NG-nitro-L-arginine sensitizes mice to 4-aminopyridine-induced seizures.

We investigated the influence of NG-nitro-L-arginine (NNA), the inhibitor of nitric oxide synthese, on seizures induced by 4-aminopyridine (4-AP), the K+ channel antagonist, in mice NNA (5, 10 and 40 mg/kg, i.p.) significantly reduced the respectives CD50 of 4-AP from 9.0 to 7.6, 7.5 and 6.8 for clonic seizures, and from 9.2 to 7.7, 7.5 and 6.9 for tonic seizures and death. Lower doses of NNA (1.0 and 2.5 mg/kg) had no effect on 4-AP-induced convulsions and lethality. Our results indicate that 4-AP-induced seizures may be, at least in part, dependent on nitric oxide level.