Melanotan I (Afamelanotide)

Mechanism

Afamelanotide is a 13-amino-acid peptide analogue of α-MSH with potent agonist activity at the melanocortin-1 receptor (MC1R). Activation of MC1R on melanocytes stimulates eumelanin (dark pigment) production via the cAMP signalling pathway, increasing skin pigmentation and providing UV photoprotection. Unlike Melanotan II, afamelanotide has minimal activity at MC3R and MC4R, reducing the sexual and appetite effects associated with Melanotan II.

Evidence base

Evidence Grading: Moderate

Human clinical data: Two Phase 3 RCTs and long-term safety studies support efficacy for EPP. Approved by EMA (2019) and FDA (2019). Smaller studies for vitiligo, PLE, and solar urticaria.

Limitations: Evidence for indications beyond EPP is limited. Long-term safety data (>5 years) is still accumulating. Cosmetic use is not approved and lacks safety data in healthy populations.

Key distinction: Afamelanotide (Melanotan I) has a more selective receptor profile and better safety profile than Melanotan II, which is not approved anywhere.

Protocols

Approved regimen: 16 mg subcutaneous implant every 2 months for EPP. Earlier research used 0.16–0.25 mg/kg SC injections. Research discussion contexts reference 0.5–1.0 mg SC, but these do not reflect the approved formulation.

UK legal status

Afamelanotide (Scenesse) is a POM in the UK, EMA-approved for erythropoietic protoporphyria. Available through specialist centres. Non-prescription sale for cosmetic or research purposes violates UK medicines regulations. The MHRA's 2026 guidance on research peptide labelling applies to any research-grade material.

Vendor notes

Scenesse implants are available only through specialist medical channels for EPP. Research-grade afamelanotide may be available from some UK research chemical suppliers. Verify COAs. See the vendor vetting guide for evaluation criteria.