THE INFLUENCE OF L-N-G-NITROARGININE METHYL-ESTER, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, UPON THE ANTICONVULSIVE ACTIVITY OF CONVENTIONAL ANTIEPILEPTIC DRUGS AGAINST MAXIMAL ELECTROSHOCK IN MICE

N-G-Nitro-L-arginine methyl ester (L-NAME, an unspecific nitric oxide synthase inhibitor), applied at 1 and 40 mg/kg, did not influence the electroconvulsive threshold, but impaired the anticonvulsant activity of valproate (at 40 mg/kg) and phenobarbital (at 1 and 40 mg/kg). No e ffect was observed in the case of carbamazepine and diphenylhydantoin. The effect of L-NAME upon the protective activity of phenobarbital wa s not reversed by L-arginine (500 mg/kg), a source of endogenous nitri c oxide. Moreover, this nitric oxide synthase inhibitor did not alter the plasma levels of antiepileptic drugs studied, so a pharmacokinetic interaction is not probable. L-NAME per se (40 mg/kg) caused a modera te motor impairment but did not affect longterm memory. The combined t reatment of L-NAME and antiepileptic drugs (providing a 50% protection against maximal electroshock) resulted in motor disturbances. On the other hand, mice performed the memory task better upon combined treatm ent of antiepileptic drugs with L-NAME compared to antiepileptic drugs alone. A 4-day administration of L-NAME, similarly to acute injection s, decreased the protective action of phenobarbital but not that of di phenylhydantoin. The results indicate that L-NAME is able to reduce th e protective activity of some conventional antiepileptics and this eff ect may be not associated with impaired synthesis of nitric oxide.