Neurosteroids as Endogenous Modulators of Epileptic Seizures

Neurosteroids are a family of steroidal compounds which produce a variety of biological effects, mainly by interacting with the γ-aminobutyric acid receptor A (GABAA). Among neurosteroids, allopregnanolone and tetrahydrodeoxycorticosterone are positive modulators of GABAA receptors that were shown to counteract seizures in animal models. However, it is still to be defined the role of neurosteroids both in patients affected by epilepsy and in animal models based on spontaneously recurrent seizures. By using finasteride, an irreversible inhibitor of the enzyme 5α-reductase, we found that allopregnanolone cerebral levels were significantly decreased in rats treated with the convulsant pilocarpine. Interestingly, this decrease was followed by enhanced epileptogenesis. We also described a case of antiepileptic drug resistance in a patient that was maintained on finasteride to treat a dermatological disorder: seizures ceased by withdrawing finasteride. These findings point to a modulatory role of allopregnanalone and other neurosteroids on epileptic seizures.