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α-MSH analog (MC1R/MC4R agonist)

Melanotan I

Also known as: MT-1, MT-I, Afamelanotide, Scenesse, [Nle4, D-Phe7]-α-MSH

Tier 1 — Human RCTReviewed 2026-05-04

FDA-approved as Scenesse / afamelanotide for erythropoietic protoporphyria (Tier 1 for that single rare indication). Distinct from the more popular community 'tanning peptide' MT-2 — note this is the regulated one.

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Overview

Melanotan I (MT-1) is a synthetic 13-amino-acid analog of α-MSH. Unlike its close relative Melanotan II — a heavily community-used 'tanning peptide' with a much messier safety profile — MT-1 was developed as a pharmaceutical and is now FDA-approved as Scenesse (afamelanotide), a slow-release subcutaneous implant for erythropoietic protoporphyria (EPP), an ultra-rare genetic light-sensitivity disorder. EU approval came in 2014 and FDA approval in 2019. Outside that single approved indication, MT-1 is also used off-label for vitiligo (some published trials) and as a tanning agent (community use), where evidence drops to Tier 3. Be careful not to conflate MT-1 with MT-2 — the regulatory and safety stories are very different.

Mechanism

Selective agonist at melanocortin receptors, primarily MC1R (drives melanogenesis in melanocytes — the photoprotective mechanism in EPP and the cosmetic mechanism for tanning) and MC4R (modulates appetite and sexual function, less prominent than at MC3R/MC4R for MT-2). Stimulates eumelanin synthesis, providing endogenous photoprotection against UV-driven and visible-light-driven phototoxic skin reactions.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Erythropoietic protoporphyria (EPP) — phototoxicity prevention

Tier 1high confidence

FDA-approved as Scenesse in 2019 (EU 2014). Phase 3 program (Langendonk et al., NEJM 2015) demonstrated significantly reduced phototoxic reactions and increased pain-free sun exposure time. Tier 1 specifically for THIS rare indication with the implant formulation.

Vitiligo (adjunct, with phototherapy)

Tier 2high confidence

Multiple controlled trials of afamelanotide combined with NB-UVB phototherapy show faster and more extensive repigmentation in non-segmental vitiligo than NB-UVB alone (Lim et al., JAMA Dermatology 2015). Tier 2 because evidence is replicated but not yet at the regulatory-approval scale.

Cosmetic tanning

Tier 3high confidence

MT-1 does drive melanogenesis. Cosmetic tanning is not a regulator-approved indication and the safety profile is studied in EPP and vitiligo populations under medical supervision, not in chronic recreational use. The risk/benefit calculus for healthy adults seeking cosmetic tan does not match the regulatory data.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Other photoprotection (e.g., polymorphous light eruption, solar urticaria)

Tier 3medium confidence

Small case series and uncontrolled reports support photoprotective benefit in these less-common photodermatoses. Limited controlled-trial replication.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

16,00016,000 mcgevery 2 months · subcutaneous controlled-release implant (Scenesse, EPP)

Scenesse implant: 16 mg afamelanotide per implant, inserted subcutaneously every 2 months during high-light-exposure periods. Note unit math: 16 mg = 16,000 mcg per implant.

2001,000 mcgevery 1–2 days during loading; 1–2× weekly maintenance · subcutaneous (off-label / community)

Off-label SubQ MT-1 dosing varies widely in the community. There is no validated injectable-MT-1 protocol outside the implant. Less popular for tanning than MT-2.

Contraindications

  • History of melanoma or non-melanoma skin cancer (theoretical concern from sustained MC1R activation; melanoma surveillance is part of approved-product labeling)
  • Hypersensitivity to afamelanotide or formulation excipients
  • Pregnancy and breastfeeding (limited safety data outside indication populations)
  • Significant pre-existing pigmented lesions requiring surveillance

Reported side effects

  • Implant-site reactions (pain, erythema, hyperpigmentation at insertion site)
  • Diffuse skin darkening (the on-target effect; expected)
  • New or darkened nevi (mole surveillance is part of routine post-implant care)
  • Headache
  • Nausea (less prominent than with MT-2)
  • Fatigue
  • Decreased appetite (modest; MC4R-mediated)

Reconstitution & storage

Scenesse implant is supplied pre-formulated and inserted by a trained healthcare professional — no patient reconstitution. Off-label/research lyophilized MT-1 powder reconstituted with bacteriostatic water; concentrations vary by vendor — verify per batch.

Storage. Scenesse implant: refrigerate per label until use. Lyophilized off-label powder: refrigerate; reconstituted: refrigerate 2–8 °C, use within 30 days.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

DRAFT — pending Wayne's review. MT-1 (afamelanotide / Scenesse) is the rare melanocortin analog that actually made it through FDA — for a single rare indication. The tier framework holds: Tier 1 for EPP only, Tier 2 for vitiligo + phototherapy, Tier 3 for cosmetic tanning. The most important editorial point is the disambiguation from MT-2 — they are not the same molecule and the regulatory and safety stories are very different. Cross-reference MT-2 entry explicitly.

Citations

  1. [1]
    Afamelanotide for Erythropoietic Protoporphyria
    Langendonk JG, Balwani M, Anderson KE, et al. · New England Journal of Medicine · 2015 · PMID 26132939
    Tier 1 anchor — the Phase 3 trial supporting FDA approval for EPP.
    View source
  2. [2]
    Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo: A Randomized Multicenter Trial
    Lim HW, Grimes PE, Agbai O, et al. · JAMA Dermatology · 2015 · PMID 25471064
    Tier 2 anchor for the vitiligo + phototherapy combination indication.
    View source