title: MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.
abstract: Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Jiabei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Clough
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hutchinson
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Ekue B
authors.initials: EB
authors.lastname: Adamah-Biassi
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Marina
authors.initials: M
authors.lastname: Popovska-Gorevski
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214; email: jl284@buffalo.edu , shannonc@buffalo.edu , ah64@buffalo.edu , eba@buffalo.edu , mgorevsk@buffalo.edu , mdubo@buffalo.edu.
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Dubocovich
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000378:metabolism
chemical_list: D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: cancer; circadian rhythm disorders; depression; drugs of abuse; neuroprotection; sleep disorders