Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey parkinsonism.
Quantitative measures for the severity of MPTP-induced parkinsonism and response to antiparkinsonian interventions in monkeys have been lacking. We carried out an oral levodopa dose-response study in two rhesus monkeys whose left hemiparkinsonism was induced by intracarotid administration of MPTP. A newly developed clinical rating scale of monkey parkinsonism showed a consistent dose-response relationship for levodopa over the dosage range of 50-3,500 mg/day. Antiparkinsonian effects appeared at 200 mg/day and were optimal at 1,000-2,000 mg/day. Levodopa also reversed rotational behavior, improved movement times for both the impaired and opposite upper limb, and produced dyskinesias at high dosages. Thus, MPTP-induced hemiparkinsonism in monkeys closely resembles the human disease condition, is associated with sensitive response measures, and should prove valuable for assessing novel antiparkinsonian therapies.
Kurlan
R
R
Department of Neurology, University of Rochester School of Medicine, NY 14642.
Kim
M H
MH
Gash
D M
DM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents; D002230:Carbidopa / Q000008:administration & dosage* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007980:Levodopa / Q000008:administration & dosage* / Q000633:toxicity; D008253:Macaca mulatta; D009460:Neurologic Examination / Q000379:methods / Q000662:veterinary*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D013239:Stereotyped Behavior / Q000187:drug effects
D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002230:Carbidopa