Melatonin receptor type 2 (MTNR1B)

Melatonin receptor type 2 (MTNR1B) is a high-affinity G protein-coupled receptor primarily activated by melatonin. It is encoded by the *MTNR1B* gene located on human chromosome 11q21–22. This receptor plays a crucial role in synchronizing circadian rhythms and regulating sleep-wake cycles. Beyond its central role in sleep physiology, genetic variations in *MTNR1B* have been strongly linked to an increased risk for type 2 diabetes through their impact on pancreatic beta-cell function and insulin secretion. The MTNR1B/MT2 receptor is also implicated in mood regulation, neuroprotection, learning/memory processes, drug abuse vulnerability, and certain cancers. Several drugs—including melatonin itself as well as synthetic agonists like agomelatine, ramelteon, and tasimelteon—target this molecule therapeutically for conditions such as insomnia or circadian rhythm disturbances[1][3][4]. Selective ligands are under investigation both for their potential efficacy across these indications and their ability to minimize side effects through pathway-selective ("biased") signaling at the MTNR1B/MT2 site[3].

Other names

MT2Melatonin receptor 1BMTNR1B gene product

Agonists bind to and activate the melatonin receptor type 2, leading to downstream signaling via G proteins (primarily Gi/o), resulting in inhibition of cAMP production and modulation of cellular responses related to circadian rhythm regulation, sleep induction, mood stabilization, and metabolic effects[1][3][5].