What it is
Melanotan I is a lab-made version of α-MSH, a small hormone that tells pigment cells in the skin to make the dark pigment melanin. The natural hormone is short-lived. Changing two of its building blocks made a version that lasts far longer and is much stronger.
Its official drug name is afamelanotide. The only approved product is Scenesse, a tiny rod placed under the skin of the hip every two months. It is approved for people with erythropoietic protoporphyria (EPP), a rare inherited condition in which light on the skin causes severe burning pain. Darker skin is thought to block some of that light.
Injectable powders and nasal sprays sold online as “Melanotan I” for tanning are not Scenesse and are not approved anywhere.
Afamelanotide is [Nle4, D-Phe7]-α-MSH, a linear tridecapeptide amide (C78H111N21O19, 1646.8 g/mol free base). Replacing Met4 with norleucine removes an oxidation-prone residue, and D-phenylalanine at position 7 is thought to stabilise a β-turn in the His-Phe-Arg-Trp core; the 1980 paper reported resistance to serum enzymes. The result is a melanocortin receptor agonist that binds predominantly to MC1R on melanocytes. MC1R is a Gs-coupled receptor; activation raises cAMP and shifts melanogenesis toward eumelanin, which the label describes as occurring independently of UV exposure.
Scenesse is a controlled-release implant of 16 mg afamelanotide in a poly(DL-lactide-co-glycolide) rod. In 12 healthy adults the label reports high variability, a median Tmax of 36 hours, mean Cmax 3.7 ng/mL, an apparent half-life of about 15 hours, and plasma levels measurable to about 96 hours in most subjects. The pigmentary effect outlasts plasma exposure, which is why dosing is every two months. Metabolism is presumed to be hydrolytic and has not been fully characterised.
Who made it and when
The molecule came out of the University of Arizona in Tucson. In 1980 chemist Victor Hruby, biologist Mac Hadley and their colleagues reported that swapping two amino acids in α-MSH made it far more potent and long-lasting. Arizona researchers, including Norman Levine and Robert Dorr, then tested it in people as a sunless tanning agent; it later became known as Melanotan I.
An Australian company, EpiTan, licensed the compound and later renamed itself Clinuvel. Clinuvel moved it away from cosmetic tanning and toward rare light-sensitivity disorders. Europe authorised Scenesse in December 2014, the US FDA approved it on 8 October 2019, and Australia’s regulator followed in October 2020.
Sawyer, Sanfilippo, Hruby, Hadley and colleagues described [Nle4, D-Phe7]-α-MSH in PNAS in 1980, reporting 26-fold greater potency than α-MSH in an adenylate cyclase assay and resistance to serum enzymes. Levine et al. (JAMA 1991) ran a randomised, double-blind, placebo-controlled trial in 28 healthy men showing skin darkening after 10 subcutaneous injections over 12 days, while subjects used a high-potency sunscreen. The name Melanotan II was later given to a separate cyclic analogue from the same group.
Development rights were licensed in 1999 to the Australian company EpiTan, which changed its name to Clinuvel Pharmaceuticals in 2006 (Clinuvel annual report 2006). The EU marketing authorisation (December 2014) was granted under exceptional circumstances because the rarity of EPP limited the data that could be collected. FDA approved NDA 210797 on 8 October 2019 as a new molecular entity. An EU application to extend use to adolescents was withdrawn by the company on 24 April 2024. No compound patent could be verified for this article, so none is listed.
What the data say
Two placebo-controlled trials in EPP, published together in 2015, are the basis of approval. In the US trial, people with the implant spent a median of about 69 hours in direct sunlight without pain over six months, against about 41 hours on placebo. In the European trial, the gap was smaller in hours but the implant group had about half as many painful reactions. Quality-of-life scores improved.
The most common side effects were reactions where the implant goes in, nausea, and darkening of the skin and existing moles. A large trial in vitiligo, a condition where skin loses its colour, finished enrolling in 2025 and had not reported results when this was written; the company has said it expects first results in December 2026.
Langendonk et al. (NEJM 2015) reported two randomised, double-blind, placebo-controlled trials of 16 mg implants every 60 days. CUV039 (US, n=94 randomised) reported median pain-free direct-sunlight time of 69.4 vs 40.8 hours at 6 months (P=0.04); the label reports 64.1 vs 40.5 hours for the same 10 am–6 pm window. CUV029 (EU, n=74, five implants over 270 days) reported 6.0 vs 0.8 hours (P=0.005) and 77 vs 146 phototoxic reactions (P=0.04). Serious adverse events were not considered drug-related.
Across 244 EPP subjects in three vehicle-controlled studies, the label lists implant-site reactions (21% vs 10%), nausea (19% vs 14%), skin hyperpigmentation (4% vs 0%) and melanocytic naevus (4% vs 2%). CUV105 (NCT06109649), an open-label Phase 3 trial of afamelanotide every 3 weeks plus narrowband UVB versus UVB alone in generalised vitiligo (Fitzpatrick skin types III–VI), is active but not recruiting; Clinuvel’s July 2026 SEC filing reported 210 patients enrolled and topline results expected in December 2026. Published case reports link unregulated “melanotan” injections, often of uncertain identity, to changing or new naevi and a small number of melanomas; those reports concern unapproved products, not Scenesse.
Regulatory picture
Three separate facts. Approval: afamelanotide is FDA approved as Scenesse, but only for adults with EPP, and only as an implant placed by a trained professional. It is not approved for tanning, vitiligo or any other use. Compounding: because an approved product exists, pharmacies may not make copies of it. As an ingredient of an approved drug it can legally be used by a US pharmacy in a patient-specific preparation that is not a copy, but such preparations are not reviewed by the FDA. Enforcement: no FDA warning letters naming Melanotan I specifically were found. The powders and sprays sold online as “Melanotan I” are unapproved drugs of unknown content. Australia’s TGA has warned the public against melanotan tanning products, and the UK’s MHRA says it has repeatedly removed melanotan products from sale.
Approval: approved. NDA 210797 (Clinuvel), approved 2019-10-08 for increasing pain-free light exposure in adults with a history of phototoxic reactions from EPP; the latest label revision (08/2024) lists a new contraindication for severe hypersensitivity. The EU authorisation dates from December 2014 and the TGA registration from October 2020.
Compounding: recorded as restricted, meaning copies of Scenesse are not permitted. Because afamelanotide is a component of an FDA-approved drug, section 503A allows it as a bulk ingredient for patient-specific preparations that are not essentially copies; such preparations are not FDA-reviewed. It is not among the peptides FDA placed in Category 2 in 2023. Unapproved injectable or intranasal “Melanotan I” products fall outside both the NDA and any compounding pathway.
International: Australia’s TGA warned in January 2025 that tanning products labelled Melanotan I or II are illegal to supply without a prescription, and the UK’s MHRA stated in a 2021 freedom-of-information response that it had repeatedly acted to remove melanotan products from sale for over 10 years. Habbema et al. (2017) note that multiple national health organisations have issued warnings on melanotan I and II. Those warnings concern unlicensed products, not Scenesse.
