Melanotan I

Origin and structure

Alpha-MSH (alpha-melanocyte-stimulating hormone) is a 13-amino-acid hormone that signals pigment cells to make melanin. In 1980 a University of Arizona group that included Victor Hruby and Mac Hadley reported that changing two of its building blocks, methionine at position 4 for norleucine and phenylalanine at position 7 for its mirror-image form D-phenylalanine, gave a peptide that resisted the serum enzymes that break the natural hormone down and was 26 times as potent in a cell assay. The result, [Nle4, D-Phe7]-alpha-MSH, is also written NDP-MSH.

Under the name Melanotan I the Arizona researchers tested it as a sunless tan that might lower the risk of skin cancer; a shorter, ring-shaped relative from the same programme became Melanotan II. Clinuvel later took Melanotan I into clinical development under the code CUV1647 and the name afamelanotide. Its sequence is Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, with the formula C78H111N21O19 and a molecular weight of about 1647.

How it works

Afamelanotide activates melanocortin receptors and binds mainly to MC1R, the receptor on pigment cells (melanocytes) that switches on production of eumelanin, the dark brown-black form of melanin. Eumelanin absorbs ultraviolet and visible light and neutralises free radicals, so the darker skin it produces acts as a filter without UV damage having to come first. The darkening fades gradually unless the peptide is given again.

People with EPP have high levels of protoporphyrin IX, a substance that reacts to light and causes painful reactions and swelling of the skin. More eumelanin means less light gets through to it, which is why the trials measured pain-free time in sunlight rather than skin colour.

The peptide on its own has a half-life of about 30 minutes, so the medicine is a slow-release rod of biodegradable polymer, about 1.7 cm long. Most of the dose is released in the first 48 hours and more than 90% by day 5, and the rod is absorbed within 50 to 60 days. Measured from the implant, the FDA label gives an apparent half-life of about 15 hours; in 9 of 12 volunteers the last measurable blood level was at 96 hours.

Is Melanotan I approved?

Yes, but in one form and for one disease. The European Commission authorised Scenesse, Clinuvel's afamelanotide implant, on 22 December 2014 to prevent phototoxicity in adults with EPP. The authorisation was granted under exceptional circumstances, because the disease is too rare for complete data, and the EMA reviews new information every year. It is a medicine on restricted prescription: only specialists at recognised porphyria centres may prescribe it, and the implant is placed by a doctor trained by the manufacturer. Its orphan-medicine status ended in December 2024. An application to extend it to adolescents, narrowed during assessment to 15- to 17-year-olds weighing over 60 kg, was withdrawn on 24 April 2024 after the EMA's provisional view was that it could not be approved.

The EU authorisation covers the Netherlands. The published Dutch experience with the medicine comes from Erasmus MC in Rotterdam, which treated 117 patients between 2016 and 2018 in a post-authorisation study directed by the EMA, described below.

In the United States the FDA approved Scenesse on 8 October 2019 to increase pain-free light exposure in adults with a history of phototoxic reactions from EPP. Neither regulator has approved afamelanotide for cosmetic tanning, vitiligo or any other use. Tanning products sold as Melanotan I or II are not authorised medicines, and a review by Dutch dermatologists notes that several national health authorities have warned against them.

In sport, afamelanotide is not named anywhere on the 2026 WADA Prohibited List, which the Dutch anti-doping rules apply. Because it is an approved medicine it does not fall under class S0, the catch-all for substances without any approval for human use, which is where Melanotan II, never authorised as a medicine, falls.

What the research shows

Afamelanotide has a real human evidence base: randomised trials in EPP that led to its approval, small controlled trials in healthy volunteers, and controlled trials in vitiligo. What is missing is any study of the unregulated injections sold for tanning.

