Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors
Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors
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DOI：
10.1016/s0014-2999(98)00896-6
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发表时间：
1999-02-05
影响因子：
5
通讯作者：
Sokoloff, P
中科院分区：
文献类型：
--
作者：
Perachon, S;Schwartz, JC;Sokoloff, P
我们在结合和功能测试中测量了溴隐亭、普拉克索、培高利特和罗匹尼罗对人类重组多巴胺D-1、D-2和D-3受体的亲和力。所有四种化合物都与多巴胺D-3受体具有高亲和力;溴隐亭和培高利特对多巴胺D-2受体也具有高亲和力，而只有培高利特对多巴胺D-1受体具有显著的亲和力，尽管中等。只有培高利特对多巴胺D-1受体具有高效力和内在活性，可刺激环AMP蓄积。此外，培高利特和溴隐亭以及多巴胺在多巴胺D-1受体上的效力和功效在存在腺苷酸环化酶激活剂毛喉素的情况下增加。所有四种化合物都是多巴胺D-2和D-3受体的高效激动剂，如在有丝分裂试验中所测量的。与多巴胺D-3受体相比，溴隐亭对多巴胺D-2的效力高10倍，而普拉克索和罗匹尼罗对多巴胺D-3受体的效力低10倍，而培高利特对这两种受体的效力相等。这些结果表明，最近开发的抗帕金森病药物在多巴胺D-1或多巴胺D-3，而不仅仅是多巴胺D-2受体的活性应考虑在分析其治疗作用机制。(C)1999 Elsevier Science B. V.保留所有权利。
We measured the affinities of bromocriptine, pramipexole, pergolide and ropinirole at human recombinant dopamine D-1, D-2 and D-3 receptors in binding and functional tests. All four compounds bound with high affinity at the dopamine D-3 receptor; bromocriptine and pergolide also had high affinity for the dopamine D-2 receptor, while only pergolide had significant, although moderate, affinity for the dopamine D-1 receptor. Only pergolide had high potency and intrinsic activity at the dopamine D-1 receptor for stimulating cyclic AMP accumulation. In addition, the potencies and efficacies of pergolide and bromocriptine, as well as that of dopamine, at the dopamine D-1 receptor were increased in the presence of forskolin, an adenylate cyclase activator. All four compounds were highly potent agonists at dopamine D-2 and D-3 receptors, as measured in a mitogenesis assay. Bromocriptine was ten times more potent and pramipexole and ropinirole ten times less potent at the dopamine D-2 than at the dopamine D-3 receptor, whereas pergolide was equipotent at the two receptors. These results suggest that the activity of recently developed antiparkinsonian drugs at either the dopamine D-1 or the dopamine D-3 and not only the dopamine D-2 receptors should be taken into account in analyses of their mechanisms of action in therapeutics. (C) 1999 Elsevier Science B.V. All rights reserved.