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Role of beta(2/3)-specific GABA-A receptor isoforms in the development of hippocampus kindling epileptogenesis

机译:Beta(2/3)的作用 - 特异性GABA-A受体同种型在海马的发展中的开发中的癫痫发生

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摘要

Objective: Subunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for beta(2/3)-subunit containing GABA-A receptors (beta(2/3)-selective PAMs) that are nonbenzodiazepine site-mediated and do not show an a-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance. In this study, we used three novel beta(2/3)-selective PAMs (2-261, 2-262, and 10029) with differential beta(2/3)-subunit potency to identify the role of beta(2/3)-selective receptor isoforms in limbic epileptogenesis.
机译:目的:亚基特异性阳性颠氨酸 - a(GABA-A)受体常用于揭示GABA-A受体同种型在脑功能中的作用。 最近,我们为含有GABA-A受体(Beta(2/3) - 选择性PAM)的β(2/3)-subit,设计了一种用于β(2/3)的-subit的新型PAMS选择性,所述β-苯并二氮杂己胺位点介导,并没有显示A-亚基同种型选择性, 然而,具有降低的镇静,认知障碍和耐受性的抗焦力效果。 在这项研究中,我们使用了三种新的β(2/3) - 选择性PAM(2-261,2-262和10029),差异β(2/3)-subinit效力以鉴定β的作用(2/3 ) - 肢体癫痫发生剂中的选择性受体同种型。

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