Dipartimento Farmaco-Chimico, Università degli Studi di Bari "A. Moro", via Orabona, 4, 70125 Bari, Italy.
Pharmacol Ther. 2011 Feb;129(2):120-48. doi: 10.1016/j.pharmthera.2010.08.013. Epub 2010 Oct 20.
Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous system, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human functions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of neuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The 5-HT(7) receptor is the most recently classified member of the serotonin receptor family. Since its identification, it has been the subject of intense research efforts driven by its presence in functionally relevant regions of the brain. The availability of some selective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT(7) receptor, has allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data on localization and pharmacological properties of the 5-HT(7) receptor, and summarizes the results of structure-activity relationship studies aimed at the discovery of selective 5-HT(7) receptor ligands. Additionally, an overview of the potential therapeutic applications of 5-HT(7) receptor agonists and antagonists in central nervous system disorders is presented.
自 20 世纪 40 年代在血清、哺乳动物肠黏膜和中枢神经系统中发现以来，血清素（5-HT）已被证明参与了几乎所有的认知和行为人类功能，其神经化学的改变与多种神经精神疾病的病因有关。5-HT 受体亚型的克隆对于将它们分类为特定基因编码的特定蛋白质分子非常重要。5-HT（7）受体是最近分类的血清素受体家族成员。自其被鉴定以来，由于其存在于大脑的功能相关区域，它一直是研究的热点。一些选择性拮抗剂和激动剂的出现，以及缺乏 5-HT（7）受体的基因修饰小鼠，使人们能够更好地了解该受体的病理生理作用。本文综述了 5-HT（7）受体的定位和药理学特性的数据，并总结了旨在发现选择性 5-HT（7）受体配体的构效关系研究的结果。此外，还介绍了 5-HT（7）受体激动剂和拮抗剂在中枢神经系统疾病中的潜在治疗应用。
