Department of Pharmacology, Pt. B. D. Sharma PGIMS, Haryana, India.
Indian J Pharmacol. 2008 Oct;40(5):191-6. doi: 10.4103/0253-7613.44150.
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.
综述α4β2 型烟碱型乙酰胆碱受体部分激动剂的药理学、临床疗效和安全性。
通过 PUBMED 检索（1988 年 8 月-2006 年），使用“戒烟、α4β2 型烟碱型乙酰胆碱受体部分激动剂、伐仑克林、烟碱和 SSR591813”等关键词，查找主要文献和综述文章。还从已审阅文献的参考文献中查找了其他研究和摘要。
对伐仑克林、烟碱和α4β2 型烟碱型乙酰胆碱受体部分激动剂的相关研究和综述文章进行了评估。
吸烟是公认的严重健康问题。戒烟对健康有重大益处。根据美国公共卫生署的建议，所有尝试戒烟的患者都应被鼓励使用一种或多种有效的药物治疗。目前，除尼古丁替代疗法、安非他酮、去甲替林和可乐定外，bupropion、 nortriptyline 和 clonidine 也是药物治疗的主要方法。在接受戒烟治疗的患者中，超过 3/4 的人在一年内重新吸烟。尼古丁通过刺激α4β2 nAChR，在奖励途径中释放多巴胺。α4β2 nAChR 的部分激动剂引起中等且持续的多巴胺释放，这种释放在戒烟尝试中被抵消；同时，通过与吸烟期间的α4β2 受体结合，阻断尼古丁的作用。最近，FDA（美国食品和药物管理局）批准了伐仑克林（一种α4β2 nAChR 的部分激动剂）用于戒烟。
α4β2 nAChR 的部分激动剂似乎是戒烟治疗的一个有前途的靶点。伐仑克林作为该类药物的代表，已于 2006 年 5 月被 FDA 批准用于治疗吸烟。
