The anti-seizure effects of IV 5α-dihydroprogesterone on amygdala-kindled seizures in rats

Objective: The present study investigated the anti-seizure effects of 5 alpha-dihydroprogesterone (DHP) in an animal model of human drug-resistant focal seizures with impaired awareness. DHP was administered via the intravenous (IV) route. Methods: Female Wistar rats were implanted with an electrode in the right basolateral amygdala. They were then kindled to 15 stage 5 seizures, stability tested, and cannulated in the jugular vein. Multiple doses of IV DHP were tested against focal electrographic seizures and secondarily generalized convulsions. The time-course of DHP's action was also examined. Results: The dose-response study, done at 5 min after injection, showed a dose-dependent suppression of both generalized and focal seizures, with an ED50 of 1.69 mg/kg for the generalized convulsive seizures and an ED50 of 3.48 mg/kg for the focal electrographic seizures. Ataxia, as rated by the Loscher ataxia scale, was also seen, with a TD50 of 3.57 mg/kg. The time-response study, done at the ED75 for focal seizure suppression, showed suppression of both generalized and focal seizures from immediately after injection to about 60 min post-injection. Significance: DHP has demonstrated anti-seizure effects in a drug-resistant model of human focal seizures with impaired awareness. Its analogs might be developed as new anti-seizure drugs.