Melatonin receptor type 1 and Melatonin receptor type 2 (MT1 and MT2)

Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are high-affinity G protein-coupled receptors that mediate the effects of melatonin, a neurohormone critical in the regulation of circadian rhythm and sleep. MT1 is broadly expressed in multiple tissues including the brain, liver, kidney, and reproductive organs, while MT2 expression is relatively restricted to the central nervous system and retina but also appears in peripheral tissues such as bone and cardiovascular tissue[4][5]. These receptors show 55–70% sequence homology and share structural features with other family A GPCRs, yet possess distinct ligand and protein interaction motifs. MT1 primarily suppresses neuronal firing and is important for rapid eye movement (REM) sleep; MT2 is crucial for phase-shifting the circadian clock, non-REM sleep, vasodilation, and is implicated in mood regulation and protection from neuronal damage after ischemic injury[4][5][6]. Drugs targeting these receptors are important therapeutics for insomnia, depression, circadian rhythm disorders, and emerging applications in metabolic and neurodegenerative diseases. Despite their overlapping roles, molecular and physiological data reveal distinctive and sometimes synergistic or opposing downstream responses, leading to an ongoing need for selective ligands with improved safety and efficacy profiles[1][2][3][6][8].

Other names

MT1 (Melatonin receptor type 1)MT2 (Melatonin receptor type 2)Melatonin receptorsMelatonin G protein-coupled receptor 1Melatonin G protein-coupled receptor 2

Agonism: Activation of MT1 and/or MT2 promotes sleep, circadian entrainment, neuroprotection, vasodilation, and mood regulation[1][2][3][4][6][8]. Antagonism: Inhibition of receptor signaling, mainly used experimentally for dissecting receptor roles.