Activities of 7-nitroindazole and 1-(2-(trifluoromethylphenyl)-imidazole independent of neuronal nitric-oxide synthase inhibition

作者：Matsumura Nobuko; Kikuchi Utsumi Kazue; Nakaki Toshio^*

来源：Journal of Pharmacology and Experimental Therapeutics, 2008, 325(2): 357-362.

DOI：10.1124/jpet.107.135160

7-Nitroindazole( NI) is a widely used inhibitor of neuronal nitricoxide synthase ( nNOS) used to study the role of the neuronal NO pathway in the nervous system. 7-NI prevents convulsions, including 2-amino-4-methylphosphinobutyric acid ( glufosinate)induced convulsions, in experimental models. Herein, we examined nNOS involvement in glufosinate-induced convulsions and the specificity of 7- NI for nNOS. Another nNOS inhibitor, 1-[2-(trifluoromethyl) phenyl] imidazole ( TRIM), inhibited NOS activity in vivo, and it prevented glufosinate- induced convulsions. In contrast, an endothelial NOS inhibitor, N5-(1-iminoethyl)-L-ornithine, inhibited NOS activity in vivo, but it did not prevent the convulsions. These results suggest the involvement of nNOS in glufosinate-induced convulsions. However, a nonspecific NOS inhibitor, N-omega- nitro-L-arginine methyl ester, inhibited NOS activity in vivo, but it failed to prevent glufosinate-induced convulsions. 6-NI and indazole, which did not inhibit NOS activity in vivo, suppressed glufosinate-induced convulsions. Moreover, glufosinate elicited convulsions in nNOS-deficient mice. These results suggest the anticonvulsant effects of 7-NI and TRIM on glufosinate-induced convulsions do not involve nNOS inhibition, instead possibly being related to an undefined property of nitrogen-containing chemical structures.

• 出版日期2008-5