Dystonia induced by combined treatment with L-dopa and MK-801 in parkinsonian monkeys.
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.
Rupniak
N M
NM
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
Boyce
S
S
Steventon
M J
MJ
Iversen
S D
SD
Marsden
C D
CD
D000818:Animals; D016291:Dizocilpine Maleate / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D004357:Drug Synergism; D004421:Dystonia / Q000139:chemically induced* / Q000503:physiopathology; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D012016:Reference Values; D012453:Saimiri
D004338:Drug Combinations; D007980:Levodopa; D016291:Dizocilpine Maleate