THE NEURONAL NITRIC-OXIDE SYNTHASE INHIBITOR 7-NITROINDAZOLE ALSO INHIBITS THE MONOAMINE OXIDASE-B-CATALYZED OXIDATION OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE

The neurodegenerative properties of the parkinsonian inducing agent 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are thought to resul t from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridini um metabolite MPP+. Treatment with 7-nitroindazole (7-NI) protects rod ents and baboons against MPTP's neurotoxicity, presumably as a consequ ence of its inhibition of neuronal nitric oxide synthase (nNOS). The r esults reported in the present communication, while not in conflict wi th the proposed role of nNOS, raise the possibility that the inhibitio n of MAO-B by 7-NI also may contribute to the observed neuroprotection .