Werkman T R, Glennon J C, Wadman W J, McCreary A C
Center for NeuroScience, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):3-23. doi: 10.2174/187152706784111614.
The classification of dopamine receptors proposed more than two decades ago remains valid today. Based on biochemical and pharmaceutical properties two main classes of dopamine receptors can be distinguished: D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), and D(4)) dopamine receptors. Dopamine receptors belong to the class of G protein-coupled receptors and signal to a wide range of membrane bound and intracellular effectors such as ion channels, secondary messenger systems and enzymes. Although the pharmacological properties of ligands for D(1)-like and D(2)-like dopamine receptors are quite different, the number of selective ligands for each of the five receptors subtypes is rather small. Many drugs used to treat neurological and neuropsychiatric disorders like Parkinson's disease, restless leg syndrome and schizophrenia have affinities for dopamine receptors. Such medications are not without limitations so the development of novel (selective or aselective) dopamine receptor ligands is of the utmost importance for improved therapeutic approaches for these diseases. In that respect it is also important to understand how dopamine receptor ligands affect receptor signalling processes such as desensitization, receptor heterodimerization and agonist-receptor trafficking, issues which will be discussed in the present review. Furthermore, attention is paid to interactions of dopamine receptors with serotonin receptors since many drugs used to treat above mentioned disorders of the brain also possess affinities for serotonin receptors. Because of the enormity of this area we have tried to focus more specifically on interactions within the prefrontal cortex where it appears that the serotonergic modulation of dopaminergic function might be very relevant to schizophrenia.
二十多年前提出的多巴胺受体分类如今仍然有效。根据生化和药理学特性，可以区分出两类主要的多巴胺受体：D(1)样（D(1)、D(5)）和D(2)样（D(2)、D(3)和D(4)）多巴胺受体。多巴胺受体属于G蛋白偶联受体类别，可向多种膜结合和细胞内效应器发出信号，如离子通道、第二信使系统和酶。尽管D(1)样和D(2)样多巴胺受体配体的药理学特性有很大差异，但五种受体亚型各自的选择性配体数量相当少。许多用于治疗帕金森病、不宁腿综合征和精神分裂症等神经和神经精神疾病的药物对多巴胺受体有亲和力。这类药物并非没有局限性，因此开发新型（选择性或非选择性）多巴胺受体配体对于改善这些疾病的治疗方法至关重要。在这方面，了解多巴胺受体配体如何影响受体信号传导过程，如脱敏、受体异二聚化和激动剂-受体转运等问题也很重要，这些问题将在本综述中讨论。此外，还关注多巴胺受体与5-羟色胺受体的相互作用，因为许多用于治疗上述脑部疾病的药物对5-羟色胺受体也有亲和力。由于这一领域范围广泛，我们试图更具体地关注前额叶皮质内的相互作用，在那里，多巴胺能功能的5-羟色胺能调节似乎与精神分裂症密切相关。
