Melanotan I and Melanotan II, often written Melanotan 1 and 2, are synthetic analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), the hormone that signals pigment cells in the skin to make melanin. Both came out of the same University of Arizona research group, and both carry the same two changes to the hormone's sequence. Melanotan I keeps the hormone's full length. Melanotan II is a shortened ring.
Their regulatory positions are far apart. Melanotan I is afamelanotide, the active ingredient of Scenesse, which the U.S. Food and Drug Administration (FDA) approved in 2019 for a rare inherited light-sensitivity disorder. Melanotan II has no FDA approval, and it is one of five substances on the agenda of an FDA advisory committee meeting planned before the end of February 2027.
One hormone, two redesigns
- Melanotan I is afamelanotide, CAS 75921-69-6, molecular formula C78H111N21O19. It is the full 13-amino-acid sequence of alpha-MSH with norleucine at position 4 and D-phenylalanine at position 7, a substitution pair Sawyer, Hruby, Hadley and colleagues reported in 1980 as resistant to breakdown by serum enzymes.
- Melanotan II is CAS 121062-08-6, molecular formula C50H69N15O9. It keeps only positions 4 through 10 of the hormone, carries the same two substitutions, and is closed into a ring by a lactam bridge between an aspartate and a lysine.
The difference in size shows in the molecular weights, 1646.8 for Melanotan I and 1024.2 for Melanotan II. A third relative, PT-141 (bremelanotide), is Melanotan II with its C-terminal amide converted to an acid. The FDA approved it in 2019 as Vyleesi for hypoactive sexual desire disorder in premenopausal women.
Different receptor targets
Alpha-MSH acts on a family of melanocortin receptors, numbered MC1 through MC5. MC1R sits on melanocytes, the skin's pigment cells, and drives production of eumelanin, the dark form of melanin.
- Melanotan I: the Scenesse label describes afamelanotide as a melanocortin receptor agonist that "binds predominantly to MC1-R," and says it increases eumelanin in the skin independently of sunlight or artificial UV light.
- Melanotan II: in a 1997 study by Schioth and colleagues on cells expressing single human receptor subtypes, it bound all four receptors tested, MC1, MC3, MC4 and MC5.
That difference set the two development programs apart. In a 2006 review, two members of the Arizona group, Hadley and Dorr, described Melanotan I as tested clinically for skin pigmentation and Melanotan II for the diagnosis and treatment of male erectile dysfunction. Each compound's page covers its receptor evidence in more detail.
The clinical record
Melanotan I has the larger record.
- In 1991, a randomized, placebo-controlled study of 28 healthy men, published in JAMA by the Arizona group, recorded skin darkening only in the men who received the compound.
- Clinuvel later developed it as afamelanotide. Langendonk and colleagues reported two randomized, placebo-controlled Phase 3 trials in erythropoietic protoporphyria (EPP) in the New England Journal of Medicine in 2015, one in the United States and one in Europe, and the FDA label's efficacy section rests on the same two trials.
EPP is an inherited disorder in which light exposure causes painful skin reactions. Melanotan I's page gives the trials' results and the other conditions Clinuvel has studied.
Melanotan II's controlled human record is three small studies from the Arizona group, published between 1996 and 2000.
- Dorr and colleagues, Life Sciences, 1996: a pilot Phase I study in three healthy men that recorded increased pigmentation, spontaneous erections, mild nausea, somnolence and fatigue.
- Wessells and colleagues, Journal of Urology, 1998: a double-blind, placebo-controlled crossover study in ten men with psychogenic erectile dysfunction.
- Wessells and colleagues, Urology, 2000: a crossover study in men with erectile dysfunction and organic risk factors.
ClinicalTrials.gov lists no Phase 3 trial of Melanotan II. The 2006 review named PT-141, Palatin Technologies' analog of Melanotan II, as the compound headed for pivotal Phase 3 trials, and PT-141 is the one that reached approval.
Where FDA stands
Melanotan I:
- December 22, 2014: the European Commission authorized Scenesse under exceptional circumstances, a route the European Medicines Agency uses when complete data on a medicine's benefits cannot be obtained, in this case partly because the disease is rare.
- October 8, 2019: the FDA approved Scenesse (NDA 210797), a dissolving implant from Clinuvel inserted under the skin by a healthcare professional, to increase pain-free light exposure in adults with a history of phototoxic reactions from EPP.
