Antiparkinsonian activity and dyskinesia risk of ropinirole and L-DOPA combination therapy in drug naïve MPTP-lesioned common marmosets (Callithrix jacchus).
De novo administration of long-acting dopamine agonists, such as ropinirole, to patients with Parkinson's disease or to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated subhuman primates produces a lower incidence of dyskinesia than occurs with L-DOPA. This study compares the intensity of dyskinesia produced by combinations of L-DOPA and ropinirole and by these drugs alone, using the MPTP-treated common marmoset model of Parkinson's disease. The objective is to determine the optimum therapeutic strategy for the long-term control of Parkinson's disease with a minimal risk of dyskinesia. MPTP-treated marmosets received either L-DOPA alone, ropinirole alone, or one of two combinations of these drugs (either L-DOPA dominant or ropinirole dominant) daily for 28 days in doses titrated to produce a similar improvement in disability and increase in locomotion. In the group receiving L-DOPA alone, there was a trend for peak dose locomotor activity to increase and the duration of drug effect to decline over the period of the study. L-DOPA alone induced marked dyskinesia over the period of treatment, in contrast to ropinirole which produced a low intensity of involuntary movements. The L-DOPA dominant combination initially produced little dyskinesia, but this became increasingly intense as the study progressed. In contrast, the ropinirole dominant combination produced no greater intensity of dyskinesia than was produced by ropinirole alone. These data suggest that in early Parkinson's disease, the use of ropinirole alone or in combination with a low-dose L-DOPA might delay the induction of dyskinesias while improving motor performance.
Maratos
E C
EC
Neurodegenenerative Disease Research Centre, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College, London, United Kingdom.
Jackson
M J
MJ
Pearce
R K
RK
Jenner
P
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D009460:Neurologic Examination / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000188:drug therapy*
D000978:Antiparkinson Agents; D007211:Indoles; C046649:ropinirole; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine