Rastogi S K, Ticku M K
Pharmacol Biochem Behav. 1985 Aug;23(2):285-8. doi: 10.1016/0091-3057(85)90571-4.
The purpose of the present investigation was to determine the possible role of GABAergic mechanism in the convulsant action of RO5-4864. Benzodiazepines (BZ) and other agents which facilitate central GABAergic transmission delayed the onset of facial and forelimb clonus, whereas tonic hind limb extension was blocked in a dose-dependent manner. RO5-4864-induced convulsions were blocked by diazepam, clonazepam, pentobarbital, ethanol and amino-oxyacetic acid (AOAA). RO5-4864-induced convulsions were not blocked by the BZ antagonist RO15-1788. Specifically, RO15-1788 caused a decrease in the onset of severity component of tonic seizures, which tended to become generalized and precipitated in a tonic extension of the hindlimbs. Further, subconvulsive doses of a direct GABA receptor antagonist, bicuculline, enhanced the proconvulsant action of RO5-4864, indicating thereby a potential antagonism of the central GABAergic transmission. These observations strongly suggest that RO5-4864 probably elicits convulsions by selective impairment of the GABAergic transmission.
本研究的目的是确定γ-氨基丁酸（GABA）能机制在RO5-4864惊厥作用中可能发挥的作用。苯二氮䓬类药物（BZ）和其他促进中枢GABA能传递的药物可延迟面部和前肢阵挛的发作，而强直性后肢伸展则以剂量依赖的方式被阻断。地西泮、氯硝西泮、戊巴比妥、乙醇和氨氧乙酸（AOAA）可阻断RO5-4864诱发的惊厥。RO5-4864诱发的惊厥未被BZ拮抗剂RO15-1788阻断。具体而言，RO15-1788使强直性发作严重程度成分的发作时间缩短，强直性发作倾向于泛化并在后肢强直性伸展中加剧。此外，亚惊厥剂量的直接GABA受体拮抗剂荷包牡丹碱可增强RO5-4864的惊厥前作用，从而表明对中枢GABA能传递存在潜在拮抗作用。这些观察结果强烈表明，RO5-4864可能通过选择性损害GABA能传递而引发惊厥。
