Anticonvulsant activity of new and potent inhibitors of nitric oxide synthase.
The effects of new and potent NOS inhibitors, S-methyl-L-thiocitrulline (S-Me-TC), 3-bromo 7-nitro indazole (3-Br-7-NI), and 1-(2-trifluoromethylphenyl) imidazole (TRIM), were examined on the pilocarpine-induced seizures in mice. 3-Br-7-NI and TRIM decreased the frequency of status epilepticus and mortality, while TRIM. In addition, significantly reduced the incidence of seizures. The latencies to onsets of seizures, status epilepticus, and mortality were significantly prolonged by all three NOS inhibitors, while duration of seizures was reduced by 3-Br-7-NI and TRIM. These data suggest an excitatory effect of NO in the neuronal structure involved in the pilocarpine-induced seizures.
Dzoljic
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Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
De Vries
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Dzoljic
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D007093:Imidazoles; D002956:Citrulline; C029899:imidazole; D019001:Nitric Oxide Synthase; D013890:Thiourea; C086717:S-methylthiocitrulline