Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications and perspectives

Publication date: Available online 25 April 2019Source: Pharmacological ResearchAuthor(s): Stefano Comai, Martha Lopez-Canul, Danilo De Gregorio, Ada Posner, Mohamed Ettaoussi, Fabrizia Guarnieri, Gabriella GobbiAbstractMelatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders. However, the selective roles of the MT1 and MT2 receptors need to be clarified. Here, we review the role of the MT1 receptor in neuropsychopharmacology, describe the anatomical localization of MT1 receptors in the brain, discuss the medicinal chemistry, biochemistry and molecular aspects of the receptor, and explore the findings linking MT1 receptors to psychiatric and neurological disorders. MT1 receptors are localized in brain regions which regulate circadian rhythms, sleep, and mood, such as the suprachiasmatic nucleus, cortex, hippocampus, dorsal raphe nucleus and lateral hypothalamus. Their activation modulates intracellular signaling pathways also targeted by psychoactive drugs, including antidepressants and mood stabilizers. MT1 receptor knockout mice display increased anxiety, a depressive-like phenotype, increased propensity to reward and addiction, and reduced Rapid-Eye-Movement sleep. These behavioral dysfunctions are associated with altered serotonergic and ...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research