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Comparison

Melanotan I vs Melanotan II

Both are melanocortins, so the meaningful differences are in kinetics, evidence and regulatory status.

On published evidence alone, Melanotan I is the better documented of the two (regulator approved). That is a statement about the state of the literature, not a recommendation.

Melanotan I Melanotan II
Class Melanocortins Melanocortins
Evidence Regulator approved Preliminary human
Human trials ~12 ~6
Half-life ~1 hour (implant gives sustained release) ~1-2 hours
Reported range 500 mcg - 1 mg 250 mcg - 1 mg
Frequency Daily, or 16 mg implant every 2 months (approved use) Daily loading then 2-3x weekly maintenance
Routes Subcutaneous Subcutaneous
FDA approved Yes No
Research use only No Yes
Banned in sport No No
Studied for Erythropoietic protoporphyria, Photoprotection, Tanning Tanning, Appetite suppression, Erectile function
Reported side effects Nausea, Headache, Implant-site reactions, Darkening of existing naevi, Fatigue Nausea, Facial flushing, Spontaneous erections, Darkening of moles, Appetite loss, Lethargy

Melanotan I

Afamelanotide is a linear alpha-MSH analog with substitutions at positions 4 and 7 that increase potency and stability, and it is comparatively selective for the melanocortin-1 receptor. Selectivity means it stimulates eumelanin production without the MC4R-driven nausea and erectile effects of melanotan II. It is approved as a subcutaneous implant to increase pain-free light exposure in erythropoietic protoporphyria.

Melanotan II

Melanotan II is a cyclic lactam analog of alpha-melanocyte-stimulating hormone that activates melanocortin receptors non-selectively, including MC1R, MC3R and MC4R. MC1R activation drives melanogenesis and tanning; MC4R activation produces the appetite suppression and the erectile effects that led to the development of the selective derivative bremelanotide. Non-selectivity is precisely the problem: users cannot obtain one effect without the others, and health agencies in several countries have issued warnings about unregulated supply and about melanoma risk from darkening existing naevi.

Melanotan I vs Melanotan II: common questions

What is the difference between Melanotan I and Melanotan II?

Both are melanocortins. Melanotan I: A selective MC1R agonist, FDA approved as an implant for a rare photosensitivity disorder. Melanotan II: A non-selective melanocortin agonist that causes tanning, appetite suppression and erections. Subject of repeated regulatory warnings.

Which has stronger evidence, Melanotan I or Melanotan II?

Melanotan I has the stronger evidence base (regulator approved, about 12 human studies) compared with Melanotan II (preliminary human).

Are Melanotan I and Melanotan II FDA approved?

Only Melanotan I is FDA approved (Increase of pain-free light exposure in adults with erythropoietic protoporphyria (Scenesse)). Melanotan II is not approved for any indication.

References

Regulatory and primary sources

  1. PubChem compound record (CID 16197727) ↗ · structure, identifiers, synonyms
  2. DailyMed: FDA-approved labeling for Melanotan I ↗ · indications, dosing, warnings as approved
  3. FDA Drugs@FDA database ↗ · approval history
  4. CAS Registry Number 75921-69-6 ↗ · chemical identity
  5. PubChem compound record (CID 92432) ↗ · structure, identifiers, synonyms
  6. FDA: Unapproved drugs and "research use only" products ↗ · regulatory status of non-approved products
  7. CAS Registry Number 121062-08-6 ↗ · chemical identity

Published literature

  1. Perez-Bootello J, Cova-Martin R, Naharro-Rodriguez J, et al.. Vitiligo: Pathogenesis and New and Emerging Treatments.Int J Mol Sci 2023.PubMed 38139134 · doi:10.3390/ijms242417306
  2. Bayerl C. [Undesirable pigmentation].Hautarzt 2015.PubMed 26315100 · doi:10.1007/s00105-015-3671-4
  3. Cong TX, Hao D, Wen X, et al.. From pathogenesis of acne vulgaris to anti-acne agents.Arch Dermatol Res 2019.PubMed 30859308 · doi:10.1007/s00403-019-01908-x
  4. Stölzel U, Kubisch I, Stauch T. [Porphyrias-what is verified?].Internist (Berl) 2018.PubMed 30328490 · doi:10.1007/s00108-018-0509-z
  5. Zubair R, Hamzavi IH. Phototherapy for Vitiligo.Dermatol Clin 2020.PubMed 31753192 · doi:10.1016/j.det.2019.08.005
  6. Sweeney P, Gimenez LE, Hernandez CC, et al.. Targeting the central melanocortin system for the treatment of metabolic disorders.Nat Rev Endocrinol 2023.PubMed 37365323 · doi:10.1038/s41574-023-00855-y
  7. Minder EI, Schneider-Yin X. Afamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.Expert Rev Clin Pharmacol 2015.PubMed 25470471 · doi:10.1586/17512433.2014.956089
  8. Wu J, Cotliar R. Afamelanotide: An Orphan Drug with Potential for Broad Dermatologic Applications.J Drugs Dermatol 2021.PubMed 33683075 · doi:10.36849/JDD.5526
  9. Janvier S, De Spiegeleer B, Vanhee C, et al.. Falsification of biotechnology drugs: current dangers and/or future disasters?.J Pharm Biomed Anal 2018.PubMed 30165334 · doi:10.1016/j.jpba.2018.08.037
  10. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.Peptides 2006.PubMed 16412534 · doi:10.1016/j.peptides.2005.01.029
  11. Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue.Int J Obes (Lond) 2010.PubMed 20935665 · doi:10.1038/ijo.2010.182
  12. Wessells H, Levine N, Hadley ME, et al.. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.Int J Impot Res 2000.PubMed 11035391 · doi:10.1038/sj.ijir.3900582
  13. 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.PubMed 31953620 · doi:10.1007/s13730-020-00447-z
  14. Allard J, Giuliano F. Central nervous system agents in the treatment of erectile dysfunction: how do they work?.Curr Urol Rep 2001.PubMed 12084236 · doi:10.1007/s11934-001-0044-6
  15. 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.PubMed 8637402 · doi:10.1016/0024-3205(96)00160-9
  16. Hadley ME. Discovery that a melanocortin regulates sexual functions in male and female humans.Peptides 2005.PubMed 15996790 · doi:10.1016/j.peptides.2005.01.023

Literature retrieved from PubMed on October 16, 2026, favouring human studies and reviews. Numbered markers in the text show which paper supports which statement; uncited entries are background reading.

Read this first This page compares published reference data. It is not medical advice and not a recommendation to use either compound. Several compounds documented on this site are not approved for human use.