Effects of ropinirole on various parkinsonian models in mice, rats, and cynomolgus monkeys.
Ropinirole (4-[2-(dipropylamino)ethyl]-2-indolinone monohydrochloride) a nonergoline dopamine receptor agonist with high affinity for native dopamine D(2)-like receptors in human caudate tissue, was tested with respect to the stimulation of postsynaptic brain dopamine receptors in standard preclinical models of Parkinson's disease. Additionally, in these animal models the antiparkinsonian activity of ropinirole was compared to that of bromocriptine. The ED(50)s (95% confidence limits) of ropinirole and bromocriptine on the turning behavior in 6-OHDA-lesioned rats were 20.17 mg/kg (14.27-26.88 mg/kg) and 11.99 mg/kg (9.37-14.17 mg/kg), respectively. The ED(50)s (95% confidence limits) of ropinirole and bromocriptine on the catalepsy induced by reserpine were 18.55 mg/kg (15.29-22.99 mg/kg) and 12.56 mg/kg (10.25-14.64 mg/kg), respectively. Ropinirole and bromocriptine had no effect on the tremors induced by oxotremorine in mice, whereas atropine markedly suppressed the tremors. The ED(50)s (95% confidence limits) of ropinirole and bromocriptine on the tremors in VMT-lesioned monkeys were 0.18 mg/kg (0.12-0.29 mg/kg) and 2.63 mg/kg (1.06-6.45 mg/kg), respectively. In rodent parkinsonian models, bromocriptine was more potent than ropinirole; however, in the nonhuman primate parkinsonian model, ropinirole was a more potent inhibitor of parkinsonian activity than bromocriptine. 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., Kagoshima, Japan.
Kamenosono
T
T
Nagata
R
R
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001971:Bromocriptine / Q000627:therapeutic use; D002375:Catalepsy / Q000188:drug therapy; D018491:Dopamine Agonists / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D014202:Tremor / Q000188:drug therapy
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007211:Indoles; C046649:ropinirole; D001971:Bromocriptine; D012110:Reserpine; D016627:Oxidopamine