慢性苯二氮䓬类配体暴露后激动剂效力与GABA敏感性变化及抗惊厥耐受性的关系。

Relationship of agonist efficacy to changes in GABA sensitivity and anticonvulsant tolerance following chronic benzodiazepine ligand exposure.

作者信息

Hernandez T D, Heninger C, Wilson M A, Gallager D W

机构信息

Yale University School of Medicine, Department of Psychiatry, Abraham Ribicoff Research Facilities and Connecticut Mental Health Center, New Haven, CT.

出版信息

Eur J Pharmacol. 1989 Nov 7;170(3):145-55. doi: 10.1016/0014-2999(89)90535-9.

DOI:10.1016/0014-2999(89)90535-9

PMID:2515976

Abstract

Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16-6028 and the antagonist, Ro 15-1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16-6028 and no changes were observed following chronic Ro 15-1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.

摘要

将不同效能的苯二氮䓬配体，包括激动剂地西泮、部分激动剂Ro 16 - 6028和拮抗剂Ro 15 - 1788，连续3周对大鼠进行体内给药。GABA敏感性各种测量指标的变化幅度可直接与激动剂效能增加相关：地西泮长期治疗后出现最大变化，部分激动剂Ro 16 - 6028治疗后出现中等变化，而Ro 15 - 1788长期给药后未观察到变化。变化幅度也可与长期暴露于这些苯二氮䓬配体后对抗惊厥效能耐受性发展的可能性增加相关。