A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

Abstract

Purpose: Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs).The purpose of the present study was to evaluate the efficacy of cari-sbamate on spontaneous motor seizures in rats with kainate-induced epilepsy.Methods: Repeated, low-dose (5 mg/kg), intraperi- toneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h.Five 1-month trials (n = 8-10 rats) assessed the effects of 0.3, 1,3, 10, and 30 mg/kg carisbamate on spontaneous seizures.Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results: Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post- drug epoch in seven of the eight animals at 30 mg/kg.The effects of carisbamate (0.3-30 mg/kg) on spontaneous motor seizures appeared dose dependent.Conclusions: These data support the hypothesis that a repeated-measures, crossover protocol in animal models with spontaneous seizures is an effective method for testing AEDs.Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy.copyright © 2008 International League Against Epilepsy.