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

Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are high-affinity G protein-coupled receptors that bind the pineal hormone melatonin[2][5]. These receptors mediate melatonin’s physiological roles in synchronizing circadian rhythms, promoting sleep, and modulating mood, metabolism, and other neuroendocrine functions[1][3][7][9]. MT1 and MT2 are encoded by the genes MTNR1A and MTNR1B, respectively, and are expressed in brain regions such as the suprachiasmatic nucleus (the central circadian pacemaker), retina, and various peripheral tissues[2][5][6]. While both receptors regulate sleep and circadian phase, MT1 is mainly involved in REM sleep and suppressing neuronal activity in the SCN, whereas MT2 regulates phase-shifting and NREM sleep[7]. Clinically, both are validated drug targets for the treatment of insomnia and certain circadian rhythm disorders. Structural studies have facilitated the rational design of selective agonists and antagonists, though challenges remain in developing subtype-selective drugs. More recently, genetic variation in MT2 (MTNR1B) has been linked to type 2 diabetes susceptibility, suggesting a broader physiological and pathological role for these receptors[3].

Other names

MT1 (Mel1A, MTNR1A)MT2 (Mel1B, MTNR1B)Melatonin receptor 1A, Melatonin receptor 1BMelatonin G protein-coupled receptorMelatonin GPCR

Agonism at MT1/MT2 (promotes sleep, adjusts circadian phase); Inhibition of adenylate cyclase via Gi/o protein activation; Subtype-selective agonism (MT1: REM sleep regulation/MT2: NREM and phase-shifting)