ganaxolone and Epilepsy--Temporal-Lobe

Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABAA receptors, may represent a new treatment approach for epilepsy. Here we demonstrate that pretreatment with ganaxolone (1.25-20 mg/kg, s.c.) causes a dose-dependent suppression of behavioral and electrographic seizures in fully amygdala-kindled female mice, with nearly complete seizure protection at the highest dose tested. The ED50 for suppression of behavioral seizures was 6.6 mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1 mg/kg, s.c.). To the extent that amygdala kindling represents a model of mesial temporal lobe epilepsy, this study supports the utility of ganaxolone in the treatment of patients with temporal lobe seizures.

Topics: Amygdala; Animals; Anticonvulsants; Clonazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Female; Kindling, Neurologic; Mice; Mice, Inbred C57BL; Pregnanolone; Seizures