The anti-seizure effects of IV 5α-dihydroprogesterone on amygdala-kindled seizures in rats
- PMID: 30149307
- DOI: 10.1016/j.eplepsyres.2018.07.022
The anti-seizure effects of IV 5α-dihydroprogesterone on amygdala-kindled seizures in rats
Abstract
Objective: The 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.
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 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.
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.
Keywords: 5a-dihydroprogesterone; 5a-pregnane-3,20-dione; Complex partial seizures; Dose-response study; Intravenous injection; Time-response study.
Copyright © 2018 Elsevier B.V. All rights reserved.
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