MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响(英文)

Effect of combination of dizocilpine with general antiepileptic drugs on amygdala kindling models in rats

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 。

Aim To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kin dling models in rats and the effects of its combination with general antiepilept ic drugs. Methods To establish amygdala kindling models in rats and observe the effect of dizocilp ine on kindling models and its combination with general antiepileptic drugs (phe nobarbital, valproate and nicardipine) at ineffective dose. The influence of diz ocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observe d. Results Dizocilpine (0 1-0 25 mg·kg -1 , ip) was shown to dose-dependently i nhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P<0 01). The combination of dizocilpine with phe nobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P<0 01). Dizocilpine (0 1-0 25 mg·kg -1 , ip) s ignificantly prolonged the latency and reduced the rate of convulsions and death in mice. Conclusion Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiep ileptic activity of phenobarbital, valproate and nicardipine, indicating that th ese combination may provide a new approach for treating epilepsy.