Miyagi M, Itoh F, Taya F, Arai N, Isaji M, Kojima M, Ujiie A
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Biol Pharm Bull. 1996 Sep;19(9):1210-3. doi: 10.1248/bpb.19.1210.
An ergot alkaloid derivative, cabergoline, and its metabolites were investigated for their affinities for dopamine D1 and D2 receptors in rat striatum in vitro in comparison with those of bromocriptine and pergolide. The affinity for D1 receptors was in the following order: pergolide > des-dimethylaminopropyl cabergoline (FCE21904) > cabergoline > or = bromocriptine > or = des-methyl cabergoline (FCE27395) > or = des-ethylcarbamoyl cabergoline (FCE21590). From the effects of GTP on these affinities for the D1 receptor, cabergoline, some of its metabolites, and pergolide were characterized as agonists in contrast to bromocriptine which was classified as an antagonist. The affinity for D2 receptors was ranked as follows: pergolide > or = cabergoline > or = FCE27395 > or = FCE21904 > bromocriptine > FCE21590 > carboxylic acid-type derivative of cabergoline (FCE21589). The affinity of each compound for the D2 receptor was much higher than that for the D1 receptor. The selectivity of cabergoline for D2 receptor was higher than those of bromocriptine and pergolide. Furthermore, these ergot alkaloids were investigated for eliciting stereotypy after subcutaneous administration to normal rats. Pergolide potently induced stereotypy at doses of 0.5 and 1.0 mg/kg, cabergoline slightly induced it only at a high dose of 2.0 mg/kg, whereas bromocriptine did not induce it at any of the doses tested, 10-40 mg/kg. These results suggest that pharmacological properties of cabergoline for the D1 and D2 receptors differ from those of bromocriptine and pergolide.
研究了一种麦角生物碱衍生物卡麦角林及其代谢产物与溴隐亭和培高利特相比，在体外对大鼠纹状体中多巴胺D1和D2受体的亲和力。它们对D1受体的亲和力顺序如下：培高利特＞去二甲基氨基丙基卡麦角林（FCE21904）＞卡麦角林＞或 = 溴隐亭＞或 = 去甲基卡麦角林（FCE27395）＞或 = 去乙基氨甲酰基卡麦角林（FCE21590）。从GTP对这些D1受体亲和力的影响来看，卡麦角林、其一些代谢产物和培高利特被表征为激动剂，而溴隐亭则被归类为拮抗剂。对D2受体的亲和力排名如下：培高利特＞或 = 卡麦角林＞或 = FCE27395＞或 = FCE21904＞溴隐亭＞FCE21590＞卡麦角林的羧酸型衍生物（FCE21589）。每种化合物对D2受体的亲和力远高于对D1受体的亲和力。卡麦角林对D2受体的选择性高于溴隐亭和培高利特。此外还研究了这些麦角生物碱皮下注射给正常大鼠后引发刻板行为的情况。培高利特在0.5和1.0 mg/kg剂量时能有效诱导刻板行为，卡麦角林仅在2.0 mg/kg的高剂量时轻微诱导刻板行为，而溴隐亭在测试的任何剂量（10 - 40 mg/kg）下均未诱导刻板行为。这些结果表明，卡麦角林对D1和D2受体的药理特性与溴隐亭和培高利特不同。
