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

Autor: Wu YV; The University of Toronto, Department of Pharmacology and Toxicology, Toronto, Canada. Electronic address: yinhao.wu@utoronto.ca., Burnham WM; The University of Toronto, Department of Pharmacology and Toxicology, Toronto, Canada.
Jazyk: angličtina
Zdroj: Epilepsy research [Epilepsy Res] 2018 Oct; Vol. 146, pp. 132-136. Date of Electronic Publication: 2018 Jul 29.
DOI: 10.1016/j.eplepsyres.2018.07.022
Abstrakt: 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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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