Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum
Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum
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DOI：
10.1007/s00702-003-0027-5
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发表时间：
2003-10-01
影响因子：
3.3
通讯作者：
Riederer, P
中科院分区：
文献类型：
--
作者：
Gerlach, M;Double, K;Riederer, P
本研究的目的是比较所有目前批准的多巴胺受体激动剂治疗人类脑组织中帕金森病（PD）的多巴胺受体结合亲和力。与D-1/D-2多巴胺激动剂培高利特（Ki = 447 nM）相比，α-二氢麦角碱和麦角脲对D-1受体显示出更高的相对亲和力（Ki = 35.4和56.7 nM）。第二代非麦角类多巴胺受体激动剂普拉克索和罗匹尼罗在浓度高达10（-4）M时对D1受体无亲和力。麦角林多巴胺激动剂卡麦角林和麦角脲对D-2受体表现出最高的亲和力（Ki分别为0.61和0.95 nM）。令人惊讶的是，第二代非麦角多巴酚宁受体激动剂普拉克索和罗匹尼罗仅微弱地抑制与D2受体的结合（使用[H-3]雷氯必利时，Ki分别为79.5和98.7 μ M）。有趣的是，我们还发现卡麦角林（Ki = 1.27 nM）、麦角脲（Ki = 1.08 nM）和培高利特（Ki = 0.86 nM）对D-3受体亚型的亲和力与普拉克索（Ki = 0.97 nM）相当。因此，本研究结果支持的假设，多巴胺受体激动剂的抗帕金森病的效果是由一个更复杂的相互作用介导的多巴胺受体亚型比目前认为的。
The aim of this study was to compare dopamine receptor binding affinities of all currently approved dopamine receptor agonist treatments for Parkinson's disease (PD) in human brain tissue. alpha-Dihydroergoeryptine and lisuride displayed higher comparative affinities (K-i = 35.4 and 56.7 nM, respectively) for D-1 receptors, than the D-1/D-2 dopamine agonist pergolide (Ki = 447 nM). The second generation non-ergot dopamine receptors agonists pramipexole and ropinirole demonstrated no affinity for D, receptors at concentrations up to 10(-4) M. The ergoline dopamine agonists cabergoline and lisuride displayed the highest affinities for the D-2 receptor (K-i = 0.61 and 0.95 nM, respectively). Surprisingly, the second generation non-ergot doparnine receptors agonists pramipexole and ropinirole only weakly inhibited binding to D2 receptors (K-i = 79.5 and 98.7 muM, respectively using [H-3]raclopride). Interestingly we also found that the affinities of cabergoline (K-i = 1.27 nM), lisuride (K-i = 1.08 nM) and pergolide (K-i = 0.86 nM) for the D-3 receptor subtype were comparable to that of pramipexole (K-i = 0.97 nM). The present results thus support the hypothesis that the antiparkinsonian effect of dopamine receptor agonists is mediated by a more complex interactions with dopamine receptor subtypes than currently believed.