Skin & Hair

Melanotan I

Afamelanotide, CUV1647, Scenesse, MT-1

Melanotan I (afamelanotide) is a synthetic alpha-MSH analog that stimulates melanin production across the body for protective and cosmetic tanning. It is FDA-approved as Scenesse for erythropoietic protoporphyria (EPP) and lacks the aphrodisiac effects of Melanotan II.

Subcutaneous (SubQ) Intermediate
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This peptide profile is for research and educational purposes only. Not intended for human use or self-administration.

Overview

Melanotan I, also known as afamelanotide, is a synthetic linear analogue of alpha-melanocyte-stimulating hormone (α-MSH) — the natural peptide that controls skin pigmentation. Unlike Melanotan II (which has a cyclic structure and melanocortin-4 receptor activity responsible for sexual arousal effects), Melanotan I is a linear peptide with higher selectivity for the MC1R (melanocortin-1 receptor) on melanocytes, producing a more targeted pigmentation effect with fewer off-target CNS effects. It was approved in Europe (2010) and the US (2019) as Scenesse for Erythropoietic Protoporphyria — a rare genetic condition causing severe phototoxic reactions — by providing protective baseline melanin before sun exposure.

Mechanism of Action

Melanotan I binds to MC1R (melanocortin-1 receptor) on melanocytes, stimulating adenylyl cyclase via Gs-protein coupling, which increases intracellular cAMP. This triggers the activation of tyrosinase — the key enzyme in melanin synthesis — and drives the production of eumelanin (the dark, UV-protective form of melanin) within melanosomes. The resulting tan provides significant photoprotection as eumelanin absorbs UV radiation before it can damage DNA. Unlike UV-induced tanning, which requires DNA damage as the signal, Melanotan I produces melanin via the natural hormonal pathway without requiring UV exposure as a trigger. MC1R selectivity means it does not meaningfully activate MC3R or MC4R, avoiding the appetite suppression and sexual arousal effects of Melanotan II.

Key Research

Afamelanotide (Scenesse) completed multiple Phase 2 and Phase 3 clinical trials for EPP in the EU and US. The EU Phase 3 trial (N=93) showed patients could tolerate significantly more sun exposure without pain (median 6 hours vs 0.75 hours placebo). Approved by EMA in 2010 and FDA in 2019. Phase 2 studies in solar urticaria, polymorphic light eruption, and vitiligo showed promising results. Historical tanning studies (University of Arizona, 1990s) established melanogenesis dose-response and formed the basis for subsequent melanocortin peptide research. Bioavailability of subcutaneous injection is high; the approved EPP formulation is a biodegradable subcutaneous implant for sustained release.

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Research Dosing

Typical Dose

0.5–1.5 mg subcutaneously every 2–3 months (EPP approved); research tanning protocols use 0.5–1 mg d

Half-Life

~18 hours (standard) → extended release implant in EPP appro

For tanning research, the typical protocol uses a daily subcutaneous injection of 0.5–1 mg for 7–10 consecutive days (loading phase), followed by maintenance doses of 0.5 mg every 3–5 days. Sun or UV exposure during the loading phase enhances results but is not required for pigmentation to occur. Always use SPF sun protection even when tanned, as Melanotan I does not prevent UV-induced DNA damage despite reducing visible burn. The EPP clinical dose is a 16 mg biodegradable implant every 2 months — a significantly different delivery method from research subcutaneous use.
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Protocols

Tanning Protocol: 0.5–1 mg SC daily for 7–10 days, then 0.5 mg every 3–5 days for maintenance. Combine with moderate sun exposure (15–30 minutes daily) during loading phase for enhanced melanin activation. Photoprotection Protocol (EPP research context): use per supervised clinical framework — the approved implant format is used in clinical care and not recreated with raw peptide.

Reported Side Effects

Side effects summarized from animal studies and researcher community observations. Educational purposes only — not medical advice.
Melanotan I is notably better tolerated than Melanotan II. The most common side effects are transient facial flushing (warm sensation, redness) lasting 30–60 minutes post-injection, mild nausea, and fatigue in the first few days of loading. Yawning and mild drowsiness are occasionally reported. Spontaneous erections and increased libido — common with Melanotan II — are rare or absent with Melanotan I due to its MC1R selectivity over MC4R. Hyperpigmentation of moles (increase in darkness and sometimes size) is a consistent finding and warrants dermatological monitoring. New or changing moles during use should be evaluated by a dermatologist.

Storage & Handling

Store lyophilized Melanotan I at 2–8°C, protected from light. Stable for up to 12 months in lyophilized form. Reconstitute with bacteriostatic water (a 10 mg vial + 2 mL BAC water yields 5 mg/mL, or 500 mcg per 0.1 mL on U-100 syringe). Store reconstituted solution at 2–8°C and use within 28 days. Keep away from heat and direct light, which accelerate degradation.