ANTICONVULSANT ACTIVITY OF FELBAMATE IN AMYGDALA KINDLING MODEL OF TEMPORAL-LOBE EPILEPSY IN RATS

Purpose: Previous studies have demonstrated that felbamate (FBM, 2-phe nyl-1,3-propanediol dicarbamate) at nontoxic doses exerts potent antic onvulsant activity in a variety of animal epilepsy or seizure models. We further characterized the anticonvulsant activity of FBM by using t he kindling model of temporal lobe epilepsy (TLE). Methods: The experi ments were performed in fully kindled rats. The anticonvulsant effect of FBM was assessed by determining seizure severity, afterdischarge (A D) duration and seizure duration either at the focal seizure threshold , or after suprathreshold stimulation. In addition, the neurological p erformance of kindled rats after FBM administration was evaluated in t he open field and by the rotorod test. Results: FBM at doses of 12.5-5 0 mg/kg, given intraperitoneally (i.p.) 60 min before testing, dose-de pendently increased the AD threshold (ADT). The maximal effect was ach ieved after the highest dose tested and reached almost 600% of the con trol ADT. This dose of FBM significantly diminished other seizure para meters, e.g., seizure severity, seizure duration, and AD duration. Whe n the rats were stimulated with suprathreshold current (500 mu A) seiz ure severity was moderately but significantly reduced. No behavioral a bnormalities were noted in kindled rats after administration of either of the doses. Conclusions: FBM potently increases the threshold for f ocal seizures and reduces seizure severity, seizure duration, and AD d uration at doses that produce no adverse behavioral effects in amygdal a-kindled rats. These data are thus compatible with clinical experienc e with FBM in TLE and substantiate that kindling is a good predictor o f anticonvulsant activity against TLE.