Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology

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J Psychiatry Neurosci 2013; 39(1): 6-21

Stefano Comai, PhD; Gabriella Gobbi, MD, PhD

Ira, Zanoni, Ruggeri, Tosato — Section of Psychiatry, University of Verona, Verona, Italy; Dazzan — Institute of Psychiatry, Department of Psychosis Studies, King’s College, London, United Kingdom

Abstract

Background: Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT1 (MEL1a) and MT2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT1 and MT2 receptors. Here we have reviewed current knowledge about the implications of MT2 receptors in brain functions.

Methods: We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT2 receptor.

Results: These studies demonstrate that MT2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT2 receptor agonists show hypnotic and anxiolytic properties. Limitations

Limitations: Studies examining the role of MT2 receptors in psychopharmacology are still limited.

Conclusion: T he development of novel selective MT2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, MT2 receptors have great potential for pioneer drug discovery in the treatment of mental diseases for which limited therapeutic targets are currently available.


Submitted Jan. 14, 2013; Revised Mar. 31, 2013; Accepted Apr. 12, 2013.

Acknowledgments: This work was supported by grants from the Fonds de la Recherche en Santé du Québec (FRSQ), the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for Innovation (CFI), MSBi Valorisation, the McGill University Health Center (MUHC).

Competing interests: None declared by S. Comai. G. Gobbi has received payment for lectures from Lilly and AstraZeneca. She is also the inventor of the patent Pub. No. WO/2007/079593, International Application No. PCT /CA2007 /000055).

Contributors: Both authors contributed equally to this work.

DOI: 10.1503/jpn.130009

Correspondence to: G. Gobbi, Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Ave. W, room 220, Montréal QC H3A 1A1; gabriella.gobbi@mcgill.ca