Description
Melanotan 1 (Afamelanotide) — Research & Data
A linear analog of α-MSH with higher selectivity for MC1R than MT2. Afamelanotide (MT1) is FDA-approved under the brand name Scenesse® for erythropoietic protoporphyria (EPP).
How Melanotan 1 (Afamelanotide) Works
Afamelanotide (MT1) is a linear, 13-amino-acid analog of α-MSH that selectively activates MC1R on melanocytes. MC1R activation triggers the cAMP-PKA-MITF pathway, leading to eumelanin synthesis. Unlike MT2, afamelanotide has minimal activity at MC3R-MC5R, resulting in fewer off-target effects on appetite, energy, and sexual function.
Mechanisms of Action
MC1R Selectivity
More selective for MC1R than MT2, providing targeted melanogenesis with fewer off-target melanocortin effects.
Eumelanin Synthesis
Stimulates eumelanin (brown/black pigment) production, the photoprotective form of melanin.
Photoprotection
Reduces phototoxic reactions in EPP patients by increasing skin melanin density before UV exposure.
What Research Has Shown
Phase 3 trials in 93 EPP patients showed significantly increased pain-free time in sunlight. In fair-skinned individuals, afamelanotide increased melanin density and provided measurable UV protection without UV exposure. It is the first melanocortin therapy to receive FDA approval (2019, Scenesse®).
Dosing Information from Research
FDA-approved dosing: 16 mg implant inserted subcutaneously every 2 months. Research protocols with injectable form: 0.16-1 mg subcutaneously daily. Implant provides sustained, steady-state drug delivery.
Pharmacokinetics
Injectable: half-life approximately 30 minutes. Implant: provides sustained release over approximately 60 days. Peak melanogenic effect occurs 2-4 weeks after implant insertion. Melanin elevation persists 2-3 months after implant depletion.
How It Works in the Body
Afamelanotide binds MC1R with high selectivity, activating adenylyl cyclase and increasing intracellular cAMP. This activates PKA, which phosphorylates CREB and upregulates MITF transcription factor. MITF drives expression of melanogenic enzymes (tyrosinase, TRP-1, TRP-2) that convert tyrosine to eumelanin. The increased eumelanin absorbs UV radiation, protecting against DNA damage and phototoxic reactions.
Important Notes
- Afamelanotide (Scenesse®) is FDA-approved for erythropoietic protoporphyria (EPP) — a rare light sensitivity disorder.
- It is more MC1R-selective than MT2, resulting in fewer off-target effects.
- The implant formulation (16 mg) provides sustained release over 60 days.
- MT1 does not typically cause nausea or appetite changes at the same rate as MT2.
Safety Profile from Research
What clinical studies report
Well-characterized safety from Phase 3 trials. Most common adverse events: implant site reaction (26%), nausea (11%), headache (8%), oropharyngeal pain (7%). Generally mild and transient.
Common Digestive Issues
Nausea in 11% of patients — significantly lower than MT2 (75-85%) due to MC1R selectivity.
Treatment Discontinuation Rates
Less than 5% in Phase 3 trials. Most patients continued treatment across multiple implant cycles.
Study Exclusion Criteria
Patients with hepatic dysfunction, active skin malignancy, or hypersensitivity to α-MSH analogs were excluded.
Researcher Notes
- Afamelanotide is the gold standard for selective MC1R research.
- Compare with non-selective MT2 to study the role of specific melanocortin receptors.
- The implant formulation is only available through the approved prescribing pathway (Scenesse®).
- Injectable research-grade MT1 is available for laboratory studies.
Compound Information
Storage Requirements
Lyophilized
Store at 2-8°C. Protect from light and moisture.
Reconstituted
Use within 14 days when stored at 2-8°C.
Light Sensitivity
Light-sensitive. Store in original packaging in dark conditions.
Research Status — Where It Stands
FDA-approved (Scenesse®, 2019) for EPP. EMA-approved since 2014. Ongoing research for polymorphous light eruption, vitiligo, and photoprotection in organ transplant recipients. The most clinically advanced melanocortin peptide.
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