Recent methods for measuring dopamine D3 receptor occupancy in vivo: importance for drug development.
Recent methods for measuring dopamine D3 receptor occupancy in vivo: importance for drug development.
复制标题
测量体内多巴胺D3受体占用率的最新方法：对药物开发的重要性。
DOI：
10.3389/fphar.2014.00161
复制
发表时间：
2014
影响因子：
5.6
通讯作者：
Di Ciano P
中科院分区：
文献类型：
--
作者：
Le Foll B;Wilson AA;Graff A;Boileau I;Di Ciano P
人们对开发用于治疗各种精神健康疾病的高选择性多巴胺 (DA) D3 受体配体非常感兴趣。 DA D3 受体与帕金森病、精神分裂症、焦虑症、抑郁症和药物滥用障碍有关。最具体的证据表明 D3 受体在药物寻求行为中发挥作用。 D3 受体是 D2 受体的一个亚型，传统上很难区分这两种受体的功能作用。在过去的 10-15 年中，开发了许多对 D3 受体选择性高于 D2 受体的化合物。然而，将这些发现转化为临床研究一直很困难，因为其中许多化合物不能用于人类。因此，涉及D3受体在药物成瘾中的功能数据大多来自于临床前研究。最近，随着[11C]-(+)-PHNO的出现，以更高的选择性和灵敏度对人脑中的D3受体进行成像成为可能。与无法区分 D2 和 D3 受体的 [11C]-雷氯必利等传统方法相比，这是一项重大创新。 [11C]-(+)-PHNO 的使用将有助于进一步描述 D3 受体的作用。在这里，我们回顾了最近的证据，表明 D3 受体的作用具有重要的功能，并且与 D2 受体的作用不同。然后我们介绍了按感兴趣区域分析 [11C]-(+)-PHNO 结合的实用性。这种新颖的方法可用于临床前和临床方法中测量 D3 和 D2 受体的占用情况。还提供了 [11C]-(+)-PHNO 可以深入了解 D3 受体在成瘾中的功能的证据。
There is considerable interest in developing highly selective dopamine (DA) D3 receptor ligands for a variety of mental health disorders. DA D3 receptors have been implicated in Parkinson’s disease, schizophrenia, anxiety, depression, and substance use disorders. The most concrete evidence suggests a role for the D3 receptor in drug-seeking behaviors. D3 receptors are a subtype of D2 receptors, and traditionally the functional role of these two receptors has been difficult to differentiate. Over the past 10–15 years a number of compounds selective for D3 over D2 receptors have been developed. However, translating these findings into clinical research has been difficult as many of these compounds cannot be used in humans. Therefore, the functional data involving the D3 receptor in drug addiction mostly comes from pre-clinical studies. Recently, with the advent of [11C]-(+)-PHNO, it has become possible to image D3 receptors in the human brain with increased selectivity and sensitivity. This is a significant innovation over traditional methods such as [11C]-raclopride that cannot differentiate between D2 and D3 receptors. The use of [11C]-(+)-PHNO will allow for further delineation of the role of D3 receptors. Here, we review recent evidence that the role of the D3 receptor has functional importance and is distinct from the role of the D2 receptor. We then introduce the utility of analyzing [11C]-(+)-PHNO binding by region of interest. This novel methodology can be used in pre-clinical and clinical approaches for the measurement of occupancy of both D3 and D2 receptors. Evidence that [11C]-(+)-PHNO can provide insights into the function of D3 receptors in addiction is also presented.
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影响因子：
2.7
作者：
Ball, Kevin T.;Combs, Tarra A.;Beyer, Denise N.
通讯作者：
Beyer, Denise N.
影响因子：
7.6
作者：
Di Ciano, P;Underwood, RJ;Everitt, BJ
通讯作者：
Everitt, BJ
影响因子：
5.4
作者：
Dodds, Chris M.;O'Neill, Barry;Nathan, Pradeep J.
通讯作者：
Nathan, Pradeep J.
DOI：
10.1017/s1461145712000661
发表时间：
2013-03
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Bergman J;Roof RA;Furman CA;Conroy JL;Mello NK;Sibley DR;Skolnick P
通讯作者：
Skolnick P
影响因子：
7.6
作者：
Andreoli, M;Tessari, M;Heidbreder, CA
通讯作者：
Heidbreder, CA