设计和体外药理学的选择性gamma-aminobutyric acidC受体拮抗剂。

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Ragozzino D,伍德沃德RM,日本村田公司Y, Eusebi F,工头勒,Miledi R

设计和体外药理学的选择性gamma-aminobutyric acidC受体拮抗剂。

50摩尔杂志。1996年10月;(4):1024 - 30。

PubMed ID

8863850 (在PubMed

]

文摘

在哺乳动物中,受体的抑制性神经递质γ-氨基丁酸(GABA)分为三个药理类、GABAA表示,GABAB, GABAC。GABAC受体是由不敏感GABAA受体拮抗剂荷包牡丹碱和GABAB受体激动剂(-)巴氯芬。GABAC受体可能是蛋白质的异质群体。最广泛研究哺乳动物GABAC受体在外层视网膜的神经元。这些受体GABA-gated Cl - p子单元组成的通道,其中有两种亚型。GABAC受体的生理功能主要是未知的;确定功能,这将是有用的GABAC-selective配体。在先前的研究中,我们发现,isoguvacine GABAA-selective受体激动剂,和3-aminopropyl -(甲基)次膦酸(3-APMPA) GABAB-selective受体激动剂,显示视网膜GABAC受体亲和力。特别是3-APMPA拮抗剂与较低的微摩尔的效力(Kb大约1 microM)。在这里,我们报告的合成和药理特性(1、2、5、6-tetrahydropyridine-4-yl) methylphosphinic酸(TPMPA),混合isoguvacine和3-APMPA旨在保持亲和力GABAC但不与GABAA受体或GABAB受体。 Electrical assays show that TPMPA is a competitive antagonist of cloned human mu 1 GABAC receptors expressed in Xenopus laevis oocytes (Kb approximately 2 microM). TPMPA is > 100-fold weaker as an inhibitor of rat brain GABAA receptors expressed in oocytes (Kb approximately 320 microM) and has only weak agonist activity on GABAB receptors assayed in rat hippocampal slices (EC50 approximately 500 microM). TPMPA should be a useful pharmacological probe with which to investigate GABAC receptor function in the outer retina and in any other areas of the nervous system in which these types of receptor are present.

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药物

TPMPA