Melanotan I

In simple words

Melanotan I (afamelanotide) is a peptide drug approved in the US and Europe that makes the skin produce protective dark pigment without sun exposure. It is used for a rare disease involving intolerance to light and is being studied in vitiligo.

What this molecule is

[Nle⁴, D-Phe⁷]-α-MSH — a 13 aa linear tridecapeptide. A synthetic analog of α-MSH with the substitutions Nle⁴ (↑stability) and D-Phe⁷ (↑affinity for MC1R) for metabolic stability.

Why it is studied

FDA-approved (2019) + EMA-approved (2014) — Scenesse® for erythropoietic protoporphyria (EPP). Protective eumelanogenesis without UV exposure. RCTs in N Engl J Med 2015 (74+94 patients). JAMA Dermatol: vitiligo + NB-UVB — repigmentation synergy 48.6% vs 33.3%.

How it works

Highly selective MC1R agonist on melanocytes → ↑adenylate cyclase → ↑cAMP → ↑MITF → ↑tyrosinase → switch from pheomelanin (red, photosensitizing) → eumelanin (brown, photoprotective). A 16 mg implant = a steady level for 60 days.

Doses used in studies

Studies and the approved regimen (Scenesse®) used a 16 mg subcutaneous implant every 60 days — only for EPP and only as prescribed by a physician. It is being studied in vitiligo in combination with NB-UVB.

Combined with in studies

• NB-UVB phototherapy — vitiligo — repigmentation synergy
• Melanostatin/Nonapeptide-1 — NOT combined — antagonism at MC1R
• Melanotan II — DO NOT confuse — a fundamentally different safety profile

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. FDA-approved 2019, EMA-approved 2014. Multiple RCTs in NEJM and JAMA.

Important to know

🔴 Scenesse® is a prescription drug strictly for EPP, used only as prescribed by a physician. It is NOT a cosmetic "tanning" product. Self-treatment is unacceptable.

Studies in PubMed

1. Afamelanotide for Erythropoietic Protoporphyria. (N Engl J Med, 2015)
2. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. (JAMA Dermatol, 2015)
3. Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. (Br J Dermatol, 2015)
4. Mitigating photosensitivity of erythropoietic protoporphyria patients by an agonistic analog of alpha-melanocyte stimulating hormone. (Photochem Photobiol, 2009)
5. Afamelanotide: A Review in Erythropoietic Protoporphyria. (Am J Clin Dermatol, 2016)
6. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. (Obstet Gynecol, 2019)