The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT3 and 5-HT4 receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT3R and 5-HT4R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT3R and 5-HT4R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.
Keywords: Serotonin, serotonin receptor subtypes, 5-HT3R, 5-HT4R, 5-HT3R ligands, 5-HT4R ligands, ligand-gated ion channels, G protein-coupled receptors
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