Melatonin receptor type 1A and Melatonin receptor type 1B (MT1 (for type 1A), MT2 (for type 1B))

Melatonin receptors MT1 (melatonin receptor type 1A) and MT2 (melatonin receptor type 1B) are family A G protein-coupled receptors that mediate the effects of the neurohormone melatonin, primarily in regulating circadian rhythm and sleep patterns[1][2][3][5][9]. MT1 is widely expressed in the brain (notably the suprachiasmatic nucleus), peripheral tissues, and is mostly implicated in the regulation of REM sleep and circadian rhythm[2][7]. MT2 is more selectively expressed (notably in the retina and specific brain regions), where it mediates phase-shifting and regulation of NREM sleep[2][7][10]. Both receptors have similar amino acid sequences and structural features (including a highly occluded orthosteric binding site with unusual membrane-buried ligand entry), but can be pharmacologically distinguished[1][2][5]. Drug development targeting MT1 and MT2 includes approved therapies for insomnia and circadian rhythm disorders (e.g., ramelteon, tasimelteon, agomelatine)[1][3][5][9]. MT2 genetic variants are associated with risk for type 2 diabetes[5]. The two receptors play important physiological roles, impact neuroendocrine function, and are of interest for treating sleep disorders, depression, and metabolic diseases, with additional potential applications in cancer[5][2][9].

Other names

Melatonin receptor MT1MT1 receptorMelatonin receptor type 1AMTNR1AMelatonin receptor MT2MT2 receptorMelatonin receptor type 1BMTNR1B

Agonists bind and activate MT1 or MT2 to mimic or potentiate melatonin's effects, regulating sleep and circadian rhythm[1][3][9][5]. Some agonists may show selectivity or biased signaling at MT1 versus MT2[9]. Antagonists (rare in clinical use) would block melatonin's effects at these receptors.