Afamelanotide (Scenesse, Melanotan I)

FDA-approved context Skin & Hair 3 sources

Afamelanotide is a synthetic analogue of alpha-melanocyte stimulating hormone (α-MSH) that stimulates melanin production in the skin. It is FDA-approved under the brand name Scenesse to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). Research also explores its potential in other photosensitivity disorders and vitiligo.

01Dosing reference

Amount

16 mg (as Scenesse implant) or 1-2 mg/day (research peptide form)

Frequency

Every 2 months (implant) or daily (research peptide)

Cycle

Ongoing as needed for photoprotection (implant) or 2-4 weeks (research peptide)

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

MC1R Activation

Afamelanotide binds to the melanocortin-1 receptor (MC1R) on melanocytes in the skin.

Melanin Synthesis

Activation of MC1R stimulates the production of eumelanin, a dark pigment that absorbs and scatters UV radiation.

Photoprotection

Increased eumelanin levels provide a physical barrier against sunlight, reducing phototoxic reactions in sensitive individuals.

03Human evidence

Afamelanotide significantly increases the duration of pain-free sunlight exposure in patients with erythropoietic protoporphyria (EPP).

Demonstrated in multiple Phase III randomized, double-blind, placebo-controlled trials leading to FDA and EMA approval.

Combination therapy of afamelanotide and narrowband UVB phototherapy enhances repigmentation in patients with vitiligo.

Observed in clinical trials comparing combination therapy to narrowband UVB alone, showing faster and more extensive repigmentation.

04Preclinical evidence

Afamelanotide protects skin cells from UV-induced DNA damage and apoptosis.

In vitro studies on human melanocytes and keratinocytes exposed to UV radiation.

The peptide exhibits anti-inflammatory properties by modulating cytokine release.

Animal models of skin inflammation and UV exposure.

05What is known vs. unknown

Reasonably established

FDA-approved as Scenesse (a subcutaneous implant) for erythropoietic protoporphyria (EPP).
Stimulates eumelanin production, providing systemic photoprotection.
Has a longer half-life and greater potency than natural α-MSH.
Investigated for use in vitiligo, solar urticaria, and polymorphic light eruption.

Unknowns & limits

Long-term safety of continuous, lifelong use in EPP patients is still being monitored.
Optimal dosing and efficacy for cosmetic tanning or non-approved dermatological conditions remain unestablished and carry risks.
Potential effects on melanoma risk require ongoing surveillance, though current data does not show an increased risk.

06Safety & regulatory context

Regulatory statusAfamelanotide is FDA-approved as a prescription implant (Scenesse) for EPP. Common side effects include nausea, headache, nasopharyngitis, back pain, and injection site reactions. Because it stimulates melanocytes, there is a theoretical concern regarding the darkening of existing moles or the development of melanoma, necessitating regular full-body skin examinations. The unregulated use of 'Melanotan I' from compounding pharmacies or research chemical suppliers for cosmetic tanning is not approved by the FDA and carries significant risks of contamination, inaccurate dosing, and adverse effects.

07Compared with Melanotan II

Afamelanotide (Scenesse, Melanotan I) vs. Melanotan II

Key difference

Afamelanotide (Melanotan I) is primarily selective for MC1R and is FDA-approved for EPP, whereas Melanotan II crosses the blood-brain barrier, binds to multiple melanocortin receptors (including MC3R and MC4R), and causes significant sexual arousal and appetite suppression.

When researchers discuss each

Researchers discuss Afamelanotide in the context of clinical photoprotection and dermatological disorders, while Melanotan II is often discussed regarding its off-target effects on libido and its widespread unregulated use for cosmetic tanning.

08Glossary

Erythropoietic Protoporphyria (EPP)

A rare genetic metabolic disorder characterized by severe, painful skin reactions to sunlight.

Melanocortin-1 Receptor (MC1R)

A protein on the surface of specialized skin cells that, when activated, triggers the production of melanin.

Eumelanin

The most abundant type of human melanin, responsible for brown and black pigmentation and providing UV protection.

09Knowledge check

Q1What is the primary mechanism by which afamelanotide provides photoprotection?

Q2For which condition is afamelanotide FDA-approved under the brand name Scenesse?

Q3Which of the following is a documented limitation in the dossier's evidence about afamelanotide?

Q4According to the dossier comparison, what is a key difference between afamelanotide (Melanotan I) and Melanotan II?

Q5Which safety or regulatory recommendation or warning is specifically included in the dossier for afamelanotide use?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.