Melanotan I

Melanotan I (afamelanotide) is a linear 13-amino acid analog of α-MSH developed at the University of Arizona with enhanced MC1R selectivity and metabolic stability compared to the native hormone. The key modification is substitution of methionine-4 with norleucine (Nle) and phenylalanine-7 with D-phenylalanine (D-Phe), providing resistance to enzymatic degradation. Approved by the EMA as Scenesse (2014) for prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), afamelanotide is the only approved melanocortin-based tanning agent. It stimulates eumelanin production without UV exposure, providing photoprotection for patients with extreme UV sensitivity. Unlike Melanotan II, afamelanotide is relatively selective for MC1R with minimal sexual or appetite effects.

Afamelanotide selectively activates MC1R on melanocytes, stimulating eumelanin synthesis through the cAMP/PKA/CREB/MITF/tyrosinase cascade. Eumelanin absorbs UV radiation and scavenges free radicals, providing photoprotection. The D-Phe substitution prevents DPP-4 degradation, extending half-life to ~30 minutes (vs minutes for native α-MSH).

Erythropoietic Protoporphyria (Approved) Scenesse implant reduces phototoxicity episodes and allows increased sun exposure in EPP patients. Photoprotection Research Studied for prevention of UV-induced skin damage and potentially skin cancer prevention through melanin-based photoprotection. Vitiligo Research combining afamelanotide with narrow-band UVB therapy shows enhanced repigmentation.

MC1R/Gαs/cAMP/PKA/CREB/MITF for melanogenesis. Tyrosinase/TRP-1/TRP-2 for eumelanin synthesis. p53-mediated DNA repair enhancement in melanocytes.

Nausea (most common), skin darkening (expected/desired), headache, nasopharyngitis. Implant site reactions. Mole darkening — dermatological monitoring recommended.

Scenesse is a subcutaneous implant (16 mg) providing sustained release over ~60 days. Research-grade powder stores at -20°C. More stable than native α-MSH due to Nle/D-Phe substitutions.

EMA-approved as Scenesse (2014) for EPP. Not FDA-approved (though FDA has granted breakthrough therapy designation). Prescription medication in Europe/Australia.