Melanotan I
afamelanotide, Scenesse (brand name of the approved implant), [Nle4, D-Phe7]-α-MSH, NDP-MSH, NDP-α-MSH, CUV1647, MT-I, melanotan-1
1What it is
α-MSH (alpha-melanocyte-stimulating hormone) is a natural 13-amino-acid hormone cut from the larger protein POMC. It tells skin pigment cells to make melanin and has a of minutes. In 1980 a University of Arizona group (Sawyer, Hruby, Hadley) swapped two amino acids and produced an analogue roughly 10–1,000 times more potent and lasting days rather than minutes. Two drug candidates came out of that work: the linear "Melanotan I" and the cyclic "Melanotan II" (profile 44).
Melanotan I was licensed to the Australian company Clinuvel, which developed it as a slow-release implant for erythropoietic protoporphyria (EPP). EPP is a rare inherited disorder in which a light-sensitive chemical (protoporphyrin IX) builds up in the blood and skin, so that minutes of sunlight cause severe burning pain with no visible rash. Scenesse is the first treatment shown to extend how long people with EPP can be in daylight. Afamelanotide is the international non-proprietary name; "Melanotan I" is now mostly used for the grey-market injectable, which has never been shown to contain the approved molecule at the stated dose.
2How it's thought to work
3What the research shows
Erythropoietic protoporphyria
Vitiligo (with phototherapy)
Solar urticaria and polymorphous light eruption
Tanning in healthy volunteers
Actinic keratosis in transplant recipients, Hailey-Hailey disease, arterial ischaemic stroke, xeroderma pigmentosum
4Reported side effects and interactions
Literature-reported
Literature (Scenesse label and trials). headache (~20%), nausea (~19%), implant-site reactions (~21%: bruising, pain, nodules, occasional expulsion or migration of the implant), nasopharyngitis, back pain, skin hyperpigmentation (~10%), darkening of existing moles and new melanocytic naevi, fatigue, dizziness, flushing, hot flush, irritability. The label recommends a full-body skin examination twice a year and caution in people with a history of melanoma. No melanoma signal has been seen in trials or long-term follow-up, but the number of exposed patients is small.
Community-reported
Community-reported (unapproved powder). nausea (especially the first doses), facial flushing, darkening and multiplication of moles and freckles, uneven or "dirty-looking" tan, reduced appetite, fatigue, injection-site redness. Users often cannot distinguish whether their vial is Melanotan I or II.
Theoretical. stimulating pigment cells in people with many or atypical moles, or a personal history of melanoma, is a genuine concern; darkened moles can also hide early melanoma changes from the person and their doctor. Case reports of melanoma in melanotan users mostly involve grey-market product and sunbed use, so causation cannot be assigned.
Interactions. none established; no formal interaction studies (label).
Markers researchers commonly monitor
| Marker | Why it's watched |
|---|---|
| Full-skin examination with dermoscopy and photographic mole mapping at baseline and twice yearly | the label's main monitoring requirement, because moles darken and new naevi appear. |
| Pain-free sunlight exposure time and phototoxic reaction diary (EPP context) | the trial endpoints. |
| Protoporphyrin levels are not expected to change; they track the underlying disease, not the drug | |
| Blood pressure and heart rate | not a signal for afamelanotide, but worth a baseline given the class. |
| No compound-specific blood markers are established; general baselines (CBC, CMP) only |
Free for everyone. Safety information is never behind a paywall.
5Reconstitution and handling
Scenesse is a solid rod inserted by a trained clinician under the skin above the hip; no is involved. Grey-market "Melanotan I" is typically a 10 mg vial, reconstituted with ; the peptide is light-sensitive and should be kept cold and dark.
Open in calculator, pre-loaded →6Commonly studied alongside
Narrowband UVB (vitiligo trials); standard EPP care (light avoidance, protective clothing); Melanotan II is a comparator, not a partner, in community discussion.
Informational cross-links. Not stack recommendations.
7Regulatory status by region
| Region | Status (checked —) |
|---|---|
| United States | FDA-approved October 2019 (Scenesse) for adults with EPP; administered only by trained healthcare professionals. Injectable "Melanotan I" powders are unapproved drugs; FDA has warned against injectable tanning products |
| European Union | EMA-authorised December 2014 (Scenesse) for EPP |
| United Kingdom | MHRA-licensed; NICE recommended afamelanotide for EPP in 2023 †. MHRA has repeatedly warned that injectable melanotans sold online are unlicensed medicines |
| Australia | TGA-registered 2020 (Scenesse) for EPP †; melanotans otherwise Schedule 4, TGA warns against online purchase |
| South Africa | Not registered † |
| Sport (WADA) | Not on the Prohibited List as of review date † |
8Open questions
- Melanoma risk with decades of use; registries are small.
- Adolescents with EPP (trials under way) and other photodermatoses.
- Whether grey-market "Melanotan I" contains afamelanotide at all, and at what dose.
- Can the pigment-independent protective effects be separated from tanning?
9References
- 1Sawyer TK et al. (1980). 4-Norleucine, 7-D-phenylalanine-α-melanocyte-stimulating hormone: a highly potent α-melanotropin with ultralong biological activity. Proc Natl Acad Sci USA. PubMed · DOI
- 2Levine N et al. (1991). Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin. JAMA. PubMed
- 3Dorr RT et al. (2004). Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-α-MSH in humans. Photochem Photobiol. PubMed
- 4Langendonk JG et al. (2015). Afamelanotide for erythropoietic protoporphyria. N Engl J Med. PubMed · DOI
- 5Biolcati G et al. (2015). Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Br J Dermatol. PubMed · DOI
- 6Wensink D et al. (2020). Association of afamelanotide with improved outcomes in patients with erythropoietic protoporphyria in clinical practice. JAMA Dermatol. PubMed · DOI
- 7Lim HW et al. (2015). Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. JAMA Dermatol. PubMed · DOI
- 8Haylett AK et al. (2011). Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle4-D-Phe7]-α-MSH. Br J Dermatol. PubMed · DOI
- 9Böhm M et al. (2005). α-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. J Biol Chem. PubMed · DOI
- 10Scenesse (afamelanotide) US prescribing information and EMA summary of product characteristics (current). PubMed
References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.
† Being confirmed by our reviewers against current sources.
10Community
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Self-reported side effects Phase 2
11Page history
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