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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Animals
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Disease Models, Animal
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Dopamine / metabolism
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Enzyme Inhibitors / pharmacology*
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Homovanillic Acid / metabolism
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Hypokinesia
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Indazoles / pharmacology*
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Male
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Motor Activity
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Neurologic Examination
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Neurons / drug effects
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Neurons / enzymology*
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase / metabolism
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Papio
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Parkinson Disease, Secondary / chemically induced
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Parkinson Disease, Secondary / drug therapy*
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Parkinson Disease, Secondary / enzymology
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Substantia Nigra / drug effects
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Substantia Nigra / enzymology
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Videotape Recording
Substances
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Enzyme Inhibitors
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Indazoles
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3,4-Dihydroxyphenylacetic Acid
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Nitric Oxide Synthase
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7-nitroindazole
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Dopamine
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Homovanillic Acid