The label warns that afamelanotide may darken existing moles and freckles and recommends a full-body skin examination twice a year. Because afamelanotide is the active ingredient of an approved drug, its U.S. status is set by that approval and sits outside the bulk-substance process that governs most research peptides. Research vials sold as Melanotan I were not made under the Scenesse application.
Section 503A of the Federal Food, Drug, and Cosmetic Act governs compounding by state-licensed pharmacies. A bulk substance with no United States Pharmacopeia (USP) monograph and no place in an approved drug, as with Melanotan II, can be compounded only from FDA's 503A bulks list. While that list is built, FDA sorts nominated substances into categories, and Category 2 holds those it considers may present significant safety risks.
Melanotan II:
- Nominated for the 503A list, it was placed in Category 2.
- April 2026: after the nomination was withdrawn, FDA moved it to the Category 2 page's table of withdrawn nominations. The move is administrative and makes no safety finding.
- That table keeps its safety statement: a risk of immunogenicity, an unwanted immune response, from aggregation or peptide-related impurities, and published case reports of serious adverse events including melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.
- July 2026: it was not among the seven substances the Pharmacy Compounding Advisory Committee heard, and it is not one of the six peptides in the October 2026 Department of Health and Human Services (HHS) policy.
- Before the end of February 2027: FDA has placed it on the committee's next agenda, with LL-37, GHK-Cu, dihexa acetate and pegylated MGF.
The committee vote is advisory, and the 503A list changes only through notice-and-comment rulemaking. Our preview of that meeting covers all five substances.
Names on vendor listings
Vendors abbreviate both names, and the abbreviations collide in one place.
- MT-1, MT1 and "Melanotan 1" refer to Melanotan I, and MT-2, MT2 and "Melanotan 2" to Melanotan II.
- A bare "MT" could be either.
- Afamelanotide is Melanotan I's international nonproprietary name, and Scenesse is the brand of the approved implant alone.
The two molecular weights, 1646.8 and 1024.2, are far enough apart that the mass result on a certificate of analysis (COA) separates them. How to read a peptide COA covers what that test shows.
What they cost
As of November 2, 2026, 29 of the 47 vendors in our index list Melanotan I and 41 list Melanotan II. Median price per milligram for a single vial, one price per vendor:
- Melanotan I 10mg: $3.45 per mg, across 29 vendors.
- Melanotan II 10mg: $3.45 per mg, across 40 vendors.
Nearly every single vial of either is 10mg, and two vendors also sell a 20mg Melanotan II vial. Of the 28 vendors that sell both at 10mg, 19 charge the same price for each, 6 charge more for Melanotan I and 3 charge more for Melanotan II. Three vendors sell Melanotan I as a premixed nasal spray and eight sell Melanotan II that way, priced per bottle and left out of these figures, as are multi-vial kits. Definitions are on the methodology page.
Sources
- PubChem, afamelanotide (CID 16197727): sequence, molecular formula and weight.
- PubChem, melanotan II (CID 92432): structure, molecular formula and weight.
- Sawyer and colleagues, PNAS, 1980: the [Nle4, D-Phe7] analog of alpha-MSH.
- Levine and colleagues, JAMA, 1991: skin darkening in 28 healthy men.
- Dorr and colleagues, Life Sciences, 1996: the pilot Phase I study of Melanotan II.
- Schioth and colleagues, Peptides, 1997: Melanotan II binding at the human MC1, MC3, MC4 and MC5 receptors.
- Wessells and colleagues, Journal of Urology, 1998: Melanotan II in psychogenic erectile dysfunction.
- Wessells and colleagues, Urology, 2000: Melanotan II in organic erectile dysfunction.
- Hadley and Dorr, Peptides, 2006: the two compounds' clinical programs and PT-141.
- Langendonk and colleagues, New England Journal of Medicine, 2015: the Phase 3 trials in EPP.
- FDA, Drugs@FDA record for Scenesse (afamelanotide), NDA 210797: the October 8, 2019 approval.
- Scenesse prescribing information, DailyMed: mechanism, skin monitoring and the clinical trials.
- European Medicines Agency, Scenesse EPAR: the December 22, 2014 authorization under exceptional circumstances.
- FDA, bulk drug substances that may present significant safety risks: Melanotan II among the withdrawn nominations.
- FDA, Meeting of the Pharmacy Compounding Advisory Committee: the meeting planned before the end of February 2027.
- HHS, Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, with its Federal Register notice of availability (91 FR 68526, October 30, 2026).
Prices are as of November 2, 2026, computed from the PeptideScouter index. Sources checked November 2, 2026.