基于γ-氨基丁酸的治疗方法：γ-氨基丁酸A型受体亚型的功能

GABA-based therapeutic approaches: GABAA receptor subtype functions.

作者信息

Rudolph Uwe, Möhler Hanns

机构信息

Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland, and Laboratory of Genetic Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.

出版信息

Curr Opin Pharmacol. 2006 Feb;6(1):18-23. doi: 10.1016/j.coph.2005.10.003. Epub 2005 Dec 22.

DOI:10.1016/j.coph.2005.10.003

PMID:16376150

Abstract

It is increasingly being appreciated that GABAA receptor subtypes, through their specific regional, cellular and subcellular localization, are linked to distinct neuronal circuits and consequently serve distinct functions. GABAA receptor subtype-selective drugs are therefore expected to provide novel pharmacological profiles. Receptors containing the alpha1 subunit mediate sedation and serve as targets for sedative hypnotics. Agonists selective for alpha2- and/or alpha3-containing GABAA receptors have been shown to provide anxiolysis without sedation in preclinical models, whereas inverse agonists selective for alpha5-containing GABAA receptors provide memory enhancement. Agonists selective for alpha3-containing GABAA receptors might be suitable for the treatment of deficits in sensorimotor processing in psychiatric disorders. Thus, a new pharmacology based on GABAA receptor subtype-specific actions is emerging.

摘要

人们越来越认识到，GABAA受体亚型通过其特定的区域、细胞和亚细胞定位，与不同的神经回路相连，从而发挥不同的功能。因此，GABAA受体亚型选择性药物有望提供新的药理学特性。含有α1亚基的受体介导镇静作用，并作为镇静催眠药的靶点。在临床前模型中，对含有α2和/或α3的GABAA受体具有选择性的激动剂已被证明可提供抗焦虑作用而无镇静作用，而对含有α5的GABAA受体具有选择性的反向激动剂可增强记忆。对含有α3的GABAA受体具有选择性的激动剂可能适用于治疗精神疾病中感觉运动处理缺陷。因此，一种基于GABAA受体亚型特异性作用的新药理学正在兴起。