Levodopa-induced dyskinesias in parkinsonian monkeys: relationship to extent of nigrostriatal damage.
The relationship between severity of dopa-induced parkinsonian symptoms and the latency and severity of dopa-induced dyskinesias was studied in monkeys exposed to the toxin MPTP. Levodopa and D-2 receptor agonist-induced dyskinesias appeared early, between 2 and 12 days after initiation of dopa therapy in severely parkinsonian animals. In these animals, it was difficult to find a dose of L-dopa which had beneficial effects clinically and no dyskinesia-producing effects. These animals were all found to have massive (greater than or equal to 95%) striatal dopamine loss. A monkey with mild parkinsonian symptoms never developed dyskinesias similar to those produced in the severely affected animals. Stereotypies could be induced in this animal with excessively high doses of L-dopa or the dopamine D-2 receptor agonist, LY-171555. These movements were controlled by reducing the drug dose. This animal had less severe striatal dopamine loss (less than 80%) than the former group of monkeys. These results suggest that dopa dyskinesias in parkinsonian monkeys may be related to the extent of damage sustained by the nigrostriatal system.
Schneider
J S
JS
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102-1192.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D015259:Dopamine Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000473:pathology*; D004873:Ergolines / Q000009:adverse effects* / Q000627:therapeutic use; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008252:Macaca fascicularis; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000473:pathology*; D019257:Quinpirole
D015259:Dopamine Agents; D004873:Ergolines; D019257:Quinpirole; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine