左乙拉西坦与苯妥英钠协同抗小鼠最大电惊厥作用实验研究

目的探讨左乙拉西坦(Levetiracetam)与苯妥英钠(Phenytoin Sodium)协同抗小鼠最大电惊厥的作用.方法昆明种小鼠200只,雌雄各半,随机分为正常对照组、左乙拉西坦高中低剂量组、苯妥英钠高中低剂量组,测定抗最大电惊厥作用的量效关系,并根据两药的量效关系确定左乙拉西坦与苯妥英钠协同作用的高中低剂量组,每组20只小鼠,正常对照组给予等容积的生理盐水,其余给予相应的药物,灌胃剂量10 m L/kg.灌胃给药后50 min,给予小鼠电刺激,以小鼠下肢和全身出现强直性抽搐作为强直性惊厥指标,记录惊厥数,计算惊厥率.结果左乙拉西坦和苯妥英钠两药均有良好的抗最大电惊厥作用的量效关系,选择阈下剂量的左乙拉西坦和苯妥英钠合用后,高剂量组的惊厥发生率为10%,中剂量组惊厥发生率为40%,能产生明显的协同增效作用.结论阈下剂量的左乙拉西坦和苯妥英钠合用具有明显的协同抗小鼠最大电惊厥作用,并有良好的量效关系.

Experimental Research on the Effects of Levetiracetam Combined with Phenytoin Sodium on Anti-maximal Electric Seizure in Mice

Objective To investigate the synergistic effect of levetiracetam combined with phenytoin sodium on anti-maximal electric seizure ( MES ) in mice. Methods A total of 100 male and 100 female mouse were randomly divided into the normal control group,high dose levetiracetam group,middle dose levetiracetam group, low dose levetiracetam group,high dose phenytoin sodium group,middle dose phenytoin sodium group and low dose phenytoin sodium group. Dose-effect relationships of anti-MES were measured. According to the dose-effect relationships,the corresponding anti-MES’ s effect drug doses were determined. They were high dose group, middle dose group and low dose group with 20 mouse in each group. The control group was given 10 mL/kg saline by gavage,and the other three groups were administrated the corresponding drugs. After 50 minutes,all the mice were treated with electricity. When the lower limbs and the whole body of the mice showed tonic convulsions,the convulsion frequencies were recorded and then the convulsion rates were calculated. Results Both levetiracetam and phenytoin sodium had good anti-electric convulsion effect and showed obvious dose-effect relationship. The combination use of subthreshold doses of levetiracetam and phenytoin sodium could produce synergistic anti-maximal convusion effect,with convulsion rate of 10% in high dose group and the rate of 40% in middle dose group. Conclusion The subthreshold dose of levetiracetam and phenytoin has obvious synergistic anti-MES effect and shows a good dose-effect relationship.