Melanotan 1 vs 2: the difference, and what is approved

Two molecules, one family name

Where the names came from: both were designed in the same academic program to be more potent and more stable than the natural hormone. A 2006 review by two of the chemists involved describes them as a linear peptide, melanotan I, and a cyclic truncated peptide, melanotan II, and records that the first was tested clinically for tanning of the skin and the second for male erectile dysfunction (Hadley and Dorr, 2006). The shared prefix is a laboratory naming convention, not a statement that the two behave alike.

What the approved label prints for the first one: afamelanotide is a synthetic tridecapeptide and a structural analog of alpha-MSH, written Ac-Ser-Tyr-Ser-Nle-Glu-His-(D)Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. That is a straight chain of 13 residues with no ring closure anywhere in it.

What the phase 1 paper prints for the second one: Melanotan 2 is a lactam-bridged cyclic heptapeptide, written Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH2 (Dorr, 1996). A bridge between the aspartate and the lysine locks a fragment of the hormone into a fixed ring.

The row doing the most work is shape: a ring holds the active part of the molecule in one conformation, and conformation is what a receptor either recognizes or does not. The six residues of difference in length are not padding. They are the gap between a chain that can flex and a ring that cannot.

Why does Melanotan 2 do more than tan?

Because it is not aimed at one receptor: the melanocortin family has five receptor subtypes, and the VYLEESI prescribing information lists them all by name when it sets out how far a peptide of this class reaches. MC1R sits on melanocytes, and the SCENESSE label states that afamelanotide increases eumelanin production in skin independently of any exposure to sunlight or artificial ultraviolet light.

The approved label is explicit about its aim: afamelanotide is a melanocortin receptor agonist and binds predominantly to MC1-R. That word, predominantly, is the label's own hedge, and it is doing real work, because predominant is not exclusive.

Melanotan 2 carries no such qualifier: a mouse electrophysiology study in Molecular Metabolism uses it as its non-selective melanocortin receptor agonist, then shows that the effect it was measuring in histamine neurons ran specifically through MC4R (Michael, 2020). MC4R is a central nervous system receptor, not a pigment receptor: the VYLEESI label notes that neurons expressing it sit in many areas of the CNS, and the mouse work ties it to wakefulness and to food intake.

Which predicts what the early human work recorded: the phase 1 study of Melanotan 2 reported pigmentation, and alongside it a stretching and yawning complex, mild nausea, and spontaneous erections lasting intermittently for one to five hours (Dorr, 1996). Those are not skin effects. They are what a molecule reaching past the pigment receptor produces.

Is either one FDA approved?

One is, under its other name: afamelanotide is the active ingredient of SCENESSE, approved under new drug application NDA 210797. The Drugs@FDA record for that application shows the original submission approved on 8 October 2019, and the product listed as an implant for subcutaneous use.

The approval is narrow, and it is not a tanning approval: the label states the product is indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria, a rare inherited photodermatosis. That is the one indication the document carries, and cosmetic tanning is not it.

The other one has no approval to be narrow about: a 2017 review in the International Journal of Dermatology states that afamelanotide is the only alpha-MSH analog approved for use in a limited number of medical indications, and that multiple national health organizations have issued safety warnings covering the unregulated melanotans (Habbema, 2017).

And FDA names Melanotan 2 in its own compounding record: the agency's list of bulk drug substances that may present significant safety risks carries an entry for Melanotan II, in the table of substances nominated for compounding use and then withdrawn by the nominators. The entry cites immunogenicity risk from aggregation or peptide-related impurities, and published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.

How is Melanotan 2 related to bremelanotide?

They are nearly the same ring: the VYLEESI label describes bremelanotide as a synthetic cyclic heptapeptide with the structure Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH). Set that beside the Melanotan 2 structure printed above and the residues run in the same order. What differs is the end of the chain, where bremelanotide terminates in a free acid and Melanotan 2 in an amide.

The lineage is stated in the literature, not inferred by us: the 2006 review calls PT-141 a new Melanotan 2 analog (Hadley and Dorr, 2006), and a 2012 toxicology case report describes bremelanotide as a variation of Melanotan 2 designed specifically for sexual stimulation (Nelson, 2012).

What that buys the comparison: a licensed drug whose label spells out the receptor behavior of this ring shape. VYLEESI states that bremelanotide activates several melanocortin subtypes without selectivity, in the potency order MC1R, MC4R, MC3R, MC5R, MC2R, and that at therapeutic exposure the MC1R and MC4R binding is the part that matters. Read next to the Melanotan 2 observations above, that is the receptor account, printed on an approved label, of why one ring shape moves pigment and central effects together.

Where that story is told properly: the approval itself, the phase 3 endpoints and the limits of what a label covers sit on our page about what the VYLEESI approval covers for PT-141 and bremelanotide, which is a different question from this one.

What has gone wrong in the case reports?

