NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice

Nitric oxide may be involved in seizure phenomena even though data often seem to be contradictory. This prompted us to study the influence of nitric oxide upon electrically and chemically induced seizures. The effects of nitric oxide synthase inhibitor, NG-nitro-L-arginine (NNA), on pentylenetetrazol-, aminooxyacetic acid-, aminophylline-induced seizures or electroconvulsive shock were evaluated. NNA was applied at 1, 10 and 40 mg/ kg 0.5 and 2.0 h before chemical seizures and at 1 and 40 mg/kg 0.5 and 2.0 h prior to electroconvulsions. The nitric oxide synthase inhibitor (up to 40 mg/ kg) did not affect the susceptibility of mice to pentylenetetrazol, amino-oxyacetic acid or electroconvulsions. However, NNA significantly enhanced the convulsive properties of aminophylline when applied at 40 mg/kg, 0.5 h before the test. The CD50 value for aminophylline-induced clonus and tonus/ mortality was decreased from 233 to 191 and from 242 to 212 mg/kg, respectively. However, this pretreatment also led to a significant increase in the plasma levels of theophylline. Our results suggest that differential effects of NNA on chemically-induced convulsions might in some cases be associated with a pharmacokinetic interaction.