The effect of N-nitro-L-arginine methyl ester posttreatment on the anticonvulsant effect of phenobarbitone and diazepam on picrotoxin-induced convulsions in rats.

The present study has investigated the effect of posttreatment of the nonspecific inhibitor of nitric oxide (NO) synthase (NOS), N-nitro-L-arginine methyl ester (L-NAME), on the anticonvulsant effect of phenobarbitone and diazepam on picrotoxin-induced convulsions in rats. Phenobarbitone, which is known to inhibit convulsions by potentiating gamma-aminobutyric acid (GABA) activity in the brain, did not inhibit the convulsive action of picrotoxin in L-NAME-posttreated animals. L-NAME produced no such interaction with diazepam, which inhibits convulsions through GABA potentiation as well as by a GABA-independent mechanism. L-arginine, the precursor of NO, increased the protective effect of both phenobarbitone and diazepam. These results suggest that a decreased synthesis of NO in the brain by the nonspecific inhibitors of NOS is likely to result in an impairment of the anticonvulsant effect of antiepileptics that inhibit convulsions solely by potentiating GABA activity in the brain.