ANTICONVULSANT EFFECT OF FELBAMATE IN THE PENTYLENETETRAZOLE KINDLINGMODEL OF EPILEPSY IN THE RAT

The present study was designed to examine the ability of felbamate, a novel antiepileptic agent, to antagonize the increase in seizure sever ity (i.e., chemical kindling) produced by chronic treatment with initi ally subconvulsant doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, ii?, three times a week) for 8 consecutive weeks. Two other groups of rats received felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment with felbamate at either dose prevented the progression of rank of seizures during chronic tre atment with PTZ. Thus, the mean seizure score by the end of the chroni c treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate ( 300 mg/kg, i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.). Felbamate also antagonized the long-term increase i n the sensitivity to the convulsant effects of GABA function inhibitor s observed in PTZ-kindled rats. Thus, the administration of a challeng e dose of isoniazid (120 mg/kg, s.c.), picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after the end of the chron ic treatment regimen, induced convulsions in > 80% of PTZ-kindled rats and in < 20% of rats treated with PTZ + felbamate(400 mg/kg). The res ults are discussed in terms of the multiple mechanisms that can contri bute to the anticonvulsant action of felbamate in the PTZ kindling mod el of epilepsy.