Myslivecek Jaromir
Institute of Physiology, 1st Faculty of Medicine, Charles University, Albertov 5, 128 00 Prague, Czech Republic.
Life (Basel). 2022 Apr 19;12(5):606. doi: 10.3390/life12050606.
The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation by the D-like receptor family. Some dopamine drugs (both agonists and antagonists) bind in addition to DRs also to α-ARs and 5-HT receptors. Unfortunately, these compounds are often considered subtype(s) specific. Thus, it is important to consider the presence of these receptor subtypes in specific CNS areas as the function virtually elicited by one receptor type could be an effect of other-or the co-effect of multiple receptors. However, there are enough molecules with adequate specificity. In this review, we want to give an overview of the most common off-targets for established dopamine receptor ligands. To give an overall picture, we included a discussion on subtype selectivity. Molecules used as antipsychotic drugs are reviewed too. Therefore, we will summarize reported affinities and give an outline of molecules sufficiently specific for one or more subtypes (i.e., for subfamily), the presence of DR, α-ARs, and 5-HT receptors in CNS areas, which could help avoid ambiguous results.
多巴胺能系统是中枢神经系统（CNS）中最重要的神经递质系统之一。它主要通过激活靶细胞上的D样受体家族来发挥作用。此外，通过D样受体家族的突触前调节实现信号的微调。一些多巴胺药物（激动剂和拮抗剂）除了与多巴胺受体（DRs）结合外，还与α-肾上腺素能受体（α-ARs）和5-羟色胺受体结合。不幸的是，这些化合物通常被认为具有亚型特异性。因此，考虑特定中枢神经系统区域中这些受体亚型的存在很重要，因为一种受体类型实际引发的功能可能是其他受体的作用——或者是多种受体的共同作用。然而，有足够多具有足够特异性的分子。在这篇综述中，我们想概述已确立的多巴胺受体配体最常见的脱靶情况。为了给出一个总体情况，我们纳入了关于亚型选择性的讨论。还对用作抗精神病药物的分子进行了综述。因此，我们将总结报道的亲和力，并概述对一种或多种亚型（即对亚家族）具有足够特异性的分子、中枢神经系统区域中多巴胺受体、α-肾上腺素能受体和5-羟色胺受体的存在情况，这有助于避免产生模糊的结果。
