Finasteride, a 5α-Reductase Inhibitor, Blocks the Anticonvulsant Activity of Progesterone in Mice

摘要: Progesterone is an effective anticonvulsant against pentylenetetrazol (PTZ) seizures. This action hypothesized to require the metabolic conversion of progesterone γ-aminobutyric acidA receptor potentiating neuroactive steroid allopregnanolone by 5α-reductase isoenzymes followed 3α-hydroxy oxidoreduction. We evaluated this possibility using competitive inhibitor finasteride. (50–200 mg/kg, i.p.) protected mice PTZ-induced seizures in a dose-dependent manner (ED50, 94 mg/kg). Pretreatment with finasteride (50–300 produced 146 mg/kg) reversal protective effects (2 × ED50 dose = 188 In contrast, (up 300 failed affect activity (10–30 i.p.; ED50, 12 Finasteride did not block effect high doses (250–350 on tonic hindlimb extension maximal electroshock seizure test (progesterone 235 The can be blocked inhibition, providing strong evidence that model mediated its active metabolite allopregnanolone.