α2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders.
α2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders.
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DOI：
10.1016/j.pharmthera.2012.08.006
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发表时间：
2012-11
影响因子：
13.5
通讯作者：
Rudolph, Uwe
中科院分区：
文献类型：
--
作者：
Engin, Elif;Liu, Jing;Rudolph, Uwe
GABAA受体具有重要的生理功能，药理学研究和基因靶向小鼠模型实验表明，GABAA受体是苯二氮类药物等广泛使用的药物的靶标。在这篇综述中，我们总结了目前关于含有α2受体的功能的知识，这是一种受体亚型，约占所有GABA受体的15-20%。该受体亚型介导地西潘的抗焦虑、增强奖赏和抗痛觉过敏作用，并具有抗抑郁药样特性。继发性α-2受体缺陷在精神分裂症的发病机制中起一定作用，并可能参与其他疾病的认知功能障碍。此外，编码GABAA受体α2亚单位的GABRA2基因的多态已被发现与慢性酒精依赖和多药滥用有关。因此，α-2受体参与情绪行为和慢性疼痛的调节和/或调节，是治疗焦虑、抑郁、精神分裂症和慢性疼痛的有效靶点。
GABAA receptors have important physiological functions, as revealed by pharmacological studies and experiments involving gene-targeted mouse models, and are the target of widely used drugs such as the benzodiazepines. In this review, we are summarizing current knowledge about the function of α2-containing GABAA receptors, a receptor subtype representing approximately 15–20% of all GABAA receptors. This receptor subtype mediates anxiolytic-like, reward-enhancing, and antihyperalgesic actions of diazepam, and has antidepressant-like properties. Secondary insufficiency of α2-containing GABAA receptors has been postulated to play a role in the pathogenesis of schizophrenia, and may be involved in cognitive impairment in other disorders. Moreover, polymorphisms in the GABRA2 gene encoding the GABAA receptor α2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse. Thus, α2-containing GABAA receptors are involved in the regulation and/or modulation of emotional behaviors and of chronic pain, and appear to be a valid target for novel therapeutic approaches for the treatment of anxiety, depression, schizophrenia and chronic pain.
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DOI：
10.1038/npp.2008.171
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
5.3
作者：
Earnheart, John C.;Schweizer, Claude;Luscher, Bernhard
通讯作者：
Luscher, Bernhard
影响因子：
6
作者：
Agrawal, Arpana;Pergadia, Michele L.;Madden, Pamela A. F.
通讯作者：
Madden, Pamela A. F.
影响因子：
10.6
作者：
Enoch, Mary-Anne;Hodgkinson, Colin A.;Yuan, Qiaoping;Shen, Pei-Hong;Goldman, David;Roy, Alec
通讯作者：
Roy, Alec