Entry 0026Rev 1.0Cyclic melanocortin agonist

Melanotan II

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 · C50H69N15O9

Reviewed

2 Nov 2026

Scientific editor

[Name, PhD]

References

50 sources

Melanotan II is a cyclic seven-residue copy of the core of alpha-melanocyte-stimulating hormone, designed at the University of Arizona in 1989 to be more potent and longer-lasting than the hormone. It acts on several melanocortin receptors, which control pigment, appetite and sexual function.1,3

Three small human studies in the 1990s measured skin darkening and erections. Development then moved to its free-acid relative, bremelanotide. Melanotan II itself is not licensed anywhere, and UK, US and Australian regulators have all warned against unlicensed tanning products that contain it.4,12,47

Residues

7, cyclic

Avg mass

1024.2 g/mol

Human studies

3, 1990s

Licensed

Nowhere

01

Identity

Value
SequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2; a lactam bridge joins Asp and Lys to close the ring
Based onAlpha-MSH residues 4–10, with norleucine for methionine and D-phenylalanine for phenylalanine
ReceptorsMC1R (pigment), MC3R, MC4R (appetite, sexual function), MC5R
FormulaC50H69N15O9
Avg mass1024.2 g/mol
CAS121062-08-6
RelativesBremelanotide (PT-141) is the same ring with a free acid instead of the amide, licensed in the US. Afamelanotide (Melanotan I) is a linear 13-residue analogue, licensed in the EU and US for a rare light-sensitivity disorder.
02

History

  1. Designed and made at the University of Arizona; about 90 times the potency of alpha-MSH in a lizard-skin assay.1,3

  2. Pilot study in three men: skin darkened, with nausea, tiredness, yawning and spontaneous erections.9

  3. Placebo-controlled crossover in ten men with erectile dysfunction: erections in eight.10

  4. Palatin drops Melanotan II and develops the free-acid version, bremelanotide, instead.4

  5. US FDA warning letter to a company selling it online as a tanning agent.50

  6. UK MHRA warns that Melanotan is an unlicensed injectable sold through websites, gyms and tanning salons.50

  7. First reports of changing moles in users published in the BMJ.12

  8. Australia makes it prescription-only.47

  9. US FDA places it in its significant-safety-risk category for compounding; later recorded as withdrawn by the nominators.46

03

What the studies measured

The human studies are small and all from one programme. The animal work established the appetite and erection effects that the melanocortin field is built on.

StudyModelWhat was measuredFindingSource
Al-Obeidi 1989Frog and lizard skinPigment darkening against alpha-MSHAbout 90-fold more potent, with prolonged activity[1],[3]
Fan 1997MiceFood intake after injection into the brainFeeding fell in four models of overeating; blocked by a receptor antagonist[14]
Dorr 19963 healthy men, placebo-alternatingSkin pigment by reflectance; side effectsDarkening in two of three; nausea, tiredness, erections[9]
Wessells 199810 men with psychogenic erectile dysfunction, crossoverErections by RigiScan over 6 hoursErections in 8 of 10; rigid for 38 minutes against 3 on placebo[10]
Wessells 200010 men with organic erectile dysfunction, crossoverErections, desireErections after 12 of 19 active doses against 1 of 21 placebo; severe nausea after 4[11]
Breindahl 2015Vials bought onlineContent and purity by LC-MS43% to 88% of the labelled amount; unknown impurities up to 5.9%[17]
04

Reported harms

These are published case reports in people using unlicensed products, often with sunbeds and other drugs. They show association, not proof of cause, but they are why regulators have acted.

ReportWhat was describedSource
MolesNew or rapidly changing moles in users; several reports from 2009 onwards[12],[18],[19]
MelanomaMelanoma in users, including one 20-year-old sunbed user and a 2025 oral melanoma after nasal-spray use; a 2017 review found the link unproven[24],[26],[27],[29]
Muscle breakdownRhabdomyolysis with kidney injury after injection of a product confirmed as Melanotan II[30]
KidneyRenal infarction[31]
BrainPosterior reversible encephalopathy syndrome[32]
PriapismProlonged erection needing treatment, three reports[33],[34],[35]

In 2013 the MHRA said it held 18 Yellow Card reports describing 74 suspected reactions, and had closed 72 websites in three months.50

05

Regulatory and sport status

As of this revision. General information, not legal advice.

