11β-Hydroxylase Inhibitors Protect Against Seizures in Mice by Increasing Endogenous Neurosteroid Synthesis

The study demonstrated that the 11β-hydroxylase inhibitors metyrapone and etomidate provided protection against seizures in mice by increasing the synthesis of neurosteroids, particularly allotetrahydrodeoxycorticosterone (THDOC), which modulates GABAA receptors. Metyrapone showed dose-dependent seizure protection, with a more potent effect observed 6 hours after administration. Etomidate also exhibited protective effects at both 30 minutes and 6 hours post-administration. The neurosteroid synthesis inhibitor finasteride reduced the anticonvulsant effects of these inhibitors at 6 hours, indicating that the delayed seizure protection was due to the slow build-up of neurosteroids. Early seizure protection was found to be independent of neurosteroids.