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Melanotan 1 vs Melanotan 2

A Afamelanotide Melanocortin-1 receptor agonist; raises eumelanin without UV exposure FDA-approved (Scenesse implant) · Prescription C Melanotan II Non-selective melanocortin-receptor agonist; pigmentation via MC1R Not FDA-approved · FDA compounding nomination withdrawn

Residue Editorial Team · updated

In brief

Both are synthetic α-MSH analogs, but only one became a medicine. Afamelanotide (Melanotan I) is a melanocortin-1 receptor agonist approved as the Scenesse implant for erythropoietic protoporphyria1PubMedAfamelanotide: A Review in Erythropoietic Protoporphyria. Kim ES & Garnock-Jones KP Am J Clin Dermatol. 2016.,2FDADrugs@FDA: SCENESSE (NDA210797). CLIVUNEL INC; original approval 2019-10-08; Prescription.. Melanotan II is a shorter cyclic analog that also caused erections in small 1990s studies and was never approved3PubMedEvaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Dorr RT et al. Life Sci. 1996.,4PubMedSynthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. Wessells H et al. J Urol. 1998.; FDA records case reports of melanoma5FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..

How do Afamelanotide and Melanotan II compare at a glance?

Table 1. Afamelanotide and Melanotan II on the dimensions that matter most; every entry is cited.
DimensionAfamelanotideMelanotan II
Structure13-residue α-MSH analog6PubChemPubChem compound record: Afamelanotide. C78H111N21O19 · MW 1646.8 g/mol.Cyclic, lactam-bridged α-MSH(4-10) analog3
Receptor profileMelanocortin-1 receptor agonist1Non-selective melanocortin-receptor agonist7PubMedMelanotan II: a possible cause of renal infarction: review of the literature and case report. Peters B et al. CEN Case Rep. 2020.
Effects in humansPigmentation; light tolerance in EPP8PubMedPharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Minder EI et al. Clin Pharmacokinet. 2017.,9PubMedAfamelanotide for Erythropoietic Protoporphyria. Langendonk JG et al. N Engl J Med. 2015.Pigmentation, erections, nausea, yawning3,4
Largest trialTwo RCTs, 168 patients with EPP910-man placebo-controlled crossover studies4,10PubMedEffect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Wessells H et al. Urology. 2000.
How it is given16 mg SC implant every 60 days in trials9SC injection, 0.025 mg/kg in trials4
Reported harmsHeadache, nausea, implant-site reactions1,11PubMedAfamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Wensink D et al. Expert Rev Clin Pharmacol. 2021.Case reports: melanoma, rhabdomyolysis, priapism12PubMedMelanoma associated with the use of melanotan-II. Hjuler KF & Lorentzen HF Dermatology. 2014.,13PubMedMelanotan II injection resulting in systemic toxicity and rhabdomyolysis. Nelson ME et al. Clin Toxicol (Phila). 2012.,14PubMedMelanotan Tanning Injection: A Rare Cause of Priapism. Mallory CW et al. Sex Med. 2021.
FDAApproved: Scenesse, 20192Not approved; withdrawn compounding nomination5
Evidence gradeAC

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check,

First published

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Registry data · How we grade · Markdown + sources

Figure 1. Size of the research record, from PubMed and ClinicalTrials.gov at the data edition. Bars are scaled to the larger value in each row; volume is not quality.
PubMed records 121 625
Trial publications 12 5
Registered studies 23 1
Phase 3 studies 6 0

Afamelanotide Melanotan II

Both mimic α-melanocyte-stimulating hormone. Afamelanotide was the first α-MSH analog given to people, chosen for higher activity and stability than the natural hormone8. Melanotan II, Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 α-MSH(4-10)-NH2, is a shorter, ring-closed version with superpotent melanotropic activity in vitro3.

What is the evidence for afamelanotide?