• First tanning trial (Levine et al., 1991): a randomised, placebo-controlled trial in 28 healthy white men in Arizona, who used a high-protection sunscreen throughout. Skin darkened on the active injections, in poor and good tanners alike, and not on saline; the effect peaked 1 to 3 weeks after the last injection.
• Pigment and UV protection (Barnetson et al., 2006): 65 fair-skinned volunteers completed a placebo-controlled trial. Skin melanin rose by an average of 41% in those who burn easily and by 12% in those who burn less. Sunburn cells after a UV test dose fell by more than half in the burn-prone group, and DNA damage (thymine dimers) in the basal skin layer was 59% lower after treatment.
• EPP, the two pivotal trials (Langendonk et al., 2015): 168 adults were randomised to implants or placebo every 60 days. In the US trial (94 patients, 6 months) the median pain-free time in direct sunlight was 69.4 hours against 40.8 hours on placebo; in the EU trial (74 patients, 9 months) it was 6.0 against 0.8 hours, with 77 phototoxic reactions against 146. Quality of life improved in both. The FDA's own analysis of the US trial gives medians of 64.1 and 40.5 hours.
• EPP in Dutch practice (Wensink et al., 2020): of 117 patients treated at Erasmus MC between 2016 and 2018, 115 (98%) stayed on treatment over a median follow-up of 2 years. Time spent outside rose by 6.1 hours a week and the disease-specific quality-of-life score by 14%. Reactions were less painful, but their number and duration did not change. This was a cohort without a control group.
• Vitiligo, phase 2 (Lim et al., 2015): 55 adults with skin types III to VI were randomised to narrowband UV-B phototherapy alone or with afamelanotide implants. By day 168, repigmentation averaged 48.6% with the combination against 33.3% with UV-B alone, and the face and arms began to repigment sooner. The benefit was seen in skin types IV to VI, not in type III.
• Vitiligo, phase 3 (CUV105, NCT06109649): an open-label trial of implants plus UV-B against UV-B alone, planned for 200 patients aged 12 and over at sites in the US, France, the UK and Kenya. It has stopped recruiting and had posted no results by October 2026.
• Smaller trials registered by Clinuvel have tested it in polymorphic light eruption (18 and 31 patients), solar urticaria (5), variegate porphyria (6), acne (3) and acute stroke (6); two trials in xeroderma pigmentosum, each planned for 6 patients, have no reported outcome. None has led to an approved use.

Melanotan I versus Melanotan II

The names suggest two versions of one product, but they are different molecules. Melanotan I is the linear 13-amino-acid peptide described above, which binds mainly to the pigment receptor MC1R. Melanotan II is a shorter, ring-shaped peptide from the same Arizona programme. It also darkens skin, but its clinical tests focused mainly on erectile dysfunction; a derivative of it, PT-141 (bremelanotide), was developed for sexual dysfunction and has its own article in this wiki.

Only Melanotan I became an authorised medicine, and only as a slow-release implant for EPP. Both circulate as unlicensed tanning injections. A 2017 review by Dutch dermatologists found growing numbers of case reports of changes in existing moles and new, sometimes atypical moles after use of either, and four reports of melanoma arising from an existing mole during or shortly after use. It judged a causal link unproven, but considered the products risky because their preparation, dose and administration are uncontrolled.

Research-grade Melanotan I contains the same peptide as Scenesse, but it is not the same product: Scenesse is a slow-release implant made and authorised under EU and US medicines rules, while research material has not been assessed or authorised as a medicine.

Frequently asked questions

Is Melanotan I the same as afamelanotide and Scenesse?

Melanotan I and afamelanotide are two names for the same molecule. Scenesse is the medicine: a slow-release afamelanotide implant, authorised in the EU and the US for adults with erythropoietic protoporphyria and placed under the skin by a trained doctor. Research-grade or online Melanotan I contains the same peptide but has not been assessed or authorised as a medicine.

Is Melanotan I legal in the Netherlands?

As the medicine Scenesse it is authorised in the Netherlands through the EU authorisation, on restricted prescription by specialists at recognised porphyria centres; the published Dutch experience with it comes from Erasmus MC in Rotterdam. Any other product offered for use in people, such as a tanning injection, is not an authorised medicine, so it may not be sold, supplied or advertised for that purpose. Buying and selling it as research material is a different status, which our guide on research-use-only products in the Netherlands explains.

Is Melanotan I banned in sport?

It is not named on the 2026 WADA Prohibited List, which the Dutch anti-doping rules apply. Because afamelanotide is an approved medicine it does not fall under S0, the class for substances without any approval for human use. It is not listed under the peptide-hormone class S2 either, but that class also covers substances with a similar structure or effect, so athletes who want certainty can ask the Dopingautoriteit.

Does Melanotan I cause skin cancer?

There is no evidence that afamelanotide causes skin cancer, but the question is not settled. It has not been studied for longer than two years, no carcinogenicity studies exist, and the labels ask for a full-body skin examination every six months because it darkens existing moles and freckles. One trial in fair-skinned volunteers found less UV damage after treatment, not more. With unregulated melanotan products, a 2017 Dutch review counted four case reports of melanoma during or shortly after use, without proof that the product was the cause.

Does Melanotan I tan without sun?

In small trials, yes. In a 1991 placebo-controlled trial in 28 men who used sunscreen throughout, skin darkened after a course of injections and peaked one to three weeks after the last one, and in a 2006 trial in 65 fair-skinned volunteers skin melanin rose by an average of 41% in those who burn easily. No regulator has approved it for tanning, and these trials did not test the products sold online.

What is the difference between Melanotan I and Melanotan II?

They are different molecules from the same Arizona research programme. Melanotan I is a linear 13-amino-acid peptide that binds mainly to the pigment receptor MC1R and became the authorised medicine Scenesse. Melanotan II is a shorter, ring-shaped peptide that also darkens skin, was tested in the clinic mainly for erectile dysfunction, and has never been authorised as a medicine; its derivative PT-141 (bremelanotide) was developed for sexual dysfunction.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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