Melanotan I

Melanocortin Peptideapproved

Also 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

16mg16mg

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

EffectSeverity
Nauseamild
Facial flushingmild
Darkening of existing molesmoderate
Headachemild
Injection site reactionmild

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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