Liquid syntax error (snippets/seo-jsonld line 46): Variable '{{ shop.url | append: routes.search_url | append: '?q={search_term_string}' was not properly terminated with regexp: /\}\}/ Skip to content

Free Express shipping over $300 · Ships from CanadaFree Express over $300

Horizon® Peptides

MelanocortinJournal

Melanocortin peptides: one hormone, five receptors, four analogues

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a hormone of 13 amino acids, one of a family of peptides that act on cells through five melanocortin receptors.12 This article covers four related peptides: afamelanotide (Melanotan I), Melanotan II, bremelanotide (PT-141) and the fragment KPV. Two are the active ingredients of licensed medicines, one is known from three small studies in men and from case reports of harm, and for one the FDA has identified no human exposure data.3456789

  • Horizon Peptides editorial
  • Updated
  • 8 min read
  • 36 sources

Evidence cited on this page

  • 1 cell study
  • 1 animal study
  • 6 human studies
  • 6 reviews
  • 2 chemistry studies
  • 20 other sources
On this page7 sections

Key points

  • Review Peptides derived from the proopiomelanocortin gene, alpha-MSH among them, act on five receptors with different patterns of tissue expression.210
  • Human study Afamelanotide and bremelanotide have each been tested in randomized, placebo-controlled trials and are licensed for narrow indications.11121314
  • Human study The Melanotan II studies cited here enrolled 3, 10 and 10 men, and case reports describe serious harm after use of unregulated products.567815
  • Animal study In mice with peritonitis, KPV reduced the build-up of white blood cells without behaving like a melanocortin receptor agonist.16
  • Health Canada lists Melanotan I, Melanotan II and KPV among unauthorized peptide drugs it has seized.17

Alpha-MSH and its receptors

Chemistry study In peptide notation alpha-MSH is written Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2: thirteen residues, with an acetyl cap on one end and an amide on the other.1

Review The melanocortin peptides derive from the proopiomelanocortin gene, and alpha-MSH, beta-MSH, gamma-MSH and adrenocorticotropic hormone (ACTH) are the known natural activators of the receptors.210 The receptors cross the cell membrane seven times, are coupled to G proteins and signal through cyclic AMP, a messenger inside the cell.10 Each subtype has its own pattern of tissue expression and its own ranking of the natural peptides by potency.10

Two classes of G protein-coupled receptor that research peptides are studied at A receptor drawn crossing the cell membrane seven times. A peptide binds it outside the cell; inside, a G protein passes the signal on. Two classes of this kind of receptor are listed. Class B, the secretin family: the GLP-1, GIP and glucagon receptors and the GHRH receptor. Class A, the rhodopsin family: the ghrelin receptor and the five melanocortin receptors, MC1R to MC5R. Peptide Outside the cell Inside the cell G protein signal A receptor of this kind crosses the membrane seven times. Two of its classes: Class B secretin family GLP-1, GIP and glucagon receptors GHRH receptor Class A rhodopsin family Ghrelin receptor Melanocortin receptors MC1R to MC5R
Melanocortin receptors belong to the seven-transmembrane receptors
Receptor What the cited sources say
MC1R Expressed in skin, on pigment cells called melanocytes; gene variants are associated with red hair1418
MC2R Carries the action of ACTH on glucocorticoid production in the adrenal gland18
MC3R Involved in metabolic regulation; gene variants are associated with severe childhood obesity18
MC4R As for MC3R; found on neurons in many areas of the central nervous system1418
MC5R Function “remains to be fully elucidated”18

The four analogues

Analogue Also called Shape Formula and weight Licensed medicine
Afamelanotide Melanotan I, NDP-MSH Linear, 13 residues C78H111N21O19, 1646.8 g/mol19 Scenesse13
Melanotan II MT-II Cyclic, 7 residues, amide end C50H69N15O9, 1024.2 g/mol20 None found21
Bremelanotide PT-141 The same ring, free acid end C50H68N14O10, 1025.2 g/mol22 Vyleesi14
KPV Alpha-MSH(11-13) Linear, 3 residues C16H30N4O4, 342.43 g/mol23 None found21

Afamelanotide (Melanotan I)

Cell study In 1980 chemists replaced the methionine at position 4 of alpha-MSH with norleucine, and the phenylalanine at position 7 with its mirror-image D form.24 The analogue resisted breakdown by serum enzymes, showed prolonged activity on frog skin, and was 26 times as potent as alpha-MSH in a mouse melanoma adenylate cyclase assay.24 This molecule is afamelanotide, which its labels describe as binding predominantly to MC1R.131925

Melanotan II

Cell study In 1989 a team that included two of the same authors closed part of the chain into a ring by joining the side chains of two residues.1 The seven-residue version bridged between aspartic acid and lysine, later named Melanotan II, was 90 times as potent as alpha-MSH in a lizard skin assay; in frog skin the analogues were much less potent.15

