MK‐801 Prevents 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Induced Parkinsonism in Primates

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Abstract
In cynomologus monkeys, systemic administration of MK‐801, a noncompetitive antagonist for the N‐methyl‐4‐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 l‐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.