L-NAME inhibits pentylenetetrazole and strychnine-induced seizures in mice.
Nitric oxide (NO) formation has been shown in many neuronal tissues subserves a variety of functions. N-Methyl-D-aspartate (NMDA) receptor stimulation which releases nitric oxide and raises cGMP levels, mediates epileptiform activity induced by various agents. Disinhibition of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and/or activation 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-arginine methylester (L-NAME) which inhibits nitric oxide synthase, on PTZ and strychnine induced seizures in mice. L-NAME (100 mg/kg) significantly prolonged the onset time of tonic generalized extension without affecting myoclonic jerks and tonic-clonic convulsions. L-NAME (200 mg/kg) significantly delayed three characteristic behavioral changes including 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 results demonstrate that NO synthase inhibition suppresses the onset time of PTZ and strychnine induced seizures. Under the light of our current knowledge NO synthase inhibitors seem far away to be considered as a group of antiepileptic drugs. On the other hand there are some strong evidences about the role of NO in central pathophysiological mechanisms.
Kaputlu
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Department of Pharmacology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
Uzbay
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D000818:Animals; D003292:Convulsants / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013331:Strychnine / Q000037:antagonists & inhibitors
D003292:Convulsants; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D013331:Strychnine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole