Preclinical pharmacology of the α4β2 nAChR partial agonist varenicline related to effects on reward, mood and cognition
Preclinical pharmacology of the α4β2 nAChR partial agonist varenicline related to effects on reward, mood and cognition
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DOI：
10.1016/j.bcp.2009.05.033
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发表时间：
2009-10-01
影响因子：
5.8
通讯作者：
Williams, Kathryn E.
中科院分区：
文献类型：
--
作者：
Rollema, Hans;Hajos, Mihaly;Williams, Kathryn E.
α 4 β 2烟碱乙酰胆碱受体（nAChR）部分激动剂伐尼克兰的药理学性质和药代动力学特征提供了游离脑水平和靶受体功能效力的有利组合，这在很大程度上解释了其作为戒烟辅助剂的功效。由于α 4 β 2和其他nAChR亚型在介导控制奖赏、情绪、认知和注意力的中枢过程中发挥重要作用，因此有兴趣在评估这些行为的临床前动物模型中检查选择性nAChR配体如伐尼克兰的作用。在这里，我们描述的结果从研究的varenicline的成瘾，抑郁，认知和注意力的动物模型的影响，并讨论这些在最近发表的临床前和初步临床研究的背景下，收集数据varenicline的情绪，认知和酒精滥用障碍的影响。总之，临床前和有限的临床数据显示伐尼克兰的有益作用，但需要进一步的临床研究来评估在动物模型中观察到的临床前作用是否可转化为临床。(C)2009 Elsevier Inc. All rights reserved.
The pharmacological properties and pharmacokinetic profile of the alpha 4 beta 2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline provide an advantageous combination of free brain levels and functional potencies at the target receptor that for a large part explain its efficacy as a smoking cessation aid. Since alpha 4 beta 2 and other nAChR subtypes play important roles in mediating central processes that control reward, mood, cognition and attention, there is interest in examining the effects of selective nAChR ligands such as varenicline in preclinical animal models that assess these behaviors. Here we describe results from studies on varenicline's effects in animal models of addiction, depression, cognition and attention and discuss these in the context of recently published preclinical and preliminary clinical studies that collected data on varenicline's effects on mood, cognition and alcohol abuse disorder. Taken together, the preclinical and the limited clinical data show beneficial effects of varenicline, but further clinical studies are needed to evaluate whether the preclinical effects observed in animal models are translatable to the clinic. (C) 2009 Elsevier Inc. All rights reserved.