Melanotan 1
Synthetic linear alpha-MSH analogue — EMA/FDA-approved (Scenesse) for erythropoietic protoporphyria (EPP). Distinct from Melanotan II: linear structure, no sexual side effects.
🔬 Mechanism of Action
Melanotan 1 (afamelanotide) is a linear 13-amino-acid synthetic analogue of α-melanocyte-stimulating hormone (α-MSH), with two substitutions: [Nle4, D-Phe7]. These modifications confer >100× greater potency and enzymatic stability compared to native α-MSH. Afamelanotide is a selective MC1R agonist — it activates melanocortin 1 receptors on melanocytes, triggering the cAMP → CREB → MITF → tyrosinase pathway that increases eumelanin (brown/black pigment) synthesis. Unlike Melanotan II, afamelanotide does not significantly activate MC3R or MC4R, so it lacks the appetite-suppressive, erectile, and CNS effects of MT-II. Administered as a sub-dermal implant, it provides sustained tanning and photoprotection.
Source: PMID: 19706843
📜Background & History
Melanotan 1 (afamelanotide) was developed at the University of Arizona in the 1980s as part of research into α-MSH analogues for photoprotection. Unlike Melanotan II (a cyclic heptapeptide with broad melanocortin receptor activity), MT-1 is a linear tridecapeptide selective for MC1R. It was approved by the EMA in 2014 and FDA in 2019 as Scenesse (a 16 mg sub-dermal implant) for erythropoietic protoporphyria (EPP), an inherited condition causing severe photosensitivity.
🎯 Research Use Cases
- ✓Erythropoietic protoporphyria (EPP)
- ✓Photoprotection research
- ✓Skin cancer prevention research
💉 Dosing Protocol
| Typical Dose | 16 mg implant (sub-dermal, every 60 days) |
| Frequency | Every 60 days (implant) |
| Half-Life | 0.5 hours |
⚠️Safety & Considerations
FDA/EMA-approved as Scenesse (16mg implant) specifically for EPP — an orphan drug with limited general availability. Common side effects include nausea, headache, and darkening of pre-existing nevi (moles). All nevi should be monitored dermatologically. Not to be confused with Melanotan II, which has more systemic effects.
⚡Interactions & Contraindications
Monitor pre-existing nevi for changes. May darken existing moles. Not for use with phototherapy. No significant drug interactions reported at approved doses.
🔗Synergies & Common Stacks
MT-1 and MT-2 both stimulate melanogenesis but through different receptor selectivity profiles. MT-1 is the clinically approved, selective compound; MT-2 is the broader-acting research peptide.