Dyskinesia and wearing-off following dopamine D1 agonist treatment in drug-naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates.
The motor effects of the short-acting, full D1 agonist SKF 82958 were studied in three drug-naive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned, parkinsonian monkeys treated for 4 weeks. D1 receptor stimulation with SKF 82958 effectively relieved parkinsonism but induced choreic dyskinesia (n = 2) and a shorter duration of motor benefit (n = 3) over time. Isolated, short-lived D1 receptor activation would not appear to confer advantage over levodopa for dyskinesia prevention. Our data also support the involvement of postsynaptic dopamine receptor mechanisms in the wearing-off phenomenon seen in levodopa-treated parkinsonian patients.
Blanchet
P J
PJ
Neurobiology Research Centre, Hôpital de l'Enfant-Jésus, Québec City, Canada.
Grondin
R
R
Bédard
P J
PJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D009460:Neurologic Examination / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology
D001552:Benzazepines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D007980:Levodopa; C071262:SK&F 82958; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine