what is the difference
Melanotan I and melanotan II
Two names one digit apart, attached to two molecules whose published records were built for entirely different questions.
Melanotan I is afamelanotide, a thirteen amino acid analog of alpha-melanocyte-stimulating hormone and the closest of these compounds to the natural hormone. It holds an FDA approval under the brand name Scenesse, granted in October 2019, to reduce phototoxicity in adults with erythropoietic protoporphyria, a rare inherited disease in which sunlight causes severe pain. The approved product is an implant placed under the skin by a trained specialist rather than anything a person handles, and its labelling is published in the FDA labelling database DailyMed [11].
Melanotan II is a seven amino acid ring-shaped analog of the same hormone, less selective across the melanocortin receptors, and a separate molecule rather than a version of the first. It holds no approval anywhere and DailyMed returns no label under the name melanotan, searched on 2 August 2026 [11]. Both are sold for the same cosmetic purpose, and only one has been through a randomised trial of anything.
Not medical advice
This page reports what has been documented about a compound. It is not medical advice, not a diagnosis, not a dosing protocol, and not a recommendation to obtain or use anything described here. Talk to a licensed clinician about anything concerning your health. Read the full disclaimer.
Reviewed against editorial standards Updated
The short answer
The approval belongs to melanotan I, and it belongs to a specific product, in a specific rare disease, delivered in a specific form. Melanotan II has one registered study, in vitiligo, which is recruiting and has posted nothing.
Neither approval nor registration touches the use both compounds are actually sold for. No published study of any design has tested either molecule for a cosmetic tan, so the strong trial record on one side of this pair answers a question nobody buying it was asking.
Side by side
| Property | Melanotan I | Melanotan II |
|---|---|---|
| What it is | Afamelanotide, a thirteen amino acid linear analog of alpha-melanocyte-stimulating hormone | A seven amino acid cyclic analog of the same hormone, and a separate molecule rather than a variant of melanotan I |
| Selectivity across the melanocortin receptors | More selective, and structurally the closer of the two to the natural hormone | Less selective, which is why accounts of it describe effects beyond pigmentation |
| Other names | Afamelanotide, Scenesse | MT-2, MT-II |
| Regulatory position | FDA approved as Scenesse in October 2019 to reduce phototoxicity in adults with erythropoietic protoporphyria. Labelling published in DailyMed | No approval anywhere. DailyMed returns no label under the name melanotan, searched 2 August 2026 |
| Form of the approved product | An implant placed under the skin by a trained specialist, in a hospital or specialist setting | No approved product exists, so there is no approved form |
| Registrations on ClinicalTrials.gov | 23 under afamelanotide, across phase 2 and phase 3 | 1, NCT07437560, a phase 2 study alongside narrowband UVB phototherapy for stable non-segmental vitiligo, recruiting with nothing posted |
| Published trial record | A randomised multicentre trial in the New England Journal of Medicine in 2015, measuring pain-free time in sunlight in erythropoietic protoporphyria, plus a long-term observational study following 115 patients with the same disease | One paper, from 2000, in which the authors reviewed their own double-blind, placebo-controlled crossover experience in 20 men with erectile dysfunction |
| Published case-report literature | Included in the same dermatology review that covers melanotan II, where reports of melanocytic change are described for both | Eight published reports: three of pigmented lesions, one of new and darkening moles, and four of events outside the skin |
| What the trial record is about | An implanted product in a rare inherited light-sensitivity disease, in a population diagnosed with it | Erectile response in 20 men, measured a quarter of a century ago |
| What is actually sold | Injected material under the research name melanotan I, which is not the approved implant | Injected material for a cosmetic tan |
| What no published study has tested | Cosmetic tanning, by any route, in anyone | Cosmetic tanning, by any route, in anyone |
| Regulator attention | Approved under one brand name and one indication, and named in a 2017 dermatology review among the compounds national health organisations have warned about | Named in the same review, which records warnings from multiple national health organisations |
Why the two get mixed up
The names are one character apart and the compounds are not. Melanotan I is thirteen amino acids in a line and melanotan II is seven amino acids in a ring, which in peptide terms is a bigger difference than the shared name suggests. They act on the same receptor family with different selectivity, and only one of them ever went through a drug development programme.
