Development of a Tritiated Agonist Radioligand for the D2 Receptor

描述(申请人提供)：该项目的目标是开发一种新的激动剂放射性配基，用于评估处于高状态的D2受体的比例。D2高受体被认为是内源性多巴胺结合的D2受体的功能形式。激动剂放射配体应该比拮抗剂放射配体对内源性DA水平更敏感，因为与拮抗剂不同，激动剂放射配体优先与受体结合。 它的高亲和力状态。因此，激动剂放射性配基有可能阐明受体亚型活性作为疾病的函数以及DA系统整体活性的更详细的信息。大多数可用的放射性配基是基于D2拮抗剂，因此不专门针对D2高状态。在商业上可用的激动剂配体中，没有一种对D2比D3具有高的选择性。相比之下，氟阿朴吗啡是该项目的重点，是D2受体激动剂，特异性和选择性地靶向D2High受体。因此，本项目的目标是开发~3H标记的氟阿朴吗啡作为体外结合研究的放射性配体，并用于放射自显影，以帮助评估和研究D2高受体功能在脑中的作用。

DESCRIPTION (provided by applicant): The goal of this project is to develop a novel agonist radioligand for evaluating the proportion of D2 receptors in the high state. The D2high receptor is thought to be the functional form of the D2 receptor to which endogenous dopamine binds. An agonist radioligand should be more sensitive to endogenous DA levels than antagonist radioligands since, unlike antagonists, agonist radioligands bind preferentially to the receptor in its high affinity state. Thus, agonist radioligands have the potential to elucidate more detailed information on receptor subtype activity as a function of disease as well as DA system activity as a whole. The majority of available radioligands are based on D2 antagonists and, as such, do not specifically target the D2high state. Among the commercially available agonist ligands, none possess high selectivity for D2 over D3. In contrast, fluoroaporphines, which are the focus of this project, are D2 receptor agonists that specifically and selectively target D2high receptors. The objective of this project is, therefore, to develop 3H-labeled fluoroaporphines as radioligands for in vitro binding studies and for autoradiography to aid in the evaluation and study of the role of the D2high receptor function in the brain.