中枢神经系统抑制剂加速35S - TBPS结合的解离，而γ-氨基丁酸（GABA）增强它们的置换效力。

CNS depressants accelerate the dissociation of 35S-TBPS binding and GABA enhances their displacing potencies.

作者信息

Maksay G, Ticku M K

机构信息

Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.

出版信息

Life Sci. 1988;43(16):1331-7. doi: 10.1016/0024-3205(88)90589-9.

DOI:10.1016/0024-3205(88)90589-9

PMID:2845220

Abstract

The specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex. The displacing potencies of eleven CNS depressants and three convulsants were determined in the presence of 1 microM GABA and 10 nM R 5135. GABA enhanced the displacing potencies of depressants of most diverse chemical structures: diaryltriazine (LY 81067), pyrazolopyridine (etazolate), cinnamide, glutarimide, 2,3-benzodiazepine (tofizopam) and alcohol derivatives, barbiturates, (+)etomidate, methaqualone and meprobamate. In contrast, the IC50 values of convulsants (picrotoxinin, pentetrazol and the barbiturate enantiomer S(+) MPPB) were not significantly affected. The depressants accelerated either basal or GABA-augmented dissociation of 35-TBPS mainly by increasing the contribution of its rapid first phase.

摘要

研究了35S-叔丁基双环硫代磷酸酯（TBPS）在大鼠大脑皮质突触体膜中的特异性结合。在1微摩尔/升γ-氨基丁酸（GABA）和10纳摩尔/升R 5135存在的情况下，测定了11种中枢神经系统抑制剂和3种惊厥剂的置换效力。GABA增强了多种化学结构抑制剂的置换效力：二芳基三嗪（LY 81067）、吡唑并吡啶（乙唑酯）、肉桂酰胺、戊二酰亚胺、2,3-苯并二氮杂卓（托非唑泮）和醇衍生物、巴比妥酸盐、（+）依托咪酯、甲喹酮和甲丙氨酯。相比之下，惊厥剂（印防己毒素、戊四氮和巴比妥酸盐对映体S（+）MPPB）的半数抑制浓度（IC50）值未受到显著影响。这些抑制剂主要通过增加其快速第一相的贡献，加速了35-TBPS的基础解离或GABA增强的解离。