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Recent Progress in the Development of Agonists and Antagonists for Melatonin Receptors

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The various physiological actions of the neurohormone melatonin are mediated mainly by two G-protein-coupled MT1 and MT2 receptors. The melatoninergic drugs on the market, ramelteon and agomelatine, as well as the most advanced drug candidates under clinical evaluation, tasimelteon and PD-6735, are high-affinity nonselective MT1 and MT2 agonists. However, exploring the exact physiological role of the MT1 and MT2 melatonin receptors requires subtype selective MT1 and MT2 ligands. This review covers novel melatoninergic agonists and antagonists published since 2010, focusing on high-affinity and subtype selective agents. Additionally, compounds not mentioned in the previous review articles and ligands selective for the MT3 binding site are included.
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Keywords: MT1 receptors; MT2 receptors; MT3 binding site; Melatonin; insomnia; melatonin receptor agonists; melatonin receptor antagonists; melatonin receptor partial agonists; selective ligands; sleep disorders

Document Type: Research Article

Publication date: July 1, 2012

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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