The dermatology signal is about moles, and it covers both: the 2017 review records case reports of cutaneous complications with unregulated use of both Melanotan 1 and Melanotan 2, particularly melanocytic changes in existing moles and newly emerging dysplastic nevi, and counts four case reports describing melanomas emerging from existing moles during or shortly after use. The same review states plainly that conclusive evidence linking the two is lacking (Habbema, 2017).

The clearest single case is a before and after: a 40-year-old man with a history of melanoma and multiple dysplastic nevi self-administered a synthetic alpha-MSH peptide and developed crops of new pigmented nevi, many with atypical clinical and histopathologic features, while his pre-existing nevi darkened and acquired growth features. After he stopped, the nevi progressively lightened and lost those features (Cardones and Grichnik, 2009).

The acute reports belong to Melanotan 2 specifically: a man who injected material bought over the internet presented within hours with tachycardia, sweating, tremor, mydriasis and a rising creatine phosphokinase, and was admitted to intensive care for rhabdomyolysis with renal dysfunction (Nelson, 2012).

Against that, the approved molecule has a long observation record: a pharmacokinetics review reports that no late effects were recorded in volunteers 25 years after first exposure, or after continuous long-term application of up to 8 years in patients with erythropoietic protoporphyria, and states that an immunogenic potential has been excluded (Minder, 2017). That record belongs to a controlled-release implant placed by a clinician, and it does not transfer to a vial of powder bought online.

Which molecule is in the vial?

This is the question the comparison collapses into: everything above assumes the label on the vial is true. Two peptides under one family name, differing by six residues in length, with no pharmacy anywhere in the supply chain, is a setup in which the identity claim is the load-bearing claim, and identity is the one property a buyer cannot see.

What a certificate can and cannot settle: a purity number and an identity number answer different questions. Our page on what HPLC purity does not tell you works through why a high percentage can sit beside the wrong molecule, and the walk-through of how to read a peptide certificate of analysis covers which sections carry identity evidence and which carry none.

And before any of that: the physical thing in the vial is a freeze-dried cake whose appearance reveals very little about its contents, which is the subject of our explainer on what a lyophilized peptide actually is.

What is still unknown?

Three gaps, and none of them is small: the sources on this page settle the chemistry and the regulatory position. They do not settle the questions people are actually asking when they type this comparison into a search box.

• No randomized controlled trial has tested Melanotan 2 for cosmetic pigmentation. The pigment observation in the published record is two of three volunteers in a phase 1 pilot.
• No head-to-head comparison of Melanotan 1 against Melanotan 2 in people appears in the sources assembled for this page, on any endpoint, so every contrast here is a contrast between separate studies in separate populations.
• The melanoma question is open by the reviewers' own account. Case reports establish that pigmented lesions change; they do not establish that a peptide caused a cancer, and the review that counts them says so.

No dataset closes those three today, so no page can cite one.

More from the library

Alongside this comparison: the two compound pages this one deliberately does not duplicate, plus the pages on identity and evidence that sit underneath both of them.

• Melanotan 1 dosage guide: the trial record for the linear molecule, and what the implant label specifies.
• Melanotan 2 dosage guide: what the two human studies reported, and what circulates without one.
• PT-141 and bremelanotide: what the VYLEESI approval actually covers, and what it leaves out.
• How to read a peptide COA: which parts of a certificate carry identity evidence.
• What HPLC purity does not tell you: why a high percentage is not proof of the right molecule.
• What a lyophilized peptide is: what the cake in the vial is, and what its appearance does not prove.

Once a week: one comparison of this kind goes out in the weekly briefing, free.

Sources

What this page is built from: fifteen sources. Two prescribing information documents, one Drugs@FDA application record, one FDA compounding list, six papers reporting human data, one animal pharmacology paper, and four reviews. Every figure above traces to one of them.

How the trial count was arrived at, rather than estimated: we ran PubMed's own Clinical Trial publication-type filter on 2 August 2026 for the query melanotan II, which returns 4 records, and read all four. Three report subjects: Dorr 1996 with 3, Wessells 1998 with 10 and Wessells 2000a with 10. The fourth, Wessells 2000b, reviews the 20 men in the other two. An earlier version of this page said two studies and 13 people, which counted only the two records it happened to cite.

Why both structures are quoted rather than described: the whole comparison rests on the claim that these are two different molecules, so each sequence is printed as its own source writes it, one from an approved label and one from the paper that first put the peptide into people. A reader who wants to check the six-residue difference in length can count it without taking our word for the count.

Why the scope stops where it does: a comparison that reprinted each compound's figures would be competing with the two guides that own them for the same reader, and would put the same numbers in two places to go stale independently. So the two guides keep the numbers and this page keeps the contrast.

The regulatory lines carry a 90-day re-verify date: the FDA compounding entry and the Drugs@FDA record were pulled on 2 August 2026, both HTTP 200. A compounding list is a live document, and a page that quotes one goes stale quietly.

One reference deliberately prints no DOI: the 1998 urology paper resolves to three near-identical Crossref records in the same issue, so rather than pick one and look precise, the entry carries the PubMed record only. Printing a DOI we cannot tie to the article would be the failure this site exists to avoid.

