Influence of 7-nitroindazole on the anticonvulsive action of conventional antiepileptic drugs.

7-Nitroindazole (a selective neuronal nitric oxide (NO) synthase inhibitor) at 25 and 50 mg/kg, 30 min before the test, did not influence the electroconvulsive threshold. However, at 50 mg/kg, it enhanced the anticonvulsive activity of phenobarbital against maximal electroshock and did not affect that of carbamazepine, diphenylhydantoin and valproate. L-Arginine (500 mg/kg) did not modify the protective activity of phenobarbital alone or the 7-nitroindazole-induced enhancement of its anticonvulsive potency against maximal electroshock. 7-Nitroindazole did not alter the plasma levels of antiepileptic drugs, so a pharmacokinetic interaction, in terms of total and free plasma levels, is not probable. 7-Nitroindazole combined with the antiepileptics resulted in motor disturbances, except for the combination with phenobarbital. On the other hand, the combined treatment of 7-nitroindazole with carbamazepine or phenobarbital produced effects superior to those produced by single drugs, as regards long-term memory. Our results indicate that the protective activity of carbamazepine, diphenylhydantoin, or valproate against maximal electroshock may be not dependent upon the central NO level. The enhancement of the anticonvulsive action of phenobarbital by 7-nitroindazole is probably not related to the decrease of NO in the central nervous system.