[Comparative studies on antiparkinsonian agents, talipexole and bromocriptine, evaluated by contralateral rotational behavior in unilaterally nigral-lesioned rats].
The stimulating effect of antiparkinsonian drugs, talipexole and bromocriptine, on the striatal postsynaptic dopamine receptors were studied by measuring contralateral rotational behavior in rats. The nigro-striatal dopamine system of rats was degenerated by unilateral injection of 6-hydroxydopamine (6-OHDA, 8 micrograms/rat) into substantia nigra. By subcutaneous administration, talipexole at 0.16 mg/kg and bromocriptine at 10.24 mg/kg induced significantly increased rotational behavior to the contralateral direction to the lesioned side. The onset of the effect was 30 min for talipexole and 90 min for bromocriptine. By intragastric administration, talipexole at 0.4 mg/kg and bromocriptine at 20.48 mg/kg significantly increased the rotational behavior, and the onset of the effect was 60 min for talipexole and 180 min for bromocriptine. Rotational behavior induced by talipexole was suppressed by a D2 antagonist, sulpiride (40 mg/kg, s.c.), but not by a D1 antagonist, SCH23390 (1 mg/kg, s.c.). In contrast, rotational behavior induced by bromocriptine was suppressed by both sulpiride and SCH23390. These results indicated that when the nigrostriatal dopaminergic functions are disrupted, talipexole stimulates the striatal postsynaptic dopamine receptors at much lower doses than bromocriptine. Also it was indicated that the stimulating effect of talipexole is solely mediated by dopamine D2 receptors, whereas the effect of bromocriptine is mediated by both D1 and D2 receptors.
Hironaka
N
N
Preclinical Research Laboratories Inc., Kanagawa, Japan.
Kohno
Y
Y
Yanagita
T
T
D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
D000978:Antiparkinson Agents; D001381:Azepines; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; C024763:talipexole; D013469:Sulpiride; D016627:Oxidopamine