γ-氨基丁酸（GABA）对两种新型非苯二氮䓬类药物PK 8165和CGS 8216与大鼠脑内苯二氮䓬受体体外结合的影响。

The effect of GABA on in vitro binding of two novel non-benzodiazepines, PK 8165 and CGS 8216, to benzodiazepine receptors in the rat brain.

作者信息

Morelli M, Gee K W, Yamamura H I

出版信息

Life Sci. 1982 Jul 5;31(1):77-81. doi: 10.1016/0024-3205(82)90403-9.

Abstract

The effect of gamma-aminobutyric acid (GABA) on the binding of PK 8165, a quinoline derivative, and CGS 8216, a pyrazoloquinoline, was assessed in two different regions of the rat brain. PK 8165, a compound with reported anxiolytic properties, inhibited [3H]-propyl beta-carboline-3-carboxylate labeled receptors in the cerebellum with an IC50 of 844 nM and 370 nM in the absence and presence of micro M GABA, respectively. GABA (100 micro M) was less effective in the cerebral cortex, decreasing the IC50 value from 280 to 197 nM. In saturation isotherm studies with [3H]-CGS 8216, a benzodiazepine receptor antagonist, GABA (100 micro M) induced a small but significant reduction in the apparent affinity of [3H]-CGS 8216 for benzodiazepine receptors in the cerebral cortex but the Bmax was unchanged.

摘要

在大鼠脑的两个不同区域评估了γ-氨基丁酸（GABA）对喹啉衍生物PK 8165和吡唑并喹啉CGS 8216结合的影响。PK 8165是一种具有抗焦虑特性的化合物，在不存在和存在微摩尔GABA的情况下，分别以844 nM和370 nM的IC50抑制小脑[3H]-丙基β-咔啉-3-羧酸酯标记的受体。GABA（100微摩尔）在大脑皮层中的作用较小，将IC50值从280 nM降至197 nM。在用苯二氮䓬受体拮抗剂[3H]-CGS 8216进行的饱和等温线研究中，GABA（100微摩尔）使[3H]-CGS 8216对大脑皮层中苯二氮䓬受体的表观亲和力有小幅但显著的降低，但最大结合容量（Bmax）不变。