Hironaka N, Kohno Y, Yanagita T
Preclinical Research Laboratories Inc., Kanagawa, Japan.
Nihon Yakurigaku Zasshi. 1998 Oct;112(4):257-66. doi: 10.1254/fpj.112.257.
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.
通过测量大鼠的对侧旋转行为,研究了抗帕金森病药物他利克索和溴隐亭对纹状体突触后多巴胺受体的刺激作用。通过向大鼠黑质单侧注射6-羟基多巴胺(6-OHDA,8微克/只)来破坏大鼠的黑质-纹状体多巴胺系统。皮下给药时,0.16毫克/千克的他利克索和10.24毫克/千克的溴隐亭可显著增加向损伤侧对侧方向的旋转行为。他利克索的起效时间为30分钟,溴隐亭为90分钟。胃内给药时,0.4毫克/千克的他利克索和20.48毫克/千克的溴隐亭可显著增加旋转行为,他利克索的起效时间为60分钟,溴隐亭为180分钟。他利克索诱导的旋转行为可被D2拮抗剂舒必利(40毫克/千克,皮下注射)抑制,但不能被D1拮抗剂SCH23390(1毫克/千克,皮下注射)抑制。相比之下,溴隐亭诱导的旋转行为可被舒必利和SCH23390两者抑制。这些结果表明,当黑质-纹状体多巴胺能功能被破坏时,他利克索刺激纹状体突触后多巴胺受体所需的剂量比溴隐亭低得多。还表明他利克索的刺激作用仅由多巴胺D2受体介导,而溴隐亭的作用由D1和D2受体两者介导。