Update on melatonin receptors: IUPHAR Review 20

Abstract

Melatonin receptors are seven transmembrane-spanning proteins belonging to the GPCR superfamily. In mammals, two melatonin receptor subtypes exist -MT 1 and MT 2 -encoded by the MTNR1A and MTNR1B genes respectively. The current review provides an update on melatonin receptors by the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including radioligands, and give an update on the latest phenotyping results of melatonin receptor knockout mice. The current status and perspectives of the structure of melatonin receptor will be summarized. The physiological importance of melatonin receptor dimers and biologically important and type 2 diabetes-associated genetic variants of melatonin receptors will be discussed. The role of melatonin receptors in physiology and disease will be further exemplified by their functions in the immune system and the CNS. Finally, antioxidant and free radical scavenger properties of melatonin and its relation to melatonin receptors will be critically addressed.

Pathophysiology of Depression: Molecular Regulation of Melatonin Homeostasis – Current Status

“…This effect is mediated by two types of melatonin receptors, well characterized in mammals by Dubocovich et al [29]. Thanks to these studies, the main types of receptors were finally distinguished and characterized: MT 1 and MT 2 (MEL1A and MEL1B or MTNR1A and MTNR1B) (review [30-32]). Both receptors are G-coupled 7-transmembrane receptors [33].…”

“…Additionally, receptor gene variants may cause receptor expression and function as well as increase the risk of disease and affect drug efficacy. Jockers et al [32] reported several nonsynonymous variants in both types of receptors; this list will be extended along with subsequent tests.…”

“…Clinical and preclinical results are very promising, and indicate that selective ligands targeting melatonin receptors may improve the efficacy of pharmacotherapy [32, 43]. …”

“…Detailed information can also be found at Drug Bank [94]. Research into the role of various selective ligands of melatonin MT 1 and MT 2 receptors in the modulation of circadian rhythms in animal models is ongoing, with the aim of ultimately discovering new drugs with different effects on MT 1 and MT 2 receptors [32]. …”

Twenty Years After: Another Case Report of Melatonin Effects on REM Sleep Behavior Disorder, Using Serial Dopamine Transporter Imaging

“…Neuroprotective effects of melatonin have been reported in the literature at the molecular, cellular, and tissue level in vitro and in animal models (reviewed by Mack et al [14]), to be achieved either by direct cellular scavenger mechanisms [15] or by melatonin receptor-mediated pathways [16]. At present, we have no indication or suggestion which of these or other mechanisms could be responsible for the remarkable improvement of the patient’s condition with melatonin treatment.…”