L-NAME INHIBITS PENTYLENETETRAZOLE AND STRYCHNINE-INDUCED SEIZURES INMICE

Nitric oxide (NO) formation has been shown in many neuronal tissues su bserves a variety of functions. N-Methyl-D-aspartate (NMDA) receptor s timulation which releases nitric oxide and raises cGMP levels, mediate s epileptiform activity induced by various agents. Disinhibition of in hibitory neurotransmitter gamma-aminobutyric acid (GABA) and/or activa tion of NMDA receptor appears to be factors involved in the initiation and generalization of the pentylenetetrazole (PTZ) induced seizures. In the present study, we examined the effects of N-omega-nitro-L-argin ine methylester (L-NAME) which inhibits nitric oxide synthase, on PTZ and strychnine induced seizures in mice. L-NAME (100 mg/kg) significan tly prolonged the onset time of tonic generalized extension without af fecting myoclonic jerks and tonic-clonic convulsions. L-NAME (200 mg/k g) significantly delayed three characteristic behavioral changes inclu ding first myoclonic jerk (FMJ), generalized clonic seizure (GCS) and tonic generalized extension (TGE). The effects of L-NAME were reversed by L-arginine (1000 mg/kg). L-NAME (100 and 200 mg/kg) significantly delayed the onset time of strychnine induced TGE. The effects of both doses of L-NAME were reversed by L-arginine. In conclusion, our result s demonstrate that NO synthase inhibition suppresses the onset time of PTZ and strychnine induced seizures. Under the light of our current k nowledge NO synthase inhibitors seem far away to be considered as a gr oup of antiepileptic drugs. On the other hand there are some strong ev idences about the role of NO in central pathophysiological mechanisms. (C) 1997 Elsevier Science B.V.