Effects of ropinirole on motor behavior in MPTP-treated common marmosets.
The effects of ropinirole (4-[2-(dipropylamino)ethyl]-2-indolinone monohydrochloride), a nonergoline dopamine receptor agonist with a high affinity for native dopamine D(2)-like receptors, on Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2.5 mg/animal in common marmosets were examined and compared to the effects of bromocriptine. Ropinirole (0.1-3 mg/kg, PO) increased motor activity dose dependently and reversed akinesia or uncoordinated movement in MPTP-treated marmosets. The activities for ropinirole were very similar to those of bromocriptine. Ropinirole had, however, several properties that differed from those of bromocriptine. Ropinirole caused a more rapid onset of anti-Parkinsonian activity compared to bromocriptine, and had a potency more than five times greater than that of bromocriptine in the improvement of motor deficits. The combination of ropinirole and L-DOPA increased the effectiveness of ropinirole or L-DOPA alone, and produced a more marked additive effect on motor activity than did bromocriptine and L-DOPA. Chronic administration of ropinirole for 21 days produced a statistically significant increase in motor activity compared to the initial administration, and akinesia scores, measured through rating the quality of movements, were also improved without obvious dyskinesia. This study suggests that ropinirole is a dopamine D(2)-like receptor agonistic drug of potential use in the treatment of Parkinson's disease.
Fukuzaki
K
K
Shin Nippon Biomedical Laboratories Ltd., 2438 Miyanoura, 891-1394, Kagoshima, Japan.
Kamenosono
T
T
Kitazumi
K
K
Nagata
R
R
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D002144:Callithrix; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D050637:Receptors, Dopamine D3
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007211:Indoles; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C046649:ropinirole; D001971:Bromocriptine; D007980:Levodopa