OtherEvidence A2 cited

Melanotan I

aka Melanotan I · MT-1 · Afamelanotide · Scenesse · NDP-MSH

A synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH) that activates MC1R for photoprotection. EMA-approved (Scenesse) for erythropoietic protoporphyria (EPP). The most regulatory-advanced melanocortin peptide.

Molecular wt

1646.85 (anhydrous free base; PubChem computes 1646.8)g/mol

Formula

C78H111N21O19

CAS

75921-69-6

Half-life

30 min

established

Tmax

1.5 h

Route

Subcutaneous injection

PubChem

16197727

Sequence

Read this before quoting the sequence

13-residue linear alpha-MSH analogue, N-terminally acetylated and C-terminally amidated. Contains non-proteinogenic residues (norleucine at position 4, D-phenylalanine at position 7), so a standard one-letter string is not applicable. Identical to the approved drug afamelanotide (SCENESSE). Sequence taken verbatim from the FDA label DESCRIPTION section and matches the PubChem depositor synonym 'Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2'.

Source ↗

Mechanism of action

Melanotan I (afamelanotide) is a potent and selective MC1R agonist. It stimulates melanogenesis (eumelanin production) in melanocytes, providing photoprotection against UV radiation. Unlike Melanotan II, it has minimal activity at MC3R, MC4R, and MC5R, resulting in a cleaner side effect profile without significant appetite suppression or sexual side effects.

What the evidence actually shows

Grade A

EMA-approved (Scenesse) for EPP. Phase 3 clinical trials completed. The most evidence-based melanocortin peptide with regulatory approval in Europe.

Regulatory status

Status

Approved as a prescription medicine under the name afamelanotide (SCENESSE). Not approved, and not legally marketed, as 'Melanotan I' research powder.

Approved as

SCENESSE (afamelanotide) 16 mg subcutaneous implant, indicated to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). EU marketing authorisation 22 December 2014 (under exceptional circumstances); US FDA approval under NDA 210797, label dated 2019.

Clinical stage

Approved (EU and US) for EPP.

Source ↗

Pharmacokinetics

Half-life

30 min

Tmax

1.5 h

Absorption

subcutaneous

Elimination

renal

Washout

1 days

Low-confidence pharmacokinetics

These figures are recorded as established rather than measured in a published PK study. Treat them as an order of magnitude. Anything downstream of them — accumulation, steady state, washout — inherits that uncertainty.

Dosing — what backs each figure

Melanotan I is afamelanotide, an approved drug (SCENESSE, FDA 2019 / EMA 2014) with a real labelled regimen: one 16 mg subcutaneous implant every 2 months, placed by a trained clinician, for erythropoietic protoporphyria. Injectable milligram-per-day 'loading' schedules sold to consumers correspond to nothing in the approved label or the published human pharmacokinetic literature.

ClinicalApproved labelling or a published human trial

16 mg afamelanotide as a single subcutaneous implant inserted above the anterior supra-iliac crest, every 2 months (max 6 implants/year); administered by a trained healthcare professional
adults with erythropoietic protoporphyria (EPP) with a history of phototoxic reactions · subcutaneous implant
FDA prescribing information, SCENESSE (afamelanotide) implant, NDA 210797 (2024 revision) ↗
16 mg afamelanotide subcutaneous implant every 60 days; 5 implants (EU study) or 3 implants (US study)
EPP patients, two multicentre randomised double-blind placebo-controlled trials (74 EU, 94 US) · subcutaneous implant
Langendonk JG et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med 2015;373:48-59 ↗
Melanotan-I ([Nle4-D-Phe7]-alpha-MSH) 0.08-0.21 mg/kg subcutaneously, 0.16 mg/kg intravenously and 0.16 mg/kg orally, one dose daily for 10 doses over 2 weeks (crossover); oral route gave no detectable plasma levels
3 healthy male volunteers, pharmacokinetic/pigmentation crossover trial · subcutaneous / intravenous / oral
Dorr RT et al. Skin pigmentation and pharmacokinetics of melanotan-I in humans. Biopharm Drug Dispos 1997;18:23-33 ↗

Commonly circulatedNot established by any study

Dose: Research literature cites ~0.5 to 1 mg/day loading

Why this isn't evidence
No published human study or label uses a 0.5-1 mg/day loading regimen: the approved product is a 16 mg implant every 2 months, and the only published subcutaneous human dosing was 0.08-0.21 mg/kg per dose (roughly 6-15 mg for a 70 kg adult), so the ported figure matches neither and no loading phase or cycle appears in any source.

This figure is shown because it is what circulates and what people search for — not because it is supported. Cycle lengths in particular tend to be convention copied between compounds rather than anything derived from a compound's own pharmacokinetics.

Handling and storage

No compound-specific stability data exists

No published stability data for lyophilised or reconstituted research-grade Melanotan I powder was located. The only compound-specific storage instruction that could be sourced is for the approved product SCENESSE (afamelanotide 16 mg subcutaneous implant): 'Store in a refrigerator at 2 degrees C - 8 degrees C (36 F-46 F). Protect from light.' That instruction applies to a solid implant, not to a reconstituted solution, and should not be read across to vialled powder. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.

→ Reconstitution walkthrough → Reconstitution calculator

Safety

Contraindications

·Melanoma or atypical naevi

Nausea, flushing, darkening of naevi

References (2)

Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, et al. (2015) Afamelanotide for Erythropoietic Protoporphyria ↗
N Engl J MedPMID 26132941DOI
Two randomised, placebo-controlled trials of subcutaneous afamelanotide implants in erythropoietic protoporphyria; the implant increased pain-free sun exposure time versus placebo. This is the pivotal human evidence base for the approved drug.
Wu J, Cotliar R. (2021) Afamelanotide: An Orphan Drug with Potential for Broad Dermatologic Applications ↗
J Drugs DermatolPMID 33683075DOI
Review of afamelanotide covering its approved EPP indication and investigational dermatologic uses; narrative review, not primary data.

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
storage.lyophilized, storage.reconstituted, reconstitution.solvent, regulatory.wada

Research use only

This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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