The standard: the full sourcing and verification standard for this site, including who reviews a page before it ships, lives on the methodology page.

Last reviewed: 2 August 2026.

1. 1

   SCENESSE (afamelanotide) implant, for subcutaneous use. Prescribing information, CLINUVEL Inc. Indications and Usage section; Description section, giving the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-(D)Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 and a peptide of 13 amino acids; Clinical Pharmacology section, Mechanism of Action and Pharmacodynamics. SPL version 11, published 13 May 2026. Retrieved 2 August 2026, HTTP 200. DailyMed SPL, set id 94f53286-11dd-7fbb-e053-2a95a90a7c48.

2. 2

   U.S. Food and Drug Administration. Drugs@FDA application record NDA 210797, SCENESSE (afamelanotide), implant, subcutaneous route, listed as a reference drug; original submission approval date 8 October 2019. Read through the openFDA drugsfda endpoint on 2 August 2026, HTTP 200. Drugs@FDA, NDA 210797.

3. 3

   Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48-59. doi:10.1056/NEJMoa1411481. PMID 26132941.

4. 4

   Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84. Source for the lactam-bridged heptapeptide structure, the three volunteers, the pigmentation seen in two of them, and the stretching, yawning, nausea and erection observations. doi:10.1016/0024-3205(96)00160-9. PMID 8637402.

5. 5

   Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998;160(2):389-93. No DOI is printed here on purpose, for the reason set out above this list. PMID 9679884.

6. 6

   Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-646. Cited on this page as Wessells 2000a. Source for the 10 men with organic risk factors, the 12 of 19 against 1 of 21 erection counts, the 45.3 against 1.9 minute rigidity figures and the severe nausea in 4 of 19 injections. doi:10.1016/s0090-4295(00)00680-4. PMID 11018622.

7. 7

   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;12(Suppl 4):S74-S79. Cited on this page as Wessells 2000b. It is the fourth record returned by the PubMed clinical-trial filter, and it reviews the same 20 men as the two crossovers above rather than reporting new subjects, which is why the trial count on this page is three and not four. doi:10.1038/sj.ijir.3900582. PMID 11035391.

8. 8

   Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-30. Source for the description of Melanotan 1 as a linear peptide and Melanotan 2 as a cyclic truncated peptide, for what each was tested clinically for, and for PT-141 as a melanotan II analog. doi:10.1016/j.peptides.2005.01.029. PMID 16412534.

9. 9

   Michael NJ, Caron A, Lee CE, et al. Melanocortin regulation of histaminergic neurons via perifornical lateral hypothalamic melanocortin 4 receptors. Mol Metab. 2020;35:100956. A mouse electrophysiology study, cited here only for its description of melanotan II as a non-selective melanocortin receptor agonist and for the MC4R-mediated effect it reports. doi:10.1016/j.molmet.2020.01.020. PMID 32244183.

10. 10

    Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017;56(10):975-980. Source for afamelanotide as the only approved alpha-MSH analogue, for the melanocytic and dysplastic nevus case reports, for the count of four melanoma case reports, for the statement that conclusive evidence is lacking, and for national health organization warnings. doi:10.1111/ijd.13585. PMID 28266027.

11. 11

    Cardones AR, Grichnik JM. alpha-Melanocyte-stimulating hormone-induced eruptive nevi. Arch Dermatol. 2009;145(4):441-4. doi:10.1001/archdermatol.2008.623. PMID 19380666.

12. 12

    Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-73. Source for the sympathomimetic presentation, the rhabdomyolysis and renal dysfunction, and for the description of bremelanotide as a variation of Melanotan II designed for sexual stimulation. doi:10.3109/15563650.2012.740637. PMID 23121206.

13. 13

    Minder EI, Barman-Aksoezen J, Schneider-Yin X. Pharmacokinetics and pharmacodynamics of afamelanotide and its clinical use in treating dermatologic disorders. Clin Pharmacokinet. 2017;56(8):815-823. Source for MC1R binding and its downstream effects, for the absence of late effects in volunteers 25 years after first exposure and after continuous long-term application of up to eight years in erythropoietic protoporphyria, and for the exclusion of an immunogenic potential. doi:10.1007/s40262-016-0501-5. PMID 28063031.

14. 14

    VYLEESI (bremelanotide injection), for subcutaneous use. Prescribing information, Cosette Pharmaceuticals, Inc. Description section, giving the structure Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH); Clinical Pharmacology section, Mechanism of Action, giving the non-selective activation order MC1R, MC4R, MC3R, MC5R, MC2R and the note that neurons expressing MC4R are present in many areas of the central nervous system. SPL version 1, published 18 November 2025. Retrieved 2 August 2026, HTTP 200. DailyMed SPL, set id f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf.

15. 15

    U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks, table headed "Bulk drug substances nominated but withdrawn", entry "Melanotan II", naming immunogenicity risk from aggregation or peptide-related impurities and published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism. Content current as of 22 April 2026. Retrieved 2 August 2026, HTTP 200. fda.gov, category 2 and withdrawn nominations.