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GABAA受体亚型:对苯二氮䓬类药物依赖机制有何线索?

GABAA receptor subtypes: any clues to the mechanism of benzodiazepine dependence?

作者信息

Wafford Keith A

机构信息

Department of Molecular and Cellular Neuroscience, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex CM20 2QR, UK.

出版信息

Curr Opin Pharmacol. 2005 Feb;5(1):47-52. doi: 10.1016/j.coph.2004.08.006.

Abstract

Chronic use of benzodiazepines for the treatment of anxiety has revealed that these drugs can lead to dependence as indicated by withdrawal symptoms following cessation and tolerance to the drugs effects. Together with their reinforcing properties, this has led to them being labelled as scheduled drugs. Our new knowledge regarding the molecular structure of the benzodiazepine binding site and the growing ability to differentiate GABA(A) receptor subtypes, either by genetic manipulation or subtype selective compounds, have begun to facilitate our understanding of what underlies the mechanism of benzodiazepine dependence. In addition, the involvement of GABA(A) receptors in this phenomenon is leading to a greater understanding of other drugs such as alcohol and opiates.

摘要

长期使用苯二氮䓬类药物治疗焦虑症已表明,这些药物会导致药物依赖,如停药后的戒断症状以及对药物作用产生耐受性所示。再加上它们的强化特性,这使得它们被列为管制药物。我们关于苯二氮䓬类药物结合位点分子结构的新知识,以及通过基因操作或亚型选择性化合物区分GABA(A)受体亚型的能力不断提高,已开始促进我们对苯二氮䓬类药物依赖机制的理解。此外,GABA(A)受体在这一现象中的作用,正使人们对酒精和阿片类等其他药物有了更深入的了解。

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