Abstract
ObjectiveThe present study investigated the anti-seizure effects of 5α-dihydroprogesterone (DHP) in an animal model of human drug-resistant focal seizures with impaired awareness. DHP was administered via the intravenous (IV) route. MethodsFemale 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. ResultsThe 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 Löscher 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. SignificanceDHP 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.
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