Abstract: Aim To examine the protective effects of allopreg nanolone against seizureon different animal models.Methods The protective Effects of allopreg nanolone against maximal electrical seizure(MES)and picrotoxin-induced seizurewerestudiedin C 57 mice 15 minutes after vehicle or drug intraperitoneal administration.Results In the MEStest, we found that pretreatment with the phenobarbital or allopregnanolone produced a dose-dependent protective Effect against seizure.The potency(ED₅₀ value)of phenobarbital in the MEStest was 2.40 mg· kg^-1, with 95 % confidence interval range from 1.22 to 4.72 mg· kg^-1.The potency(ED₅₀ value)of allopregnanolone in the MEStest was 0.086 mg·kg^-1, with 95 % confidence interval range from 0.037 to 0.201 mg· kg^-1, which was significantly higher than that of phenobarbital (P < 0.01).The combination study of half ED₅₀ values of phenobarbital and allopreg nanoloneresultedin a 80 % of protective effectin MEStest, which was higher than 50 % produced by either phenobarbital or allopreg nanolone at their ED₅₀ values respectively. This resultindicated that therewas a synerg ismbetween phenobarbital and allopregnanolone in theiranticonvulsant activities.In the picrotoxin test, we found that pretrea tment with the allopreg nanolone alsoproduced a dose-dependent protective effect against picrotoxin-induced seizure.The potencyof allopregnanolone in the picro toxin seizuretest was 0.123 mg· kg^-1, with 95 % confidence interval range from 0.058 to 0.263 mg· kg^-1.Conclusion Allopregnanolone(ip)could protect differentseizures in a dose-dependent manner, had a higher potencythan phenobarbital, and had synerg ismwith phenobarbital in the MEStest.

Key words: allopreg nanolone, phenobarbital, seizure, maximal electrical seizure, picrotoxin, ED₅₀