Melanocortin receptors

Melanocortin receptors are a family of five receptors activated by hormones derived from pro-opiomelanocortin, chiefly alpha-melanocyte-stimulating hormone. Each receptor governs something different. MC1R on skin cells drives pigmentation. MC4R in the brain regulates appetite, energy balance and sexual arousal. MC3R and MC5R have roles in inflammation and exocrine function. Because a single natural hormone hits several of them, synthetic analogues are designed for selectivity.

Three compounds profiled here act through this system. Melanotan II is a non-selective analogue whose tanning effect comes from MC1R and whose nausea and erectile effects come from MC4R; the latter observation led directly to PT-141, bremelanotide, which was developed for MC4R and is approved in the United States as Vyleesi for low sexual desire in premenopausal women. KPV is the three-residue C-terminal fragment of α-MSH, studied for anti-inflammatory effects that appear to be independent of the classical receptors.

The pigmentation link is also the source of melanotan II's best-documented safety concern, the darkening of existing moles, which its profile covers under "Side effects and safety signals". The article on melanocyte and skin peptides covers the family.