WhereStatus
UKUnlicensed. The MHRA has warned against it since 2008 and has acted against sellers; nasal "tanning sprays" drew Trading Standards warnings in 2025. May not be supplied or promoted for human use.50
EUNo authorisation. Its relative afamelanotide (Scenesse) is licensed for a rare light-sensitivity disorder.45
USNot approved. FDA warning letter in 2007; placed in the significant-safety-risk compounding category in 2023, later withdrawn by the nominators. Bremelanotide, its free-acid relative, is approved.46
AustraliaPrescription-only since 2018; enforcement against nasal sprays in 2023 to 2026.47
SportNot named on the 2026 WADA list. As an unapproved substance it falls under class S0, prohibited at all times.48
06

Open questions

  1. Whether switching on the pigment receptor itself promotes melanoma, or whether the reported cases reflect sunbeds, surveillance and prior risk. A 2020 mouse study found the opposite effect.16,29,40
  2. The true rate of harm, given that bought products contained 43% to 88% of the labelled amount with unknown impurities.17
  3. The cause of the vascular and kidney events: the drug's own action on the sympathetic system, contaminants, or other drugs taken with it.30,31
07

Common questions

What is Melanotan II?

A cyclic seven-residue copy of part of alpha-MSH, the hormone behind skin pigment, made at the University of Arizona in 1989. It acts on several melanocortin receptors.

Is Melanotan II the same as PT-141?

No, but close. PT-141 (bremelanotide) is the same ring with a free acid at the end instead of an amide. Bremelanotide went on to a US licence; Melanotan II did not.

Is Melanotan II legal in the UK?

It is an unlicensed medicine. Selling or advertising it for human use is illegal, and the MHRA has warned against it since 2008. It is sold here only as a research material.

What harms have been reported?

Changing moles, several melanoma reports, muscle breakdown with kidney injury, renal infarction, a brain syndrome and priapism, all in people using unlicensed products.

Is Melanotan II banned in sport?

It is not named on the 2026 WADA list, but as an unapproved substance it falls under class S0.

