De novo administration of ropinirole and bromocriptine induces less dyskinesia than L-dopa in the MPTP-treated marmoset.
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.
Pearce
R K
RK
Neurodegenerative Diseases Research Centre, Biomedical Sciences Division, King's College , London, England.
Banerji
T
T
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology*; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D009460:Neurologic Examination / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000503:physiopathology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology
D000978:Antiparkinson Agents; D007211:Indoles; D017448:Receptors, Dopamine D2; C046649:ropinirole; D001971:Bromocriptine; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine