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 result from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridinium metabolite MPP+. Treatment with 7-nitroindazole (7-NI) protects rodents and baboons against MPTP's neurotoxicity, presumably as a consequence of its inhibition of neuronal nitric oxide synthase (nNOS). The results reported in the present communication, while not in conflict with the proposed role of nNOS, raise the possibility that the inhibition of MAO-B by 7-NI also may contribute to the observed neuroprotection.
Castagnoli
K
K
Department of Chemistry, Virginia Tech, Blacksburg 24061-0212, USA. kcastagnoli@chemserver.chem.vt.edu
Palmer
S
S
Anderson
A
A
Bueters
T
T
Castagnoli
N
N
D000818:Animals; D002384:Catalysis; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction
D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; D008995:Monoamine Oxidase; C080122:7-nitroindazole