—

See also

PT-141 Entry 0018GHK-Cu Entry 0003Skin and copper Shelf
08

References

  1. Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J Med Chem. 1989;32(12):2555–2561. PMID 2555512
  2. Hadley ME. Discovery that a melanocortin regulates sexual functions in male and female humans. Peptides. 2005;26(10):1687–1689. PMID 15996790
  3. Hadley ME, et al. Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity. Pigment Cell Res. 1989;2(6):478–484. PMID 2557603
  4. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921–930. PMID 16412534
  5. King SH, et al. Melanocortin receptors, melanotropic peptides and penile erection. Curr Top Med Chem. 2007;7(11):1098–1106. PMID 17584130
  6. Langendonk JG, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48–59. PMID 26132941
  7. Ugwu SO, et al. A comparison of HPLC and bioassay methods for plasma melanotan-II determination: application to a pharmacokinetic study in rats. Biopharm Drug Dispos. 1994;15(5):383–390. PMID 7981427
  8. Lan EL, et al. Preformulation studies with melanotan-II: a potential skin cancer chemopreventive peptide. J Pharm Sci. 1994;83(8):1081–1084. PMID 7983590
  9. Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777–1784. PMID 8637402
  10. Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998;160(2):389–393. PMID 9679884
  11. Wessells H, et al. 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. PMID 11018622
  12. Langan EA, et al. Change in moles linked to use of unlicensed "sun tan jab". BMJ. 2009;338:b277. PMID 19174439
  13. Evans-Brown M, et al. Use of melanotan I and II in the general population. BMJ. 2009;338:b566. PMID 19224885
  14. Fan W, et al. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385(6612):165–168. PMID 8990120
  15. Wessells H, et al. MT-II induces penile erection via brain and spinal mechanisms. Ann N Y Acad Sci. 2003;994:90–95. PMID 12851302
  16. Wu JC, et al. Topical MTII therapy suppresses melanoma through PTEN upregulation and cyclooxygenase II inhibition. Int J Mol Sci. 2020;21(2):681. PMID 31968661
  17. Breindahl T, et al. Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet. Drug Test Anal. 2015;7(2):164–172. PMID 24771717
  18. Cousen P, Colver G, Helbling I. Eruptive melanocytic naevi following melanotan injection. Br J Dermatol. 2009;161(3):707–708. PMID 19575725
  19. Cardones AR, Grichnik JM. Alpha-melanocyte-stimulating hormone-induced eruptive nevi. Arch Dermatol. 2009;145(4):441–444. PMID 19380666
  20. Hueso-Gabriel L, et al. [Eruptive dysplastic nevi following melanotan use]. Actas Dermosifiliogr. 2012;103(4):329–331. PMID 22425244
  21. Mang R, Krahl D, Assmann T. [Dermoscopic changes in melanocytic nevi during use of melanotan II]. Hautarzt. 2012;63(11):880–884. PMID 23052015
  22. Sivyer GW. Changes of melanocytic lesions induced by Melanotan injections and sun bed use in a teenage patient with FAMMM syndrome. Dermatol Pract Concept. 2012;2(3):203a10. PMID 23785612
  23. Ferrándiz-Pulido C, et al. An eruptive pigmented lesion after melanotan injection. Clin Exp Dermatol. 2011;36(7):801–802. PMID 21933235
  24. Paurobally D, et al. Melanotan-associated melanoma. Br J Dermatol. 2011;164(6):1403–1405. PMID 21564053
  25. Ong S, Bowling J. Melanotan-associated melanoma in situ. Australas J Dermatol. 2012;53(4):301–302. PMID 22724573
  26. Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34–36. PMID 24355990
  27. Yassin Alsabbagh A, Bhujel N, Singh RP. Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma? Int J Oral Maxillofac Surg. 2025;54(9):806–808. PMID 40210573
  28. Vadner DJ, Smith S. Five primary melanomas in situ in a patient with recent tanning bed use, melanotan exposure, and anabolic hormone use. JAAD Case Rep. 2026;73:111–114. PMID 42328529
  29. Habbema L, et al. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017;56(10):975–980. PMID 28266027
  30. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol. 2012;50(10):1169–1173. PMID 23121206
  31. Peters B, et al. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020;9(2):159–161. PMID 31953620
  32. Kaski D, et al. Melanotan and the posterior reversible encephalopathy syndrome. Ann Intern Med. 2013;158(9):707–708. PMID 23648958
  33. Devlin J, Pomerleau A, Foote J. Melanotan II overdose associated with priapism. Clin Toxicol. 2013;51(4):383. PMID 23537392
  34. Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019;12(2):e227644. PMID 30796078
  35. Mallory CW, Lopategui DM, Cordon BH. Melanotan tanning injection: a rare cause of priapism. Sex Med. 2021;9(1):100298. PMID 33460908
  36. Bonchev A. Changes in oral mucosa associated with Melanotan II injections: a case report. Life. 2026;16(2):265. PMID 41752902
  37. Dickson D, Hlaing Htwe S. Pyoderma gangrenosum secondary to melanotan. Cureus. 2025;17(12):e98297. PMID 41487785
  38. Hope VD, et al. Injection site infections and injuries in men who inject image- and performance-enhancing drugs. Epidemiol Infect. 2015;143(1):132–140. PMID 24713416
  39. Langan EA, Nie Z, Rhodes LE. Melanotropic peptides: more than just "Barbie drugs" and "sun-tan jabs"? Br J Dermatol. 2010;163(3):451–455. PMID 20545686
  40. Böhm M, et al. An overview of benefits and risks of chronic melanocortin-1 receptor activation. J Eur Acad Dermatol Venereol. 2025;39(1):39–51. PMID 39082868
  41. Gilhooley E, Daly S, McKenna D. Melanotan II user experience: a qualitative study of online discussion forums. Dermatology. 2021;237(6):995–999. PMID 34464955
  42. Ryakhovsky VV, et al. The first preparative solution phase synthesis of melanotan II. Beilstein J Org Chem. 2008;4:39. PMID 19043625
  43. Kingsberg SA, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899–908. PMID 31599840
  44. PubChem. Melanotan II (CID 92432), bremelanotide (CID 9941379) and afamelanotide (CID 16197727), checked 2 Nov 2026.
  45. European Medicines Agency. Scenesse (afamelanotide): European public assessment report, authorised 22 December 2014. ema.europa.eu
  46. US Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A, lists of 29 September 2023 and 14 May 2026; and the page on bulk substances that may present significant safety risks. fda.gov
  47. Therapeutic Goods Administration (Australia). Final decisions, November 2017, item 1.7 Melanotan II (Schedule 4, in force 1 June 2018); enforcement page on tanning nasal sprays, 2023 to 2026. tga.gov.au
  48. World Anti-Doping Agency. The 2026 Prohibited List (in force 1 January 2026). wada-ama.org Class S0.
  49. Palatin Technologies. Press release on settlement with Competitive Technologies, 22 January 2008. sec.gov
  50. Press reports of regulator actions: HealthDay, 6 September 2007 (FDA warning letter); Pink Sheet, 24 November 2008 (MHRA warning of 17 November 2008); Cosmetics Business, 1 August 2011 (MHRA, Ubertan); CosmeticsDesign-Europe, 4 September 2013 (MHRA Yellow Card figures); ITV News, 16 May 2025 (Trading Standards, nasal sprays).

Peptidarium Library. Melanotan II (entry 0026), revision 1.0, 2 November 2026. peptidarium.com/library/melanotan-ii

09

Revision history

RevDateChangeBy
1.02 Nov 2026Entry created.[Scientific editor]

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