Home Compounds Sexual Health & Hormonal Melanotan-I (afamelanotide)
Sexual Health & Hormonal Research High Evidence

Melanotan-I (afamelanotide)

Linear melanocortin MC1R agonist (parent to MT-II). FDA-approved (Scenesse) for erythropoietic protoporphyria (EPP). Studied for photoprotection, tanning, and skin disorder research. Lacks the sexual side effects of MT-II.

melanocortinMC1RtanningphotoprotectionEPPScenesseafamelanotide
Half-life
90 minutes SC; implant (Scenesse) provides sustained release for 60 days
SKUs
1
Evidence
High Evidence

Melanotan I (afamelanotide) is a synthetic analog of alpha-MSH (alpha-melanocyte-stimulating hormone) that stimulates melanin production in the skin. It has been developed specifically for the treatment of erythropoietic protoporphyria (EPP), a rare photosensitivity disorder, and is approved in Europe for this indication under the name Scenesse. It has also been studied for other photoprotection purposes.

Erythropoietic Protoporphyria Treatment
EPP is a rare genetic disorder where exposure to sunlight or artificial light causes severe pain due to porphyrin accumulation. Afamelanotide was studied in randomized controlled trials in EPP patients and showed significant increases in pain-free light exposure time. It is approved in Europe and Australia for EPP and has FDA approval (Scenesse) in the US for this indication.
Photoprotection Research
Beyond EPP, researchers have studied whether afamelanotide could provide photoprotection to people with fair skin or other photosensitivity conditions. The induced melanin provides some protection against UV-induced DNA damage.
Other Photosensitivity Conditions
Research has also examined afamelanotide for conditions like polymorphic light eruption and solar urticaria, where abnormal skin reactions to light cause distress.
  • FDA and EMA approved for erythropoietic protoporphyria under the name Scenesse.
  • Randomized trials showed significant increases in pain-free sun exposure in EPP patients.
  • Induces melanin production through MC1R activation, resulting in skin darkening.
  • Well-tolerated in clinical trials for the approved EPP indication.

Melanotan I (afamelanotide) is distinct from Melanotan II, which is not approved for any use. The FDA-approved indication is specific to EPP, a rare condition. Use for general tanning or photoprotection in people without photosensitivity disorders is off-label and not supported by strong evidence. Melanotan II, a related but different compound with additional effects, should not be confused with Melanotan I.

When sunlight hits your skin, UV rays stimulate cells called melanocytes to produce melanin — the pigment that causes tanning. This process is driven by alpha-MSH, a hormone that activates the MC1R receptor on melanocytes. Melanotan I is a modified, longer-lasting version of alpha-MSH. Delivered as an implant that slowly releases under the skin, it continuously activates MC1R, causing melanocytes to produce more melanin over time. The induced melanin darkens the skin and provides some actual UV protection. In EPP patients, this protective melanin is particularly valuable because their condition makes even brief light exposure extremely painful.

Afamelanotide (Melanotan I as Scenesse) is FDA-approved for EPP with a characterized safety profile. Side effects include nausea, headache, fatigue, and injection site reactions from the implant. Skin darkening with nevi (mole) changes should be monitored. It is prescription-only and used under medical supervision for its approved indication. The unapproved analog Melanotan II is associated with more significant safety concerns and should be distinguished from Melanotan I.

High Evidence

This compound has been studied in multiple large randomized controlled trials with human subjects. The evidence base is strong and consistent across independent research groups.

Published Research Ranges
16mg subcutaneous implant for EPP (approved); 0.16mg/day equivalent; research doses lower
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.

Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.

