Role of Neurosteroids in the Anticonvulsant Activity of Midazolam

The study demonstrated that midazolam's anticonvulsant activity in a PTZ seizure model in mice was partly mediated by neurosteroids. Midazolam increased the seizure threshold in a dose-dependent manner, and this effect was reduced by finasteride, a neurosteroid synthesis inhibitor, indicating the involvement of neurosteroids. Conversely, metyrapone, which enhances neurosteroid synthesis, further increased the seizure threshold when used with midazolam. The role of the translocator protein (TSPO) in this process was supported by the inhibition of midazolam's effects by PK 11195, a TSPO ligand. The study concluded that midazolam's anticonvulsant effects were linked to neurosteroid synthesis, potentially through TSPO interaction, highlighting the significant role of neurosteroids in modulating GABAA receptors.