Melanotan I

Melanotan I (Afamelanotide) is a synthetic 13-amino-acid linear peptide analog of alpha-melanocyte-stimulating hormone (alpha-MSH), developed at the University of Arizona. It differs from native alpha-MSH by two amino acid substitutions: norleucine replacing methionine at position 4 and D-phenylalanine replacing L-phenylalanine at position 7. These modifications confer greater receptor affinity, increased potency, and enhanced metabolic stability compared to the natural hormone.

Melanotan I primarily acts through the MC1R (melanocortin-1 receptor) on melanocytes, stimulating the production of eumelanin, the photoprotective dark pigment in skin. Unlike Melanotan II, it has higher selectivity for MC1R and significantly less activity at MC3R, MC4R, and MC5R, meaning it produces skin tanning without the sexual side effects, appetite suppression, or other systemic effects associated with non-selective melanocortin agonism.

Afamelanotide is FDA-approved and EMA-approved under the brand name Scenesse for the treatment of erythropoietic protoporphyria (EPP), a rare genetic condition causing severe light sensitivity. Clinical trials demonstrated that afamelanotide significantly increased pain-free time in sunlight for EPP patients. Beyond EPP, research has explored its potential for vitiligo (promoting repigmentation), polymorphous light eruption, solar urticaria, and as a general photoprotective agent to reduce UV-induced DNA damage and skin cancer risk. Its selective mechanism makes it a safer tanning peptide compared to Melanotan II.