Dopamine-receptor families and the treatment of Parkinson's disease

A series of experiments were performed in the MPTP (n-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) monkey model of parkinsonism to identify the role of specific dopamine receptors in the therapeutic response and in the production of dyskinesia, one of the main side effects of antiparkinsonian treatment. In the first series of experiments, selective agonists of D₁ or D₂ receptors were administered to parkinsonian monkeys previously treated with L-dopa that had developed prominent dyskinesia. Both D₁ and D₂ agonists displayed good antiparkinsonian efficacy, but D₁ agonists were much less likely to reproduce the dyskinesia. In the second group of experiments, drug-naive MPTP monkeys were treated chronically with a single dopaminergic agent acting on either the D₁- or the D₂-receptor family. Both types of agonists, particularly the short-acting D₂ agonists administered continuously by minipump, were less dyskinetogenic.