A role of nitric oxide in organophosphate-induced convulsions

The effects of nitric oxide-regulating compounds on convulsions and mortality of rats administered i.p. with diisopropylfluorophosphate was investigated. l-N(G)-nitroarginine methyl ester, a nitric oxide synthase inhibitor possessing an anticholinergic action, markedly attenuated the intensity of convulsions and significantly reduced the mortality rate. A similar result was obtained with anticholinergic procyclidine, an N-methyl-d-aspartate receptor antagonist. Noteworthy, l-N(G)-nitroarginine, another inhibitor of nitric oxide synthase, significantly attenuated the seizure intensity when administered in combination with atropine sulfate (5 mg/kg), though either l-N(G)-nitroarginine or atropine sulfate was inactive alone. It is suggested that nitric oxide may be a proconvulsant or a convulsion-promoting factor in anticholinesterase poisoning, and both the reduction of nitric oxide level and blockade of cholinergic systems may be required for more effective protection of seizures.