Dystonia induced by combined treatment with L‐dopa and MK‐801 in parkinsonian monkeys

Abstract

We examined whether the N‐methyl‐D‐aspartate antagonist MK‐801 (dizocilpine) would reverse parkinsonism or potentiate the effects of L‐dopa in primates treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In contrast to its effect in rodent models, treatment with MK‐801 (0.1 mg/kg) caused bradykinesia and ataxia in parkinsonian primates, but no locomotor stimulation. Coadministration of MK‐801 (0.1 mg/kg) with L‐dopa (20 mg/kg) induced marked dystonia accompanied by bradykinesia and ataxia. Dystonia was not induced by either treatment given alone. These findings indicate that MK‐801 should not be advocated as an adjunct to dopamine agonist therapy in Parkinson's disease.