四氢孕酮与苯巴比妥对保护小鼠最大电休克惊厥的协同作用(英文)

目的:观察四氢孕酮与苯巴比妥的抗惊厥相互作用。方法:采用小鼠最大电休克惊厥(MES)试验,测定四氢孕酮和/或苯巴比妥的保护作用;并采用小鼠大脑皮质膜制备,用氚标氟硝安定检测四氢孕酮和/或苯巴比妥对GABA_A受体复合物的调节。结果:苯巴比妥(0.5-50mg·kg~(-1))对小鼠最大电休克惊厥具剂量依赖性的保护作用,其ED_(50)为2.61mg·kg~(-1),95％可信限为1.59-4.26mg·kg~(-1)。同样,四氢孕酮(0.01-1.0mg·kg~(-1))也有剂量依赖性的保护作用,其ED_(50)为0.11(0.06-0.18)mg·kg~(-1)。四氢孕酮和苯巴比妥联合用药(1:20)的ED_(50)为0.73(0.44-1.21)mg·kg~(-1),Q值小于1。测定四氢孕酮和/或苯巴比妥增加氚标氟硝安定的结合,其浓度效应曲线与功能性协同作用的理论曲线相符。结论:四氢孕酮和苯巴比妥对抗小鼠最大电休克惊厥有协同作用;两者对增加氚标氟硝安定与GABA_A受体复合物的结合也有功能性协同作用。

Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice

AIM: To examine the interactions of allopregnanolone and phenobarbital for the protection against seizures. METHODS: The protective activity of allopregnanolone and/or phenobarbital against seizures was studied in the C57 mice, using the maximal electroshock seizure (MES) test. The modulations by allopregnanolone and/or phenobarbital at the GABA(A) receptor were also characterized using the [3H]flunitrazepam binding in the membrane preparation of mouse cerebral cortex. RESULTS: Pretreatment with phenobarbital produced a dose-dependent protective effect against seizures. The ED50 value of phenobarbital was 2.61 (95 % confidence limits: 1.59 - 4.26) mg . kg-1. Likewise, the ED50 value of allopregnanolone was 0.11 (0.06 - 0.18) mg . kg-1. The combination of allopregnanolone and phenobarbital (1:20) resulted in an ED50 value of 0.73 (0.44 - 1.21) mg . kg-1 with the Q value smaller than 1. In measuring the enhancement of [3H]flunitrazepam binding, we found that the pattern for the concentration-effect curves of phenobarbital with or without allopregnanolone was consistent with that of the theoretical curves of functional synergism. CONCLUSION: There was a synergism between allopregnanolone and phenobarbital for the protective activity against seizures. Also there was a functional synergism between these two agents for the enhancement of [3H]flunitrazepam binding to the GABAA receptor complex in the brain.