The published harm literature does most of the damage, because of how it is titled. Four of the case reports on melanotan II carry the bare word melanotan with no numeral: melanotan-associated melanoma [3], melanotan-associated melanoma in situ [5], melanotan and the posterior reversible encephalopathy syndrome [6], and melanotan-induced priapism [8]. A reader searching either name lands on all of them, and a title alone cannot say which molecule a report concerns. Reading the papers is the only way, and this page did that.
Then the approval gets moved. Melanotan I holds a real FDA approval, and a product page for either compound can quote it accurately and still mislead completely. The approval covers an implant, placed by a specialist, to reduce phototoxicity in a rare inherited disease. It does not reach a cosmetic tan, it does not reach injected material sold under a research name, and it does not reach melanotan II at all.
What the published record covers for each
The melanotan I record is what an approval of this kind looks like. A randomised multicentre trial published in the New England Journal of Medicine in 2015 tested the implant in patients with erythropoietic protoporphyria and measured pain-free time spent in sunlight [Human RCT] [1]. A separate long-term observational study followed 115 patients with the same disease through repeated treatment and reported what happened over that period [Human open-label] [2]. Both are about one disease, one population and one implanted product.
The melanotan II record is a single old study and a set of case reports. The 2000 paper reported penile erection in 17 of 20 men with erectile dysfunction under a double-blind, placebo-controlled crossover design, along with frequent nausea and yawning; PubMed indexes it as a controlled clinical trial rather than a randomised one, so it carries the open-label tier here [Human open-label] [9].
Three of the case reports concern pigmented lesions, which is the cluster that matters most in a compound taken for pigmentation. A melanoma reported in the British Journal of Dermatology [3], a melanoma associated with melanotan-II reported in Dermatology [4], and a melanoma in situ reported in the Australasian Journal of Dermatology [5], each in a person who had injected it for a cosmetic tan [Anecdote]. A fourth report describes eruptive naevi together with darkening of pre-existing naevi, 24 hours after a single injection [Anecdote] [10]. Darkening of an existing mole is among the earliest visual changes dermatologists look for, which is why this group of reports draws the attention it does.
Four further reports describe events outside the skin. Posterior reversible encephalopathy syndrome, a brain condition visible on imaging, in the Annals of Internal Medicine [6]; renal infarction, a blocked blood supply to a kidney, in CEN Case Reports [7]; priapism, a prolonged and painful erection, in BMJ Case Reports [8]; and systemic toxicity with rhabdomyolysis, the breakdown of muscle tissue, in Clinical Toxicology [12] [Anecdote]. Each of those is one person or a small series. A case report has no denominator behind it, so nothing in this group establishes how often any of it happens.
A 2017 review in the International Journal of Dermatology gathers the position across both compounds. It records that case reports associate the unregulated use of melanotan I and melanotan II with melanocytic change in existing moles and with new dysplastic naevi, that four reports at that time described melanomas emerging from existing moles during or shortly after use, that conclusive evidence linking the two is lacking, and that multiple national health organisations have issued safety warnings about both compounds [13].
Our takeOne number apart, and the records were built for different questions. The melanotan I trials are strong evidence about a rare inherited disease and an implanted product, and the melanotan II literature is eight case reports and a paper from 2000. Neither addresses a tan.
Frequently asked questions
Is melanotan I just a weaker version of melanotan II?
They are two different molecules. Melanotan I is afamelanotide, thirteen amino acids in a line, more selective across the melanocortin receptors and structurally the closer of the two to the natural hormone. Melanotan II is seven amino acids in a ring and less selective. Neither is a variant of the other, and their published records were built for different questions.
Which one is FDA approved?
