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.