多巴胺各受体亚型的配体研究进展

Advances in the development of subtype-selective ligands of dopamine receptors

多巴胺在中枢神经系统中是一个非常重要的神经递质。在病理生理学上,大脑多巴胺系统涉及多种神经性疾病,包括:帕金森综合症、精神分裂症、躁狂症、抑郁症、毒品成瘾和饮食混乱等。它的作用主要是通过多巴胺受体的五个亚型(D1～D5)进行调节的。药物化学和神经药理学上对多巴胺D1受体和D2受体的研究已经取得了很大的进展,开发出了一系列具有D1、D2受体选择性的配体及药物;然而开发新型的D3、D4、D5受体选择性配体及药物仍然是一个很大的挑战。本文主要讨论多巴胺受体5种亚型的配体研究进展。

Dysfunctions of the dopaminergic system have been linked with several neurological and psychiat- ric disorders, mainly including Parkinson＇s disease, schizophrenia, depression, attention deficit, hyperactivity disorder and substance abuse. For their distinct differences in gene and peptide composition, dopamine receptors can be divided into five subtypes（D1 -D5 ） that belong to two subfamilies：the Gs-coupled Dl-like receptors （D1, D5 ） and the Gi-coupled or Go-coupled D2-1ike receptors （D2, D3, D4 ）. In recent years, substantial efforts have been directed at the more recently discovered dopamine receptor subtypes D3, D4, and D5, as well as the earlier described D1 and Dzdopamine receptors. This review focuses on the progress of subtype-selective ligands of dopamine receptors gubtype-selective ligands.