Clemens J A, Okimura T, Smalstig E B
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
Arzneimittelforschung. 1993 Mar;43(3):281-6.
Four pergolide metabolites and bromocriptine (CAS 25614-03-3) were compared to pergolide (8 beta-[(methylthio) methyl]-6-propyl-ergoline, CAS 66104-22-1) using three in vivo animal models of activity at dopamine receptors. The results obtained from these studies of prolactin inhibition, induction of compulsive turning, and stimulation of stereotypic behavior, were very consistent. Two of the metabolites, despropyl pergolide and despropyl pergolide sulfoxide, were devoid of dopamine-like effects in any of the models. Pergolide sulfone and pergolide sulfoxide, however, were found to be potent dopamine agonists, similar in activity to pergolide itself. Dopamine D2 receptors (and probably D1 receptors also) appear to be involved in the activities of these compounds. The compounds were active by both oral and i.p. routes of administration. Bromocriptine, while possessing some dopamine agonist activity at higher doses in some of these animal models, was much less potent (1/200 to 1/20) than either pergolide or its two dopaminergic metabolites.
使用三种多巴胺受体活性的体内动物模型，将四种培高利特代谢物与溴隐亭（CAS 25614-03-3）与培高利特（8β-[(甲硫基)甲基]-6-丙基-麦角林，CAS 66104-22-1）进行比较。这些关于催乳素抑制、强迫性旋转诱导和刻板行为刺激的研究结果非常一致。其中两种代谢物，去丙基培高利特和去丙基培高利特亚砜，在任何模型中都没有多巴胺样作用。然而，培高利特砜和培高利特亚砜被发现是强效多巴胺激动剂，其活性与培高利特本身相似。多巴胺D2受体（可能还有D1受体）似乎参与了这些化合物的活性。这些化合物通过口服和腹腔注射途径给药均有活性。溴隐亭虽然在某些动物模型中高剂量时具有一些多巴胺激动剂活性，但其效力比培高利特或其两种多巴胺能代谢物低得多（1/200至1/20）。
