Morimoto K, Sanei T, Sato K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Epilepsia. 1993 Nov-Dec;34(6):1123-9. doi: 10.1111/j.1528-1157.1993.tb02144.x.
We made a comparative study of the anticonvulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [gamma-aminobutyric acid (GABA) receptor agonist 25-100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose-dependent manner. SKF89976A (GABA uptake inhibitor 0.5-2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, gamma-vinyl GABA (GABA catabolic enzyme inhibitor, GVG 50-200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.
我们对γ-氨基丁酸（GABA）激动剂对猫杏仁核或海马点燃性癫痫发作的抗惊厥作用进行了比较研究。普罗加比（PGB）[γ-氨基丁酸（GABA）受体激动剂，腹腔注射25 - 100毫克/千克]以剂量依赖方式显著降低了点燃性癫痫发作阶段和发作后放电（AD）持续时间。SKF89976A（GABA摄取抑制剂，腹腔注射0.5 - 2.0毫克/千克）也显著降低了点燃性癫痫发作阶段。SKF89976A的毒性剂量导致全身性阵发性脑电图放电和肌阵挛，但点燃灶中的AD产生被完全抑制。此外，γ-乙烯基氨基丁酸（GABA分解酶抑制剂，GVG，腹腔注射50 - 200毫克/千克）显著降低了癫痫发作阶段，同时导致AD持续时间延长。相比之下，巴氯芬（选择性GABAB受体激动剂，1或5毫克/千克）对点燃性癫痫发作的任何参数均未显示出抗惊厥作用。因此，这些增强GABAA系统抑制功能的GABA激动剂对部分性发作和继发性全身性边缘性癫痫发作具有强大的抗惊厥作用。
