Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons

Abstract

1–Methyl–4–phenyl–1,2/3,6–tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7–Nitroindazole (7–NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase (NOS) that blocks MPTP neurotoxicity in mice. We now show that 7–NI protects against profound striatal dopamine depletions and loss of tyrosine hydroxylase–positive neurons in the substantia nigra in MPTP–treated baboons. Furthermore, 7–NI protected against MPTP–induced motor and frontal–type cognitive deficits. These results strongly implicate a role of nitric oxide in MPTP neurotoxicity and suggest that inhibitors of neuronal NOS might be useful in treating Parkinson's disease.

Cite this article

Hantraye, P., Brouillet, E., Ferrante, R. et al. Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons. Nat Med 2, 1017–1021 (1996). https://doi.org/10.1038/nm0996-1017

View full text

>> Full Text:   Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons