Enhancement of GABA binding by benzodiazepines and related anxiolytics.
Enhancement of GABA binding by benzodiazepines and related anxiolytics.
复制标题
DOI：
10.1016/0014-2999(83)90494-6
复制
发表时间：
1983-05
影响因子：
5
通讯作者：
J. Skerritt;G. Johnston
中科院分区：
文献类型：
--
作者：
J. Skerritt;G. Johnston
几种苯二氮卓类药物（氯氮卓、氯硝西泮、地西泮、咪达唑仑、硝西泮和奥沙西泮）在50 mM Tris-柠檬酸盐缓冲液中以与体外取代[3 H]地西泮结合的浓度相当的浓度产生低亲和力GABA与新鲜洗涤的脑细胞膜结合的浓度依赖性增强。非苯二氮卓类抗焦虑药CL 218872和佐匹克隆也增强了GABA结合，而中枢非活性苯二氮卓类Ro 5 -4864未能改变GABA结合。苯二氮卓类拮抗剂Ro 15 -1788不改变GABA结合，但可有效拮抗100 nM地西泮对GABA结合的刺激。这些药理学特征表明，GABA与低亲和力受体位点结合的增强可能引起苯二氮卓类药物的许多体内作用。
Several benzodiazepines (chlordiazepoxide, clonazepam, diazepam, midazolam, nitrazepam and oxazepam) produced a concentration-dependent enhancement of low affinity GABA binding to fresh, washed brain membranes in 50 mM Tris-citrate buffer at concentrations comparable to those displacing [3H]diazepam binding in vitro. The nonbenzodiazepine anxiolytics CL218872 and zopiclone also enhanced GABA binding, while the centrally inactive benzodiazepine Ro5-4864 failed to alter GABA binding. The benzodiazepine antagonist, Ro15-1788 did not alter GABA binding but potently antagonised stimulation of GABA binding by 100 nM diazepam. These pharmacological characteristics suggest than an enhancement of the binding of GABA to low affinity receptor sites may give rise to many of the in vivo actions of the benzodiazepines.