Pargyline Prevents MPTP-Induced Parkinsonism in Primates

• Published in: Science (American Association for the Advancement of Science) Vol. 225; no. 4669; pp. 1480 - 1482
• Main Authors: Langston, J. William, Irwin, Ian, Langston, Elizabeth B., Forno, Lysia S.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 28.09.1984; American Association for the Advancement of Science
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Brain Chemistry; Dosage; Male; Medical sciences; Monoamine oxidase; Monoamine oxidase inhibitors; Neurons; Neurons - pathology; Neuropharmacology; Neurotoxic agents; Neurotoxicity; Pargyline - pharmacology; Pargyline - therapeutic use; Parkinson disease; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - pathology; Parkinson Disease, Secondary - prevention & control; Parkinsonian disorders; Parkinsonism; Pharmacology. Drug treatments; Primates; Pyridines - analysis; Pyridines - metabolism; Pyridines - toxicity; Pyridinium Compounds - analysis; Pyridinium Compounds - metabolism; Saimiri; Serotonin syndrome; Substantia nigra; Substantia Nigra - pathology; Nervous system diseases; Monoamine oxidase; Toxicity; Monkey; Enzyme inhibitor; Parkinson disease; Antiparkinson agent; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Neurotoxin; Primates; Drug of abuse; Mechanism of action
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.6332378

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys with pargyline, a monoamine oxidase (MAO) inhibitor, prevents both clinical and neuropathological evidence of the neurotoxic effects of MPTP. Pargyline also inhibits conversion of MPTP to 1-methyl-4-phenylpyridinium ion (MPP$^{+}$), a metabolic step that occurs rapidly after administration of MPTP in animals not treated with pargyline. It is proposed that the conversion of MPTP to MPP$^{+}$, possibly involving MAO, may be important for the neurotoxic effects of MPTP to take place, and MPTP itself may not be the neurotoxic agent.