Serotonin 5-HT7 receptor agents: structure-activity relationships and potential therapeutic applications in central nervous system disorders

摘要

Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous\udsystem, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human\udfunctions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of\udneuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to\udbe classified as specific protein molecules encoded by specific genes. The 5-HT7 receptor is the most recently\udclassified member of the serotonin receptor family. Since its identification, it has been the subject of intense\udresearch efforts driven by its presence in functionally relevant regions of the brain. The availability of some\udselective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT7 receptor,\udhas allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data\udon localization and pharmacological properties of the 5-HT7 receptor, and summarizes the results of\udstructure-activity relationship studies aimed at the discovery of selective 5-HT7 receptor ligands. Additionally,\udan overview of the potential therapeutic applications of 5-HT7 receptor agonists and antagonists in central\udnervous system disorders is presented.