Bremelanotide (PT-141)

Review A 2006 history by two researchers who had studied Melanotan II describes PT-141 as a new analogue of Melanotan II.526 Its label says that it activates several receptor subtypes non-selectively, MC1R and MC4R most potently, and that how it acts in the licensed indication is unknown.14

KPV

Animal study KPV is lysine-proline-valine, the last three residues of alpha-MSH, and it lacks His-Phe-Arg-Trp, which one paper calls the core melanocortin peptide.116 In mice with peritonitis it reduced the build-up of white blood cells, a blocker of MC3R and MC4R did not stop the effect, and the authors concluded that it is unlikely to act through melanocortin receptors.16

Human evidence

  • Human study Afamelanotide. Two randomized, double-blind trials, funded by the manufacturer and others, enrolled 168 people with erythropoietic protoporphyria, a condition in which light causes severe pain.1113 Those given afamelanotide implants recorded more hours in direct sunlight without pain than those given placebo, and adverse events were mostly mild.11
  • Human study Bremelanotide. Two identical phase 3 trials, funded by its two sponsoring companies, randomized 1,267 premenopausal women with hypoactive sexual desire disorder.12 Scores on two questionnaire measures moved by a fraction of a point more than with placebo, a statistically significant difference, and nausea, flushing and headache were more common.12
  • Review Bremelanotide. A 2024 critical review judged the effects statistically modest, questioned the validity of the measures, and found that results for 8 of the 11 registered efficacy outcomes had not been published before.27
  • Human study Melanotan II. A single-blind pilot study compared it with saline in three healthy men.5 It recorded mild nausea at most levels tested, grade II sleepiness and fatigue in one man at the highest level, spontaneous erections, and darker skin in two men a week later.5 Two double-blind, placebo-controlled crossover studies, each in ten men with erectile dysfunction, recorded longer erections after Melanotan II than after placebo.67 Nausea, stretching and yawning were more frequent, and in the second study severe nausea followed 4 of the 19 times it was given.67
  • KPV. The FDA states that it has identified no human exposure data for KPV, and searches of ClinicalTrials.gov returned no study of it.928

Unregulated melanotan products

Review Products labelled Melanotan I or Melanotan II are sold without authorization for tanning, in forms that include nasal sprays.829

  • Review A 2017 review found growing numbers of case reports of changes in existing moles and of new, atypical moles, and four reports of melanoma arising in existing moles during or shortly after use; it adds that conclusive evidence of a link is lacking.8
  • Human study A 2012 case report describes a 39-year-old man seen in an emergency department two hours after using Melanotan II bought online, by his account several times the suggested starting amount.15 He had a racing heart, sweating, tremor and anxiety, then rhabdomyolysis (a breakdown of muscle) with kidney dysfunction; mass spectrometry confirmed the substance.15
  • Chemistry study Vials of Melanotan II bought from three online shops and analysed by liquid chromatography and mass spectrometry held between 43% and 88% of the amount each shop claimed, and vials from two shops contained 4.1% to 5.9% of unidentified impurities.30

Three regulators have published warnings.

  • Health Canada’s advisory of 9 April 2026 names Melanotan I and II and KPV among seized unauthorized peptide drugs.17 It says that such products have not been assessed for safety, efficacy and quality, and that a “For Research Use Only” label does not exempt a product from regulatory requirements.17
  • The FDA notes published case reports of serious adverse events with Melanotan II, among them melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.9
  • Australia’s TGA reported in August 2026 that five seized nasal spray bottles of one product held from about three quarters to almost double the labelled amount.31

Regulatory status

Statements were checked against each authority’s own page on 8 October 2026.

  • Afamelanotide. The European Medicines Agency lists Scenesse as authorized since 22 December 2014, under exceptional circumstances, for prevention of phototoxicity in adults with erythropoietic protoporphyria.32 The FDA approved it on 8 October 2019 to increase pain-free light exposure in adults with a history of phototoxic reactions from that condition.313 Health Canada authorized it for the same use on 9 July 2026; its Drug Product Database shows the status “Approved”, defined there as authorized but not yet marketed in Canada.253334 Both labels recommend regular full-body skin examinations, because existing moles and freckles may darken.1325
  • Bremelanotide. The FDA approved Vyleesi on 21 June 2019 for premenopausal women with acquired, generalized hypoactive sexual desire disorder.414 The label warns of nausea (40% of patients in the phase 3 trials), a short-lived rise in blood pressure and patches of darker skin.14 Health Canada’s database and the EMA’s table of centrally authorized medicines hold no bremelanotide product.3536
  • Melanotan II and KPV. Neither name returned a product in Health Canada’s database or in the FDA’s approved-drug data.2135

An approval covers one manufactured medicine for one indication, not the same molecule supplied as a research material, which Horizon sells for laboratory research use only. The guide to evidence levels in peptide research sets out how to weigh cell, animal and human findings.

Frequently asked questions

Is Melanotan I the same molecule as afamelanotide?

PubChem lists Melanotan I as a synonym of afamelanotide.19 The licensed medicine is a manufactured implant, not a research material.13

How do Melanotan II and PT-141 differ?

They share one ring; Melanotan II ends in an amide and bremelanotide in a free acid, so their formulas differ by one nitrogen, one hydrogen and one oxygen.2022

Which melanocortin receptor is linked to pigmentation?

MC1R, which a review places in skin and a drug label on pigment cells.1418

Is any of these compounds authorized in Canada?

Afamelanotide is, as the prescription implant Scenesse, shown on 8 October 2026 as approved but not yet marketed.3334 Searches for bremelanotide, melanotan and KPV returned no product.35

References

Every record links to its PubMed entry or its source. The label under each one names the kind of work it is.

  1. Al-Obeidi F, Castrucci AM, Hadley ME, et al. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J Med Chem. 1989.

    Chemistry studyDesign and synthesis of cyclic lactam analogues, tested in frog and lizard skin bioassays

    PubMed 2555512 (opens in a new tab)abcde

  2. Gantz I, Fong TM. The melanocortin system. Am J Physiol Endocrinol Metab. 2003.

    ReviewNarrative review of the melanocortin system

    PubMed 12556347 (opens in a new tab)abc

  3. U.S. Food and Drug Administration. Drugs@FDA: New Drug Application 210797, Scenesse (afamelanotide) implant, original approval 8 October 2019. Accessed 8 October 2026.

    Source

    accessdata.fda.gov (opens in a new tab)ab

  4. U.S. Food and Drug Administration. Drugs@FDA: New Drug Application 210557, Vyleesi (bremelanotide acetate), original approval 21 June 2019. Accessed 8 October 2026.

    Source

    accessdata.fda.gov (opens in a new tab)ab

  5. 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.

    Human studySingle-blind, placebo-controlled pilot phase 1 study in three healthy male volunteers

    PubMed 8637402 (opens in a new tab)abcdefg

  6. 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.

    Human studyDouble-blind, placebo-controlled crossover study in ten men with erectile dysfunction of no known organic cause

    PubMed 9679884 (opens in a new tab)abcde

  7. Wessells H, Gralnek D, Dorr R, et al. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000.

    Human studyDouble-blind, placebo-controlled crossover study in ten men with erectile dysfunction and organic risk factors

    PubMed 11018622 (opens in a new tab)abcde

  8. Habbema L, Halk AB, Neumann M, et al. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017.

    ReviewNarrative review of case reports and safety literature

    PubMed 28266027 (opens in a new tab)abcde

  9. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 22 April 2026; Melanotan II and KPV listed among substances nominated but withdrawn). Accessed 8 October 2026.

    Source

    fda.gov (opens in a new tab)abc

  10. Yang Y. Structure, function and regulation of the melanocortin receptors. Eur J Pharmacol. 2011.

    ReviewReview of receptor structure and pharmacology, including the author's chimeric and mutated receptor studies

    PubMed 21208602 (opens in a new tab)abcd

  11. Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015.

    Human studyTwo multicentre, randomized, double-blind, placebo-controlled trials in 168 patients with erythropoietic protoporphyria (74 in the European Union, 94 in the United States)

    PubMed 26132941 (opens in a new tab)abcd

  12. Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019.

    Human studyTwo identical phase 3, randomized, double-blind, placebo-controlled trials (RECONNECT) in 1,267 premenopausal women with hypoactive sexual desire disorder

    PubMed 31599840 (opens in a new tab)abcd

  13. U.S. Food and Drug Administration label, published on DailyMed by the U.S. National Library of Medicine. SCENESSE (afamelanotide) implant, prescribing information (sections revised August 2024; label version published 13 May 2026). Accessed 8 October 2026.

    Source

    dailymed.nlm.nih.gov (opens in a new tab)abcdefg

  14. U.S. Food and Drug Administration label, published on DailyMed by the U.S. National Library of Medicine. VYLEESI (bremelanotide) prescribing information (revised March 2024; label version published 18 November 2025). Accessed 8 October 2026.

    Source

    dailymed.nlm.nih.gov (opens in a new tab)abcdefgh

  15. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012.

    Human studySingle case report from a poison control centre

    PubMed 23121206 (opens in a new tab)abc

  16. Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003.

    Animal studyMouse models of crystal-induced and interleukin-1beta-induced peritonitis, with macrophage experiments in vitro

    PubMed 12750433 (opens in a new tab)abcd

  17. Health Canada. Think twice before injecting peptides bought online: unauthorized products can seriously harm you (public advisory RA-81874, published 9 April 2026). Accessed 8 October 2026.

