Meller E, Bohmaker K, Goldstein M, Schweitzer J W, Friedhoff A J
Eur J Pharmacol. 1985 Mar 12;109(3):389-94. doi: 10.1016/0014-2999(85)90400-5.
Agonist competition for [3H]spiperone binding to striatal dopamine D2 receptors was studied in rats rendered supersensitive by chronic treatment with haloperidol. The classical dopamine agonist (-)-N-n-propylnorapomorphine displaced [3H]spiperone biphasically, with IC50 values of 0.5 and 140 nM for the high and low affinity components, respectively. Neither the relative density nor the affinity of either site for (-)-N-propylnorapomorphine was affected by chronic haloperidol treatment. On the other hand, the novel agonist EMD 23 448 displaced [3H]spiperone monophasically. Although this agent only displays potent dopaminergic agonism in supersensitive animals, chronic treatment with haloperidol likewise did not alter the affinity of this drug for [3H]spiperone binding sites. The results suggest that the enhanced in vivo potency of certain agonists in supersensitive animals is probably not mediated by changes in D2 receptor affinity.
研究了在经氟哌啶醇长期治疗而变得超敏的大鼠中，激动剂对[3H]螺哌隆与纹状体多巴胺D2受体结合的竞争情况。经典多巴胺激动剂（-）-N-正丙基去甲阿朴吗啡对[3H]螺哌隆的置换呈双相性，高亲和力和低亲和力组分的IC50值分别为0.5和140 nM。慢性氟哌啶醇治疗对任一部位对（-）-N-丙基去甲阿朴吗啡的相对密度或亲和力均无影响。另一方面，新型激动剂EMD 23 448对[3H]螺哌隆的置换呈单相性。尽管该药物仅在超敏动物中表现出强效多巴胺能激动作用，但慢性氟哌啶醇治疗同样未改变该药物对[3H]螺哌隆结合位点的亲和力。结果表明，某些激动剂在超敏动物中体内效力增强可能并非由D2受体亲和力的变化介导。
