Protective effects of allopregnanolone against different seizure models in mice / 中国临床药理学与治疗学

ABSTRACT

Aim To examine the protective effects of allopregnanolone against seizure on different animal models.Methods　The protective effects of allopregnanolone against maximal electrical seizure (MES) and picrotoxin-induced seizure were studied in C57 mice 15 minutes after vehicle or drug intraperitoneal administration.Results　In the MES test, 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 MES test 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 MES test 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 allopregnanolone resulted in a 80% of protective effect in MES test, which was higher than 50% produced by either phenobarbital or allopregnanolone at their ED50 values respectively. This result indicated that there was a synergism between phenobarbital and allopregnanolone in their anticonvulsant activities. In the picrotoxin test, we found that pretreatment with the allopregnanolone also produced a dose-dependent protective effect against picrotoxin-induced seizure. The potency of allopregnanolone in the picrotoxin seizure test 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 different seizures in a dose-dependent manner,had a higher potency than phenobarbital,and had synergism with phenobarbital in the MES test.