Α-Melanocyte-stimulating hormone

α-MSH is a non-selective full agonist of the melanocortin receptors MC₁ (K_i = 0.230 nM), MC₃ (K_i = 31.5 nM), MC₄ (K_i = 900 nM), and MC₅ (K_i = 7160 nM), but not MC₂ (which is exclusive for adrenocorticotropic hormone (ACTH)). Activation of the MC₁ receptor is responsible for its effect on pigmentation, whereas its regulation of appetite, metabolism, and sexual behavior is mediated through both the MC₃ and MC₄ receptors.

It is generated as a proteolyic cleavage product from ACTH (1-13), which is in turn a cleavage product of proopiomelanocortin (POMC).

A few synthetic analogues of α-MSH have been investigated as medicinal drugs due to their photoprotective effects against ultraviolet (UV) radiation from the sun. They include afamelanotide (melanotan) and melanotan II, the former of which has been approved as a treatment to reduce photosensitivity in erythropoietic protoporphyria in the United States. Bremelanotide, another analogue of α-MSH, is available in the United States not as a photoprotective agent, but for the treatment of hypoactive sexual desire disorder in premenopausal women. All of these drugs have significantly greater potencies than α-MSH, along with improved pharmacokinetics and distinctive selectivity profiles.