Melanotan I (Afamelanotide)

What it is

Melanotan I (afamelanotide) is a more MC1R-selective melanocortin agonist. MC1R is the melanocortin 1 receptor, the receptor that drives melanin production in skin pigment cells. It is the basis of the approved drug Scenesse, a subcutaneous implant that the FDA approved in 2019 to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria (EPP), a rare photosensitivity disorder.

Outside that approved use, injected Melanotan I is also used for tanning, with fewer libido and appetite effects than Melanotan II. In the PeptidesAI encyclopedia it is categorized under skin and anti-aging.

How it's thought to work

Melanotan I selectively activates MC1R to stimulate eumelanin production, the dark form of melanin, which increases skin pigmentation and photoprotection. It has less MC4R activity than Melanotan II, so it produces fewer arousal and appetite effects.

What the research says

The approved drug afamelanotide (Scenesse) is FDA-approved for erythropoietic protoporphyria as an implant. Its approval followed two randomized, double-blind, placebo-controlled trials published in 2015 (74 patients in the European Union and 94 in the United States), in which afamelanotide was associated with longer pain-free time in sunlight than placebo: a median of 69.4 versus 40.8 hours at 6 months in the US trial, and 6.0 versus 0.8 hours at 9 months in the EU trial. Adverse events were mostly mild.

Injected Melanotan I for tanning is not FDA-approved. A 2017 review linked unregulated use of melanotan I and II to changes in existing moles and new atypical moles.

Reported side effects

Reported side effects include nausea and flushing, which are milder than with Melanotan II, and possible mole and skin darkening. It has fewer libido and appetite effects than Melanotan II. The Scenesse label lists skin hyperpigmentation and darkening of pre-existing nevi (moles) among its effects, and in the pivotal trials adverse events were mostly mild.

Reconstitution

The approved afamelanotide product, Scenesse, is a subcutaneous implant and is not reconstituted. The vial figures below describe freeze-dried Melanotan I sold outside that approved product, which commonly comes in 10 mg vials.

Worked example. A 10 mg vial is 10,000 mcg. Reconstituted with 2 mL of BAC water, that works out to 10,000 mcg ÷ 2 mL = 5,000 mcg/mL. On a U-100 insulin syringe, where each unit is 0.01 mL, each unit holds 5,000 × 0.01 = 50 mcg. Use the peptide reconstitution calculator to work out the concentration and units for any vial size and water volume.

Important notes

Injected tanning use of Melanotan I is not FDA-approved. Because it can darken moles and skin, skin changes are a recognized concern, and the Scenesse label itself lists darkening of pre-existing nevi.

Sources

1. SCENESSE (afamelanotide) implant, for subcutaneous use: prescribing information. U.S. Food and Drug Administration, 2019. Fda label
2. Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG et al. N Engl J Med, 2015. Human trial
3. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Habbema L et al. Int J Dermatol, 2017. Review

How we choose and check sources

Frequently asked questions

These questions cover the same ground as the sections above, in a shorter format.

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