Abstracts

Animal models of chronic epilepsy, such as the kainate-treated rat, may be useful in the discovery of new antiepileptic drugs (AEDs). The present study evaluated the effectiveness of carbamazepine on the frequency of spontaneous motor seizures in rats with kainate-induced epilepsy. Another aim of the study was to of develop a paradigm for continuous, long-term oral administration of potential AEDs., Single intraperitoneal (IP) injections of carbamazepine (10-100 mg/kg) were compared to vehicle [i.e., 20% (2-Hydroxypropyl)-[beta]-cyclodextrin] injections via six AED-versus-vehicle tests using a repeated-measures cross-over protocol. To establish an effective dose and the time-course of the anticonvulsant effect, two trials (8-9 rats per trial) evaluated single [italic]per os[/italic] [i.e., oral- by mouth (PO)] doses of 30 mg/kg and 100 mg/kg carbamazepine. Each PO trial included 3 AED-versus-vehicle tests comprised of carbamazepine-containing or control pellet feedings on alternate days with a recovery day between each treatment day. Based on the single-feeding studies, carbamazepine at 100 mg/kg was administered three times per day (TID) for 5 days., Carbamazepine significantly reduced seizure frequency at 10, 30, and 100 mg/kg after single IP injections, and caused complete seizure cessation during the 6-h post-drug epoch in 25% and 70% of animals at 30 and 100 mg/kg. Single IP injections and single oral feedings of 30 mg/kg and 100 mg/kg carbamazepine significantly (p[lt]0.0001) reduced seizure frequency relative to control treatments during 6-h and 22-h epochs following drug administration. A single feeding of carbamazepine (100 mg/kg PO) was significantly effective for 20 h and full recovery was complete within 23 h. Continuously administered carbamazepine (100 mg/kg PO, TID) significantly reduced seizure frequency by [gt]50% for 24 h and completely suppressed motor seizures in 50% of the animals tested., High doses of carbamazepine (30 and 100 mg/kg) were highly effective at suppressing spontaneous seizures, and were associated with a high percentage of motor seizure freedom. Administration of higher doses of carbamazepine did not further suppress spontaneous motor seizures. Oral administration of 30 mg/kg and 100 mg/kg carbamazepine was as effective as IP injections. Significant anticonvulsant effects of 100-mg/kg PO carbamazepine were sustained for the duration of the 5-day trial., (Supported by NIH (HLG) and (FED).)