Afamelanotide (Melanotan-I/Scenesse) for Erythropoietic Protoporphyria: Pivotal Trial
Lancet • 2015  • DOI: 10.1016/S0140-6736(14)61943-2
View Source
Afamelanotide (Scenesse) — FDA-Approved for Erythropoietic Protoporphyria
Drugs • 2020  • DOI: 10.1007/s40265-020-01301-3
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MC1R Agonism and Photoprotection: Afamelanotide in Skin Research
Journal of Investigative Dermatology • 2011  • DOI: 10.1038/jid.2011.53
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Afamelanotide for Erythropoietic Protoporphyria
 • 2015  • DOI: 10.1056/nejmoa1411481
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A feasibility and safety study of afamelanotide in acute stroke patients - an open label, proof of concept, phase iia clinical trial
 • 2023  • DOI: 10.1186/s12883-023-03338-9
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Evaluation of the immunogenicity of the synthetic α-melanocyte-stimulating hormone (α-MSH) analogue afamelanotide ([Nle4-D-Phe7]-α-MSH, Scenesse®) in erythropoietic protoporphyria patients by ELISA detecting both anti-afamelanotide and anti-α-MSH antibodies
 • 2015  • DOI: 10.1159/000362174
View Source
Opportunities to improve the adoption of health-related quality of life evidence as part of the French Health Technology Assessment process
 • 2023  • DOI: 10.1186/s12961-023-01081-8
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Topical treatment strategies to manipulate human skin pigmentation
 • 2020  • DOI: 10.1016/j.addr.2020.02.002
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Insights into Tanning Biology and Tanning Products
 • 2026
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An overview of benefits and risks of chronic melanocortin-1 receptor activation
 • 2025  • DOI: 10.1111/jdv.20269
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Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases
 • 2025  • DOI: 10.3390/diseases13090305
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Journey through the spectacular landscape of melanocortin 1 receptor
 • 2024  • DOI: 10.1111/pcmr.13180
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Porous silicon and silica carriers for delivery of peptide therapeutics
 • 2024  • DOI: 10.1007/s13346-024-01609-7
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Afamelanotide in protoporphyria and other skin diseases: a review
 • 2024  • DOI: 10.5114/ada.2024.138818
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Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria
 • 2023  • DOI: 10.3390/ph17010031
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Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria
 • 2022  • DOI: 10.3390/diagnostics12010151
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The genetics of obesity: from discovery to biology
 • 2022  • DOI: 10.1038/s41576-021-00414-z
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Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma
 • 2022  • DOI: 10.1016/j.apsb.2021.09.019
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Visible light. Part I: Properties and cutaneous effects of visible light
 • 2021  • DOI: 10.1016/j.jaad.2021.02.048
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Porphyrias in the Age of Targeted Therapies
 • 2021  • DOI: 10.3390/diagnostics11101795
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2019 FDA TIDES (Peptides and Oligonucleotides) Harvest
 • 2020  • DOI: 10.3390/ph13030040
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Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials
 • 2019  • DOI: 10.1002/cncr.31719
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Erythropoietic Protoporphyria and X-Linked Protoporphyria: pathophysiology, genetics, clinical manifestations, and management
 • 2019  • DOI: 10.1016/j.ymgme.2019.01.020
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Congenital erythropoietic porphyria: Recent advances
 • 2019  • DOI: 10.1016/j.ymgme.2018.12.008
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The Science of Obesity Management: An Endocrine Society Scientific Statement
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Current and future pharmacological therapies for NAFLD/NASH
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Obesity: Pathophysiology and Management
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The Parabrachial Nucleus: CGRP Neurons Function as a General Alarm
 • 2018  • DOI: 10.1016/j.tins.2018.03.007
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Peptidomimetic therapeutics: scientific approaches and opportunities
 • 2017  • DOI: 10.1016/j.drudis.2016.11.003
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Afamelanotide: A Review in Erythropoietic Protoporphyria
 • 2016  • DOI: 10.1007/s40257-016-0184-6
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Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians
 • 2009  • DOI: 10.1002/ijc.24327
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Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations
 • 2018  • DOI: 10.1038/s41598-018-27145-2
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Regenerative Medicine Approaches to Craniofacial and Corneal Neuropathic Pain
 • 2026  • DOI: 10.3390/ph19050692
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Targeting Peptidergic Systems for Melanoma Treatment
 • 2026  • DOI: 10.3390/cancers18091347
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Analysis of the structural diversity of heterocycles amongst European medicines agency approved pharmaceuticals (2014-2023)
 • 2025  • DOI: 10.1039/d5md00403a
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The role and value of real-world evidence in health technology decision-making in France, Germany, Italy, Spain, and the UK: insights on external control arms
 • 2025  • DOI: 10.1017/s0266462324004720
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Update on Melasma-Part I: Pathogenesis
 • 2022  • DOI: 10.1007/s13555-022-00779-x
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Signal pathways of melanoma and targeted therapy
 • 2021  • DOI: 10.1038/s41392-021-00827-6
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Nuts and bolts of the salt-inducible kinases (SIKs)
 • 2021  • DOI: 10.1042/bcj20200502
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Participation of keratinocyte- and fibroblast-derived factors in melanocyte homeostasis, the response to UV, and pigmentary disorders
 • 2021  • DOI: 10.1111/pcmr.12985
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Photoprotection according to skin phototype and dermatoses: practical recommendations from an expert panel
 • 2021  • DOI: 10.1111/jdv.17242
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Visible light. Part II: Photoprotection against visible and ultraviolet light
 • 2021  • DOI: 10.1016/j.jaad.2020.11.074
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Afamelanotide: An Orphan Drug with Potential for Broad Dermatologic Applications
 • 2021  • DOI: 10.36849/jdd.5526
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Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma
 • 2020  • DOI: 10.3390/ijms21176129
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Ultraviolet Radiation and Melanomagenesis: From Mechanism to Immunotherapy
 • 2020  • DOI: 10.3389/fonc.2020.00951
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Emerging Strategies to Protect the Skin from Ultraviolet Rays Using Plant-Derived Materials
 • 2020  • DOI: 10.3390/antiox9070637
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Relevance of Vitamin D in Melanoma Development, Progression and Therapy
 • 2020  • DOI: 10.21873/anticanres.13976
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Illuminating insights into opsin 3 function in the skin
 • 2020  • DOI: 10.1016/j.jbior.2019.100668
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MITF and UV responses in skin: From pigmentation to addiction
 • 2019  • DOI: 10.1111/pcmr.12726
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Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs
 • 2019  • DOI: 10.3390/molecules24081516
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MITF-the first 25 years
 • 2019  • DOI: 10.1101/gad.324657.119
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Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential
 • 2018  • DOI: 10.1016/j.tem.2018.08.004
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MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair
 • 2018  • DOI: 10.3390/ijms19092667
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Immune and molecular correlates in melanoma treated with immune checkpoint blockade
 • 2017  • DOI: 10.1002/cncr.30444
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Advances in the management of erythropoietic protoporphyria - role of afamelanotide
 • 2016  • DOI: 10.2147/tacg.s122030
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Melanocortin 1 Receptor: Structure, Function, and Regulation
 • 2016  • DOI: 10.3389/fgene.2016.00095
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The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders
 • 2016  • DOI: 10.3390/ijms17020160
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Protoporphyrin IX: the Good, the Bad, and the Ugly
 • 2016  • DOI: 10.1124/jpet.115.228130
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A review of common tanning methods
 • 2015
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MC1R, eumelanin and pheomelanin: their role in determining the susceptibility to skin cancer
 • 2015  • DOI: 10.1111/php.12335
View Source

60 sources · Platform research library · Not generated by AI

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Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.