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目的 在大鼠杏仁核点燃模型研究MK 80 1(地佐西平 )及其联合用药的抗癫痫作用。方法 建立大鼠杏仁核慢性电刺激点燃模型 ,测定不同剂量的MK 80 1对点燃模型各项指标的影响 ,探讨MK 80 1与其他抗癫痫药的协同作用 ,用氨基脲诱发的小鼠惊厥模型测定MK 80 1抗惊厥作用。结果 MK 80 1(0 1～ 0 2 5mg·kg- 1)可剂量依赖性抑制杏仁核点燃 ,缩短后放电时程 ,降低Racine’s分级 ;在对点燃均无明显影响的剂量下 ,MK 80 1(0 0 5mg·kg- 1)与抗癫痫药 (苯巴比妥、丙戊酸及尼卡地平 )合用可缩短后放电时程或降低Racine’s分级。MK 80 1(0 1～ 0 2 5mg·kg- 1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率。结论 MK 80 1具有抑制大鼠杏仁核点燃的作用 ,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性 ,为临床的合并用药提供实验依据
OBJECTIVE: To study the anti-epileptic effect of MK 80 1 (dexrazepam) and its combination therapy in rat amygdaloid lighting model. Methods A rat model of amygdala induced by chronic electrical stimulation was established. The effects of different doses of MK 80 1 on various indexes of the model were tested. The synergistic effect of MK 80 1 and other antiepileptic drugs was investigated. The model of seizures induced by semicarbazide The anticonvulsant effect of MK 80 1 was determined. Results MK 80 1 (0 1 ~ 0 2 5 mg · kg -1) could inhibit the amygdalaeignition in a dose-dependent manner, shorten the post discharge time and decrease the Racine’s grade. In the dose of MK 80 1 ( 0 0 5mg · kg-1) combined with anti-epileptic drugs (phenobarbital, valproic acid and nicardipine) can shorten the post-discharge duration or reduce Racine’s grade. MK 80 1 (0 1 ~ 0 2 5 mg · kg -1) significantly reduced the latency, seizure and mortality in mice induced by semicarbazide. Conclusion MK 80 1 can inhibit the amygdala in rats and enhance the antiepileptic activity of phenobarbital, valproic acid and nicardipine, and provide experimental basis for clinical combination therapy