MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective

• Published in: Annual review of pharmacology and toxicology Vol. 56; pp. 361 - 383
• Main Authors: Liu, Jiabei, Clough, Shannon J, Hutchinson, Anthony J, Adamah-Biassi, Ekue B, Popovska-Gorevski, Marina, Dubocovich, Margarita L
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 06-01-2016
• Subjects: Animals; cancer; Circadian Rhythm - physiology; circadian rhythm disorders; depression; drugs of abuse; Humans; Ligands; Melatonin - metabolism; Neoplasms - drug therapy; Neoplasms - metabolism; neuroprotection; Receptor, Melatonin, MT1 - metabolism; Receptor, Melatonin, MT2 - metabolism; sleep disorders; Sleep Wake Disorders - drug therapy; Sleep Wake Disorders - metabolism; drugs of abuse; sleep disorders; cancer; depression; circadian rhythm disorders; neuroprotection
• ISSN: 0362-1642; 1545-4304
• DOI: 10.1146/annurev-pharmtox-010814-124742

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 MT
1
and MT
2
, 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 MT
1
and MT
2
receptor activation. Discovery of selective ligands targeting the MT
1
or the MT
2
melatonin receptors may promote the development of novel and more efficacious therapeutic agents.