The Anticonvulsant Effects of 5a-dihydroprogesterone in the Rat Amygdala-Kindled Model

The present study investigated the anti-seizure effects of 5-dihydroprogesterone (5-DHP) in an animal model of human drug-resistant complex partial seizures - the rat amygdala-kindling model - using different routes of administration and solvents. 5-DHP in -cyclodextrin administered via the subcutaneous (SQ) route was weakly effective (Rmax=30%). 5-DHP via the intraperitoneal (IP) route in the "benzyl" vehicle, however, suppressed both generalized and focal seizures with ataxia shortly after injection; and generalized seizures around 130 minutes post-injection. The "benzyl" vehicle itself, however, was active at the earlier time, and benzyl alcohol was found to be anticonvulsant. 5-DHP in -cyclodextrin via the intravenous (IV) route suppressed both generalized seizures and focal seizures, with ataxia. A time-response IV study at 5mg/kg showed immediate onset of anticonvulsant action that lasted for about 60 minutes post-injection. In conclusion, 5-DHP demonstrated efficacy in the present study, and 5-DHP analogs might be developed as a new anti-seizure therapy.M.Sc.2019-11-06 00:00:0