Anticonvulsant and antiepileptogenic effects of fluorofelbamate in experimental status epilepticus

Abstract

Purpose: To examine the seizure-protective properties of fluorofelbamate, a felbamate analog, on acute and chronic seizures in an experimental model of self-sustaining status epilepticus (SSSE). Methods: SSSE was induced by stimulation of the perforant path for 30 min (PPS) through chronically implanted electrodes in free-running adult male Wistar rats. Fluorofelbamate was injected intravenously (i.v.) either 10 min, or 40 min after SSSE induction. Seizure and spike profiles were analyzed off-line. Results: Fluorofelbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose-dependent manner. While a dose of 50 mg kg −1was ineffective, 100 and 200 mg kg −1reduced cumulative seizure time from 393 ± 10 min to 15 ± 8 min and 2.4 ± 0.5 min respectively. Administration of fluorofelbamate (200 and 300 mg kg −1) at a late stage of SSSE, which is refractory to treatment with conventional anticonvulsants, also significantly attenuated seizures. Acute fluorofelbamate treatment (200 mg kg −110 min after PPS) significantly decreased the frequency of spontaneous seizures which follow SSSE after a ‘latent’ interval. Moreover, in contrast to control animals, fluorofelbamate-treated rats showed regression of spontaneous seizures, and an apparent remission of epilepsy within 2 months after SSSE. Conclusions:Acute treatment of SSSE with fluorofelbamate showed strong anticonvulsant effects even during the late stages of SSSE. In this model, it also displayed antiepileptogenic properties: it reduced the severity of chronic epilepsy after SSSE and lead to apparent remissions of that epilepsy.