Melanotan I

Overview

Melanotan I (Afamelanotide) is a synthetic analog of alpha-MSH that selectively activates MC1R. FDA-approved as Scenesse for erythropoietic protoporphyria (EPP), it is distinct from Melanotan II and is studied for melanogenesis and photoprotection.

Mechanism of Action

Melanotan I selectively agonizes MC1R on melanocytes, activating adenylyl cyclase and the MITF-TYR-TYRP1 melanogenesis cascade, increasing eumelanin production without UV exposure. Two key modifications (Nle4 and D-Phe7) confer enhanced binding affinity and protease resistance. Unlike Melanotan II, it has minimal MC3R/MC4R/MC5R activity.

Research Summary

FDA-approved as Scenesse (Clinuvel, 2019) for EPP based on Phase III trials CUV039 and CUV040 showing increased time to first phototoxic reaction (Langendonk et al., NEJM, 2015). Phase II vitiligo trials showed increased repigmentation with narrow-band UVB (Lim et al., BJD, 2015).

Dosing Information

Reported Side Effects

• Nausea (most frequently reported)
• Facial flushing
• Darkening of pre-existing moles and nevi
• Headache
• Implant site reactions

Research References

• Afamelanotide for Erythropoietic Protoporphyria (2015)
• Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial (2015)