Afamelanotide is, as Scenesse, granted in October 2019 to reduce phototoxicity in adults with erythropoietic protoporphyria, and its labelling is published in DailyMed [11]. The approved product is an implant placed under the skin by a trained specialist. Melanotan II holds no approval anywhere, and DailyMed returned no label under the name melanotan when it was searched on 2 August 2026 [11].
Does the melanotan I approval say anything about tanning?
It covers phototoxicity in a rare inherited disease, in adults diagnosed with it, using an implanted product. Cosmetic tanning is a different question, in a different population, by a different route, with a different endpoint, and no published study of any design has tested it for either compound. The approval quoted on a tanning product page is a genuine approval answering a question it never addressed.
What do the melanotan II case reports actually describe?
Three describe pigmented lesions in people who had injected it for a tan: a melanoma [3], a melanoma associated with melanotan-II [4] and a melanoma in situ [5]. A fourth describes eruptive naevi and darkening of existing naevi 24 hours after a single injection [10]. Four more describe posterior reversible encephalopathy syndrome [6], renal infarction [7], priapism [8] and systemic toxicity with rhabdomyolysis [12]. Each is one person or a small series, and none of them supplies a rate.
Why do so many of the papers just say melanotan?
Because the case reports were titled that way. Four of them carry the bare word with no numeral [3] [5] [6] [8], so a search on either name returns all of them and a title alone cannot tell you which molecule a report concerns. That is the single most reliable way this literature gets attributed to the wrong compound, and the only fix is to read the papers.
Have regulators said anything about these?
A 2017 review in the International Journal of Dermatology records that multiple national health organisations have issued safety warnings about melanotan I and melanotan II, and that the only analog of this hormone approved for medical indications is afamelanotide [13]. This site reports that through the review because it has not fetched and dated the individual agency notices, and an agency action gets named here with its document and its date or not at all.
References
- Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FPJ, Sijbrands EJG, de Rooij FWM, Lebwohl M, Naik H, Goding CR, Wilson JHP, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015. PMID 26132941 DOI 10.1056/NEJMoa1411481
- Biolcati G, Marchesini E, Sorge F, Barbieri L, Schneider-Yin X, Minder EI. Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Br J Dermatol. 2015. PMID 25494545 DOI 10.1111/bjd.13598
- Paurobally D, Jason F, Dezfoulian B, Nikkels AF. Melanotan-associated melanoma. Br J Dermatol. 2011. PMID 21564053 DOI 10.1111/j.1365-2133.2011.10273.x
- Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014. PMID 24355990 DOI 10.1159/000356389
- Ong S, Bowling J. Melanotan-associated melanoma in situ. Australas J Dermatol. 2012. PMID 22724573 DOI 10.1111/j.1440-0960.2012.00915.x
- Kaski D, Stafford N, Mehta A, Jenkins IH, Malhotra P. Melanotan and the posterior reversible encephalopathy syndrome. Ann Intern Med. 2013. PMID 23648958 DOI 10.7326/0003-4819-158-9-201305070-00020
- Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020. PMID 31953620 DOI 10.1007/s13730-020-00447-z
- Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019. PMID 30796078 DOI 10.1136/bcr-2018-227644
- Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000. PMID 11035391 DOI 10.1038/sj.ijir.3900582
- Schulze F, Erdmann H, Hardkop LH, Anemüller W, Rose C, Zillikens D, Fischer TW. Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose injection of melanotan II. Eur J Dermatol. 2014. PMID 24334249 DOI 10.1684/ejd.2013.2227
- US National Library of Medicine, DailyMed. SCENESSE (afamelanotide) implant prescribing information, as published in the FDA labelling database. Searched 2 August 2026, when the same database returned no label under the name melanotan. DailyMed, National Library of Medicine. 2026. DailyMed label
- Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012. PMID 23121206 DOI 10.3109/15563650.2012.740637
- Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017. PMID 28266027 DOI 10.1111/ijd.13585