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

Epilepsia. 2008 Oct;49(10):1787-94. doi: 10.1111/j.1528-1167.2008.01657.x. Epub 2008 May 20.

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 carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy.

Methods: Repeated, low-dose (5 mg/kg), intraperitoneal 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 postdrug 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anticonvulsants / therapeutic use*
  • Carbamates / blood
  • Carbamates / therapeutic use*
  • Cross-Over Studies
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epilepsy / blood
  • Epilepsy / chemically induced*
  • Epilepsy / complications*
  • Fructose / analogs & derivatives
  • Fructose / therapeutic use
  • Kainic Acid*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / blood
  • Seizures / drug therapy*
  • Seizures / etiology
  • Time Factors
  • Topiramate
  • Video Recording

Substances

  • Anticonvulsants
  • Carbamates
  • S-2-O-carbamoyl-1-o-chlorophenyl-ethanol
  • Topiramate
  • Fructose
  • Kainic Acid