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. (C) 1997 Elsevier Science Inc.