Melanotan I
Melanocortin PeptideapprovedAlso known as: Afamelanotide, Scenesse, NDP-α-MSH, CUV1647
A synthetic analog of alpha-melanocyte stimulating hormone (α-MSH) that stimulates melanin production for photoprotection, FDA-approved (as Scenesse) for erythropoietic protoporphyria (EPP).
Overview
Melanotan I (afamelanotide) is a synthetic 13-amino acid linear peptide analog of α-MSH developed at the University of Arizona. It is a potent, non-selective melanocortin receptor agonist with highest affinity for MC1R, the primary receptor controlling melanogenesis. Unlike its cyclic relative Melanotan II, MT-I is a linear peptide that acts more selectively on tanning pathways with fewer sexual and appetite-related side effects. It was approved by the FDA in 2019 under the brand name Scenesse as a subcutaneous implant for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare genetic disorder. Melanotan I increases eumelanin (protective dark pigment) production in the skin, providing photoprotection independent of UV exposure. It has been researched for skin cancer prevention, vitiligo, and polymorphous light eruption.
Mechanism of Action
Melanotan I acts through melanocortin receptor signaling: (1) Binds to MC1R on melanocytes, activating adenylyl cyclase and increasing cAMP levels; (2) Activates the MITF transcription factor, upregulating tyrosinase and melanin synthesis enzymes; (3) Promotes production of eumelanin (brown/black protective pigment) over pheomelanin (red/yellow pigment); (4) Provides photoprotection by increasing the skin's natural UV absorption capacity; (5) Has anti-inflammatory effects mediated through MC1R on immune cells; (6) May have antioxidant properties through melanin-mediated free radical scavenging.
Molecular Formula
C78H111N21O19
Molecular Weight
1646.85 g/mol
Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
Dosage Protocols
Dose Range
16mg – 16mg
Frequency
Every 60 days
Route
subcutaneous implant
Cycle Length
As needed seasonally (typically before/during UV exposure periods)
Scenesse implant is placed subcutaneously above the iliac crest by a healthcare provider. Each implant delivers 16mg over ~60 days.
Source: FDA-approved prescribing information
Side Effects
| Effect | Severity |
|---|---|
| Nausea | mild |
| Facial flushing | mild |
| Darkening of existing moles | moderate |
| Headache | mild |
| Injection site reaction | mild |
Pros & Cons
FDA and EMA-approved pharmaceutical with established safety profile from clinical trials
Provides genuine photoprotection by increasing eumelanin production independent of UV exposure
More selective for MC1R than Melanotan II, resulting in fewer sexual and appetite side effects
Potential skin cancer prevention through enhanced natural UV defense
Approved implant (Scenesse) is extremely expensive and only available for EPP diagnosis
Darkening of moles raises concerns about masking melanoma detection
Less potent tanning effect per dose compared to Melanotan II
Long-term safety of off-label cosmetic use not well established
Research Studies
Legal Status
FDA-approved as Scenesse (afamelanotide) implant for EPP. EMA-approved since 2014. Prescription-only for approved indication. Also available as a research chemical for non-approved uses. Banned by WADA.
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