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

Mov Disord. 1998 Mar;13(2):234-41. doi: 10.1002/mds.870130207.

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 dose-dependent 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Bromocriptine / pharmacology*
  • Callithrix
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Dyskinesia, Drug-Induced / physiopathology*
  • Female
  • Indoles / pharmacology*
  • Levodopa / pharmacology*
  • Male
  • Motor Skills / drug effects*
  • Motor Skills / physiology
  • Neurologic Examination / drug effects
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / physiopathology
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / physiology

Substances

  • Antiparkinson Agents
  • Indoles
  • Receptors, Dopamine D2
  • ropinirole
  • Bromocriptine
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine