De novo administration of ropinirole and bromocriptine induces less dyskinesia than L‐dopa in the MPTP‐treated marmoset

Abstract

In contrast to levodopa (L‐dopa), de novo administration of the D2‐like receptor agonist bromocriptine to patients with Parkinson's disease (PD) or to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated subhuman primates is not associated with the onset of significant dyskinesia. We now compare the ability of the novel D2‐like selective dopamine agonist ropinirole with that of bromocriptine and L‐dopa to induce dyskinesia in MPTP‐treated common marmosets. MPTP‐treated common marmosets were treated with placebo, L‐dopa plus carbidopa, ropinirole, or bromocriptine daily for 30 days (n = 4 per group) in doses that were titrated to similarly increase locomotion and improve motor disability. L‐dopa rapidly induced dyskinesia of moderate to severe intensity, whereas ropinirole and bromocriptine produced mild dyskinesia over the course of the study that was significantly less severe than in the L‐dopa‐treated group (p < 0.05). However, in a separate group of marmosets previously primed with L‐dopa to exhibit dyskinesia, ropinirole administration elicited severe dyskinesias comparable with that of L‐dopa in a dosedependent fashion. Ropinirole, in common with bromocriptine, has a lesser tendency than L‐dopa to produce dyskinesia while similarly improving motor performance in drug‐naive MPTP‐treated marmosets. However, in common with other dopamine agonists, ropinirole will elicit comparable dyskinesia once L‐dopa priming has occurred. These results predict a similar response to ropinirole and other long‐acting dopamine agonists in L‐dopa‐naive patients with PD and emphasize the importance of avoiding initial dyskinesia induction through early use of dopamine agonist drugs.