MK-801 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in primates.
In cynomologus monkeys, systemic administration of MK-801, a noncompetitive antagonist for the N-methyl-D-aspartate receptor, prevented the development of the parkinsonian syndrome induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MK-801 also attenuated dopamine depletion in the caudate and putamen and protected dopaminergic neurons in the substantia nigra from the degeneration induced by the neurotoxin. Nevertheless, 7 days after MPTP administration in the caudate and putamen of monkeys also receiving MK-801, the levels of toxic 1-methyl-4-phenylpyridinium were even higher than those measured in monkeys receiving MPTP alone. This indicates that the protective action of MK-801 is not related to MPTP metabolism and strongly suggests that, in primates, the excitatory amino acids could play a crucial role in the mechanism of the selective neuronal death induced by MPTP.
Zuddas
A
A
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Oberto
G
G
Vaglini
F
F
Fascetti
F
F
Fornai
F
F
Corsini
G U
GU
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D011699:Putamen / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects
D016291:Dizocilpine Maleate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine