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靶向血清素受体的多靶点导向配体：药物化学综述。

Multitarget-Directed Ligands Hitting Serotonin Receptors: A Medicinal Chemistry Survey.

作者信息

Ghafir El Idrissi Imane, Santo Angela, Lacivita Enza, Leopoldo Marcello

机构信息

Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via Orabona, 4, 70125 Bari, Italy.

出版信息

Pharmaceuticals (Basel). 2024 Sep 19;17(9):1238. doi: 10.3390/ph17091238.

DOI:10.3390/ph17091238
PMID:39338400
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12068022/
Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a ubiquitous neurotransmitter in the human body. In the central nervous system, 5-HT affects sleep, pain, mood, appetite, and attention, while in the peripheral nervous system, 5-HT modulates peristalsis, mucus production, and blood vessel dilation. Fourteen membrane receptors mediate 5-HT activity. In agreement with the crucial roles played by 5-HT, many drugs target 5-HT receptors (5-HTRs). Therefore, it is unsurprising that many efforts have been devoted to discovering multitarget-directed ligands (MTDLs) capable of engaging one or more 5-HTRs plus another target phenotypically linked to a particular disease. In this review, we will describe medicinal chemistry efforts in designing MTDLs encompassing activity for one or more 5-HTRs, starting with atypical antipsychotics and moving to dual 5-HT1AR/serotonin transporter ligands, 5-HT6R antagonists/acetyl cholinesterases inhibitors, and 5-HT4R agonists/acetyl cholinesterases inhibitors. We will also provide an outlook on the most recent efforts made in the field.

摘要

血清素（5-羟色胺，5-HT）是人体中一种普遍存在的神经递质。在中枢神经系统中，5-HT影响睡眠、疼痛、情绪、食欲和注意力，而在周围神经系统中，5-HT调节蠕动、黏液分泌和血管舒张。14种膜受体介导5-HT的活性。鉴于5-HT发挥的关键作用，许多药物都以5-HT受体（5-HTRs）为靶点。因此，人们致力于发现能够作用于一种或多种5-HTRs以及另一个与特定疾病表型相关靶点的多靶点导向配体（MTDLs），这也就不足为奇了。在这篇综述中，我们将描述药物化学在设计包含一种或多种5-HTRs活性的MTDLs方面所做的努力，从非典型抗精神病药物开始，进而介绍5-HT1AR/血清素转运体双重配体、5-HT6R拮抗剂/乙酰胆碱酯酶抑制剂以及5-HT4R激动剂/乙酰胆碱酯酶抑制剂。我们还将对该领域最近的研究进展进行展望。

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