GABAPENTIN POTENTIATES THE ANTISEIZURE ACTIVITY OF CERTAIN ANTICONVULSANTS IN DBA 2 MICE/

Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagoni ze audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner. Gabapentin at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepi ne, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and val proate against sound-induced seizures in DBA/2 mice. The potentiation induced by gabapentin was greatest for diazepam, phenobarbital and val proate, less for felbamate and phenytoin and least for carbamazepine a nd lamotrigine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeu tic index of combined treatment of the above drugs + gabapentin was mo re favourable than that of the same drugs + saline. Since gabapentin d id not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interac tions, in terms of total or free plasma levels, are not probable. Howe ver, the possibility that gabapentin can modify the clearance from the brain of the anticonvulsant drugs studied can not be excluded. In add ition, gabapentin did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, gabapentin showed an ad ditive effect when administered in combination with certain classical anticonvulsants, most notably diazepam, phenobarbital, felbamate, phen ytoin and valproate. (C) 1998 Elsevier Science B.V. All rights reserve d.