    Source

    recalls-rappels.canada.ca (opens in a new tab)abc

  18. Novoselova TV, Chan LF, Clark AJL. Pathophysiology of melanocortin receptors and their accessory proteins. Best Pract Res Clin Endocrinol Metab. 2018.

    ReviewNarrative review of receptor genetics and physiology

    PubMed 29678289 (opens in a new tab)abcdef

  19. PubChem, U.S. National Library of Medicine. Afamelanotide, PubChem compound record CID 16197727 (formula, molecular weight and synonyms including Melanotan I, NDP-MSH and (Nle(4),D-Phe(7))alpha-MSH). Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)abc

  20. PubChem, U.S. National Library of Medicine. Melanotan II, PubChem compound record CID 92432 (formula, molecular weight and the structure Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2). Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)ab

  21. U.S. Food and Drug Administration. Drugs@FDA data, openFDA drugsfda endpoint (searches for melanotan, KPV and lys-pro-val as ingredient, generic, substance and brand name; no matches). Accessed 8 October 2026.

    Source

    open.fda.gov (opens in a new tab)abc

  22. PubChem, U.S. National Library of Medicine. Bremelanotide, PubChem compound record CID 9941379 (formula, molecular weight and synonyms including PT-141). Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)ab

  23. PubChem, U.S. National Library of Medicine. Msh (11-13) (L-lysyl-L-prolyl-L-valine), PubChem compound record CID 125672. Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)↑

  24. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci U S A. 1980.

    Cell studyFrog skin bioassay, mouse melanoma adenylate cyclase and tyrosinase assays, and incubation with serum enzymes

    PubMed 6777774 (opens in a new tab)ab

  25. Clinuvel, Inc., published in Health Canada's Drug Product Database. SCENESSE (afamelanotide) product monograph including patient medication information; date of initial authorization 9 July 2026. Accessed 8 October 2026.

    Source

    pdf.hres.ca (opens in a new tab)abc

  26. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006.

    ReviewHistorical review by two researchers involved in the analogues' development

    PubMed 16412534 (opens in a new tab)↑

  27. Spielmans GI, Ellefson EM. Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder. J Sex Res. 2024.

    ReviewCritical review and reanalysis of the phase 3 RECONNECT trial outcomes

    PubMed 36809187 (opens in a new tab)ab

  28. ClinicalTrials.gov, U.S. National Library of Medicine. ClinicalTrials.gov searches for KPV as a search term and as an intervention, and for Lys-Pro-Val as a search term (no studies returned). Accessed 8 October 2026.

    Source

    clinicaltrials.gov (opens in a new tab)↑

  29. Therapeutic Goods Administration, Australian Government. Don't risk using tanning products containing melanotan (published 24 January 2025). Accessed 8 October 2026.

    Source

    tga.gov.au (opens in a new tab)↑

  30. Breindahl T, Evans-Brown M, Hindersson P, 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.

    Chemistry studyLC-UV and tandem mass spectrometry analysis of vials bought from three online shops

    PubMed 24771717 (opens in a new tab)↑

  31. Therapeutic Goods Administration, Australian Government. Melanotan II tanning peptide products found to be inconsistently dosed (safety advisory, published 17 August 2026). Accessed 8 October 2026.

    Source

    tga.gov.au (opens in a new tab)↑

  32. European Medicines Agency. Scenesse (afamelanotide): European public assessment report overview (marketing authorisation issued 22 December 2014, under exceptional circumstances). Accessed 8 October 2026.

    Source

    ema.europa.eu (opens in a new tab)↑

  33. Health Canada. Drug Product Database: SCENESSE, DIN 02569825, afamelanotide (as afamelanotide acetate) implant; current status Approved, status date 9 July 2026. Accessed 8 October 2026.

    Source

    health-products.canada.ca (opens in a new tab)ab

  34. Health Canada. Drug Product Database: terminology (drug statuses; "Approved" refers to a product authorized for sale in Canada that has not yet been marketed in Canada). Accessed 8 October 2026.

    Source

    canada.ca (opens in a new tab)ab

  35. Health Canada. Drug Product Database: active ingredient searches for bremelanotide, melanotan, KPV, lys-pro-val and lysyl, run through the database's public API (no products returned). Accessed 8 October 2026.

    Source

    health-products.canada.ca (opens in a new tab)abc

  36. European Medicines Agency. Medicines data table of centrally authorised medicines, download dated 8 October 2026 (Scenesse listed; no entry containing bremelanotide or melanotan). Accessed 8 October 2026.

    Source

    ema.europa.eu (opens in a new tab)↑

Written by Horizon Peptides editorial. Checked against its sources on .

Related reading

The Journal

For laboratory research

Related products

Supplied for research use only. Nothing on this page is guidance on use.