administration) for smoking cessation.

CONCLUSION: Partial agonist α4β 2 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.

Language: en

Keywords

human; suicide; suicidal ideation; depression; behavior change; clinical trial; review; Asian; vomiting; drug metabolism; amfebutamone; nortriptyline; unclassified drug; carbon monoxide; sleep disorder; dopamine; constipation; signal transduction; clonidine; nonhuman; drug safety; placebo; food and drug administration; drug efficacy; drug receptor binding; receptor affinity; drug tolerability; nausea; drug withdrawal; nicotine; drug effect; side effect; cimetidine; neurobiology; dopaminergic transmission; withdrawal syndrome; agitation; drug half life; drug approval; reinforcement; drug contraindication; drug elimination; flatulence; reward; drug potency; receptor upregulation; drug indication; drug clearance; smoking cessation; concentration response; limbic system; Smoking cessation; tobacco dependence; drug self administration; unspecified side effect; drug bioavailability; disease model; drug antagonism; nerve cell plasticity; mecamylamine; cytosine derivative; molecular mechanics; varenicline; nicotine replacement therapy; nerve conduction; maximum plasma concentration; cytisine; nicotinic agent; Varenicline; dopamine release; drug discrimination; nicotinic receptor; 2 methyl 3 (2 pyrrolidinylmethoxy)pyridine; Cytisine; ispronicline; long term potentiation; neurotransmitter release; nicotinic receptor alpha4beta2; partial agonist; Partial agonist α4β 2 nAChR; ssr 591813; SSR591813; sustained release preparation; tc 2559; turnover time