Two randomized, double-blind, placebo-controlled trials in erythropoietic protoporphyria (74 and 94 patients) found that a 16 mg implant every 60 days increased pain-free time in direct sunlight and improved quality of life9. It is approved in the US as Scenesse2.

What is the evidence for Melanotan II?

A three-man pilot in 1996 showed tanning after five low doses and spontaneous erections3. Two ten-man crossover studies then showed it initiated erections in men with psychogenic or organic erectile dysfunction4,10. Since then the literature is mainly case reports of harm after unsupervised use12,13,7,14.

How should this evidence be read?

The two compounds are not interchangeable. Afamelanotide's grade A applies only to its approved use in EPP; its tanning effect in volunteers is a separate, smaller body of evidence8. Melanotan II has no approval for any use, and products sold under either name online are not the approved drug15PubMedRisks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Habbema L et al. Int J Dermatol. 2017..

Two identical glass beakers, one holding pale amber liquid and one clear, standing either side of a brass balance

Why do they get these evidence grades?

A Afamelanotide
FDA-approved (Scenesse, NDA 210797) for erythropoietic protoporphyria on the basis of randomized, placebo-controlled trials. Other uses are graded separately. Grade A: Approved / regulatory-grade.
C Melanotan II
Two double-blind, placebo-controlled crossover studies of 10 men each and a 3-man phase I pilot; the abstracts do not report randomization. Later literature is mainly case reports. Grade C: Limited / early human data.

Questions readers ask

What is the difference between Melanotan 1 and Melanotan 2?

Melanotan I (afamelanotide) is selective for the melanocortin-1 receptor and approved for EPP1,2. Melanotan II is non-selective, also produces erections, and is not approved7,4.

Which is safer, Melanotan 1 or Melanotan 2?

Only afamelanotide has a regulated product and long-term safety follow-up, with mostly mild adverse events8,1. Melanotan II's safety data are a few small studies plus case reports of serious harm12,13. A 2017 review warns that unregulated melanotan I and II products both carry risks, including changes in moles15.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 PubMed Kim ES, Garnock-Jones KP. Afamelanotide: A Review in Erythropoietic Protoporphyria. Am J Clin Dermatol 2016. PMID 26979527; doi:10.1007/s40257-016-0184-6.
  2. 2 FDA Drugs@FDA: SCENESSE (NDA210797). CLIVUNEL INC; original approval 2019-10-08; Prescription.
  3. 3 PubMed 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. PMID 8637402; doi:10.1016/0024-3205(96)00160-9.
  4. 4 PubMed 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. PMID 9679884.
  5. 5 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
  6. 6 PubChem PubChem compound record: Afamelanotide. C78H111N21O19 · MW 1646.8 g/mol.
  7. 7 PubMed Peters B, Hadimeri H, Wahlberg R, et al. 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.
  8. 8 PubMed Minder EI, Barman-Aksoezen J, Schneider-Yin X. Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Clin Pharmacokinet 2017. PMID 28063031; doi:10.1007/s40262-016-0501-5.
  9. 9 PubMed Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med 2015. PMID 26132941; doi:10.1056/NEJMoa1411481.
  10. 10 PubMed 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. PMID 11018622; doi:10.1016/s0090-4295(00)00680-4.
  11. 11 PubMed Wensink D, Wagenmakers MAEM, Langendonk JG. Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Expert Rev Clin Pharmacol 2021. PMID 33507118; doi:10.1080/17512433.2021.1879638.
  12. 12 PubMed Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology 2014. PMID 24355990; doi:10.1159/000356389.
  13. 13 PubMed 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.
  14. 14 PubMed Mallory CW, Lopategui DM, Cordon BH. Melanotan Tanning Injection: A Rare Cause of Priapism. Sex Med 2021. PMID 33460908; doi:10.1016/j.esxm.2020.100298.
  15. 15 PubMed Habbema L, Halk AB, Neumann M, et al. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol 2017. PMID 28266027; doi:10.1111/ijd.13585.