Melanotan I
Also known as: Afamelanotide, CUV1647, Scenesse (FDA-approved formulation)
Also known as Afamelanotide, this melanocortin receptor agonist induces skin pigmentation and provides photoprotection. FDA-approved for erythropoietic protoporphyria (EPP) under the brand name Scenesse.
Research Status
Extensive Clinical Data
For research purposes only. Not approved for human use. Not medical advice.
Research Areas
Side Effects
Occurs in a small percentage of users, typically within the first few hours after injection. Usually self-resolving. Taking the injection with food or at bedtime may reduce incidence. Afamelanotide has a lower incidence of nausea compared to Melanotan II due to MC1R selectivity.
Transient redness or warmth in the face, typically occurring within 1–2 hours of injection and resolving within 30 minutes to 2 hours. More common at higher doses or in individuals with fair skin.
Localized redness, warmth, or mild swelling at the injection site, typically resolving within 24 hours. Minimize by rotating injection sites, allowing the solution to reach room temperature, and using proper injection technique. Apply ice if needed.
Mild itching at the injection site, usually transient. Avoid scratching to prevent skin damage. Antihistamine cream may provide relief if bothersome.
Mild headache reported in a small percentage of users, typically occurring within hours of injection and resolving within 24 hours. Hydration and over-the-counter analgesics may help.
Afamelanotide stimulates melanin production systemically, which may darken pre-existing moles and freckles. This is expected and generally reversible upon discontinuation. Users with numerous or atypical moles should consult a dermatologist before use and undergo baseline skin examination.
Rare in users of afamelanotide due to MC1R selectivity; more common with non-selective melanocortin agonists like Melanotan II. If occurs, typically self-resolving and not requiring intervention.
Rare with afamelanotide due to MC1R selectivity; MC3R and MC4R agonism (which afamelanotide minimally engages) are responsible for appetite effects seen with non-selective melanocortin agonists.
In erythropoietic protoporphyria patients, afamelanotide is used specifically to reduce phototoxic reactions. However, inadequate melanin induction or continued high UV exposure may still trigger reactions. Requires medical evaluation and adjustment of sun protection strategies.
Rare but possible; may include urticaria, angioedema, or anaphylaxis. Seek immediate medical attention if signs of allergy develop (difficulty breathing, throat tightness, severe rash). Discontinue use immediately.
Dosing Reference
| Parameter | Value |
|---|---|
| Dose range | 0.5-1 mg |
| Frequency | 1x daily |
| Timing | Any time of day; consistent timing recommended for research tracking |
| Route | Subcutaneous |
Subcutaneous injection. Start at 0.5 mg and titrate based on pigmentation response. More selective for MC1R than Melanotan II, resulting in fewer off-target effects. For research purposes only.
Research disclaimer
Figures drawn from published research literature and community logs. Not clinical recommendations. Consult a qualified professional. Research use only.
Reconstitution Guide
Do not use saline or bacteriostatic saline — use only bacteriostatic water for reconstitution
Do not shake the vial vigorously; gentle swirling prevents peptide degradation
Discard immediately if the solution appears cloudy, discolored, or contains visible particles
Use within 30 days of reconstitution when stored at 2–8°C
Do not freeze the reconstituted solution; freezing may denature the peptide
Use the PeptideVolt reconstitution calculator for your exact concentration
Molecular and Pharmacological Data
| Molecular weight | 1817.9 Da |
| Half-life | Approximately 2–3 hours (in vivo); longer tissue retention due to MC1R binding |
| Sequence | Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 |
Melanotan I (afamelanotide) is a selective melanocortin-1 receptor (MC1R) agonist that mimics alpha-melanocyte-stimulating hormone (α-MSH). Upon binding to MC1R on melanocytes, it triggers a signaling cascade that increases intracellular cAMP, leading to upregulation of tyrosinase and enhanced melanin synthesis and transfer to keratinocytes. This results in increased skin pigmentation and provides photoprotection by increasing the eumelanin (protective pigment) content of the skin, reducing UV-induced DNA damage and apoptosis.
MC1R-cAMP Signaling
Afamelanotide binds to melanocortin-1 receptors on melanocytes, activating G-protein-coupled receptor signaling that increases intracellular cAMP levels. Elevated cAMP activates protein kinase A (PKA), which phosphorylates CREB (cAMP response element binding protein) and other transcription factors, leading to upregulation of tyrosinase and other melanogenic enzymes.
Melanin Synthesis and Transfer
Increased tyrosinase activity catalyzes the conversion of L-tyrosine to L-DOPA and subsequently to melanin (eumelanin and pheomelanin). Melanin is packaged into melanosomes and transferred to neighboring keratinocytes, resulting in visible skin darkening and increased UV absorption capacity.
Photoprotection via Antioxidant Activity
Eumelanin acts as a broad-spectrum UV absorber and free radical scavenger, reducing oxidative stress and DNA damage from UV exposure. This mechanism is particularly important in erythropoietic protoporphyria, where increased melanin provides a physical and chemical barrier against photosensitivity.
- Afamelanotide is more selective for MC1R than Melanotan II, resulting in fewer off-target effects on other melanocortin receptors (MC3R, MC4R, MC5R)
- MC1R selectivity reduces unwanted systemic effects such as appetite stimulation, sexual dysfunction, and nausea commonly associated with non-selective melanocortin agonists
- The peptide induces both constitutive and inducible melanin synthesis, providing baseline pigmentation and enhanced UV response
- Photoprotection is achieved through both increased melanin content and upregulation of antioxidant defense mechanisms in melanocytes and keratinocytes
- FDA approval for erythropoietic protoporphyria (Scenesse) is based on demonstrated reduction in phototoxic reactions and improved quality of life in EPP patients
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