INHIBITION OF NEURONAL NITRIC-OXIDE SYNTHASE PREVENTS MPTP-INDUCED PARKINSONISM IN BABOONS

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which oc cur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a rel atively selective inhibitor of the neuronal isoform of nitric oxide sy nthase (NOS) that blocks MPTP neurotoxicity in mice. We now show that 7-NI protects against profound striatal dopamine depletions and loss o f tyrosine hydroxylase-positive neurons in the substantia nigra in MPT P-treated baboons. Furthermore, 7-NI protected against MPTP-induced mo tor and frontal-type cognitive deficits. These results strongly implic ate a role of nitric oxide in MPTP neurotoxicity and suggest that inhi bitors of neuronal NOS might be useful in treating Parkinson's disease .