Effect of ganaxolone on flurothyl seizures in developing rats

Purpose: To determine the effects of a newly synthesized epalon, ganaxolone (GNX), on primarily generalized seizures in rats of various ages during development. Epalons are classified as neuroactive steroids that interact at unique site of the GABA(A) receptor-Cl(-) channel complex in the central nervous system. Methods: Sprague-Dawley male rats were used at 9, 15, 30, and 60 postnatal days (PN), GNX dissolved in 2-hydroxypropyl-β- cyclodextrine was administered intraperitoneally in different doses at various time points before flurothyl testing. The incidence and threshold of clonic and tonic-clonic flurothyl seizures were evaluated. Behavioral changes were also assessed. Results: In all age groups, the effects of GNX were dose dependent and more prominent 10 min after its administration. In PN 60 and PN 30 rats, GNX had dose-dependent anticonvulsant effects; tonic-clonic seizures were more sensitive to GNX treatment than clonic seizures. In PN 15 and PN 9 rats, GNX demonstrated dose- and time-dependent anticonvulsant effects against both types of flurothyl-induced seizures. GNX was more effective in PN 15 rats than in other age groups, but at doses that altered motor behavior. Conclusions: GNX has anticonvulsant effects against flurothyl- induced seizures in all age groups tested. Its effects are more prominent in the two younger age groups, especially in PN 15 rats, but are associated with motor side effects.