Fig. 8.

Neurosteroid SAR for seizure protection in the 6-Hz seizure test. (A) Percentage of animals responding to 6-Hz stimulation as a function of current intensity delivered through shock. All animals had 100% seizure activity at 32 mA. The dashed line perpendicular to the fitted data represents the current intensity at which 50% of animals experienced seizures. (C) Dose-response curves for neurosteroid modulation of 32 mA, 6-Hz–induced seizures in WT female mice. Neurosteroids were applied (s.c.) 15 minutes prior to stimulation. Seven structurally distinct pregnane-class neurosteroids were compared in seizure protection, using potency (ED₅₀, see Table 3) as the main index of anticonvulsant activity in vivo (3β-AP not shown because it did not provide full protection, even at the 100-mg/kg dose). n = 10 animals per group. AFX, alfaxolone (3α-hydroxy-5α-pregnan-11,20-dione).