Melanin-concentrating hormone 1 receptor (MCHR1)

The **melanin-concentrating hormone 1 receptor** (MCHR1) is a G protein-coupled receptor (GPCR) predominantly expressed in the central nervous system, particularly in brain regions involved in appetite regulation, mood, and arousal[1][4][7]. It is the major receptor for melanin-concentrating hormone (MCH), a cyclic neuropeptide that influences key physiological processes including feeding behavior, energy metabolism, sleep-wake cycles, cognition, and emotion[1][3][6]. MCHR1 acts by coupling primarily to inhibitory G proteins (G_i/o), initiating intracellular signaling that modulates neuronal excitability and neurotransmitter release[3][10]. MCHR1 antagonists have been extensively studied for the potential treatment of obesity—by reducing appetite and body weight—as well as for psychiatric indications such as anxiety and depression, and disorders of sleep[2][6][14]. Despite promising preclinical results, no MCHR1-targeting drug has gained regulatory approval, largely due to efficacy and safety challenges, as well as difficulty achieving brain penetration with candidate compounds[6][8]. Recent structural elucidation has provided insights into ligand binding and receptor activation mechanisms, facilitating rational drug design efforts[1][5].

Other names

MCH1 receptorMCH receptor 1MCH-R1GPR24SLC-1

Antagonists inhibit activation by endogenous melanin-concentrating hormone (MCH), blocking G_i/o-mediated signaling pathways and reducing receptor-induced physiological effects such as increased appetite, weight gain, and anxiety-related behaviors[1][5][8]. Agonists (peptidic and non-peptidic; less developed clinically) mimic MCH activity, promoting feeding behavior or sleep[6].