Melanotan II vs Afamelanotide

Melanotan II is a cyclic analogue of alpha-MSH developed as a more potent melanotropic peptide ¹. Its published human evidence is thin: a 1996 single-blind pilot in 3 male volunteers reported increased pigmentation of the face, upper body and buttock, intermittent erections, and side effects including somnolence, fatigue and mild nausea ¹. Later double-blind studies of the related analogue in erectile dysfunction were reported by the same research line ².

Most of the recent literature concerns harm from unregulated use. Case reports describe melanoma arising in a 20-year-old after a self-injection course ⁴, atypical melanocytic naevi ¹⁰, and priapism requiring cavernosal aspiration and phenylephrine ⁵. A 2017 review of alpha-MSH analogue use describes melanocytic changes, new dysplastic naevi and four melanoma case reports, and notes that preparation and content of illicit products are uncertain ³. The FDA lists Melanotan II among withdrawn category 2 compounding nominations, citing melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism ¹¹.

Afamelanotide is a 13-amino-acid alpha-MSH analogue that binds predominantly to the melanocortin-1 receptor and increases eumelanin production in skin without UV exposure ⁶. It is given as a controlled-release subcutaneous implant, with an apparent half-life of about 15 hours measured in 12 healthy adults ⁶.

Two multicentre randomised, double-blind, placebo-controlled trials in erythropoietic protoporphyria (74 patients in the EU, 94 in the US) found longer pain-free sun exposure with afamelanotide than placebo, and fewer phototoxic reactions in the EU trial ⁹. It was authorised in the EU in December 2014 under exceptional circumstances and approved in the US on 8 October 2019 ^7,8,9. Across three trials with 125 recipients, the label reports implant site reactions in 21% versus 10% with vehicle and nausea in 19% versus 14%, with hypersensitivity including anaphylaxis reported after approval ⁶.