Anticonvulsant activity of felbamate in amygdala kindling model of temporal lobe epilepsy in rats.
OBJECTIVE
Previous studies have demonstrated that felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate) at nontoxic doses exerts potent anticonvulsant activity in a variety of animal epilepsy or seizure models. We further characterized the anticonvulsant activity of FBM by using the kindling model of temporal lobe epilepsy (TLE).


METHODS
The experiments were performed in fully kindled rats. The anticonvulsant effect of FBM was assessed by determining seizure severity, afterdischarge (AD) duration and seizure duration either at the focal seizure threshold, or after suprathreshold stimulation. In addition, the neurological performance of kindled rats after FBM administration was evaluated in the open field and by the rotorod test.


RESULTS
FBM at doses of 12.5-50 mg/kg, given intraperitoneally (i.p.) 60 min before testing, dose-dependently increased the AD threshold (ADT). The maximal effect was achieved after the highest dose tested and reached almost 600% of the control ADT. This dose of FBM significantly diminished other seizure parameters, e.g., seizure severity, seizure duration, and AD duration. When the rats were stimulated with suprathreshold current (500 microA) seizure severity was moderately but significantly reduced. No behavioral abnormalities were noted in kindled rats after administration of either of the doses.


CONCLUSIONS
FBM potently increases the threshold for focal seizures and reduces seizure severity, seizure duration, and AD duration at doses that produce no adverse behavioral effects in amygdala-kindled rats. These data are thus compatible with clinical experience with FBM in TLE and substantiate that kindling is a good predictor of anticonvulsant activity against TLE.
Wlaź
P
P
Faculty of Veterinary Medicine, Agricultural University, Lublin, Poland.
Löscher
W
W
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004569:Electroencephalography / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D000078328:Felbamate; D005260:Female; D006801:Humans; D007696:Kindling, Neurologic / Q000502:physiology*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate