Melanotan I
Also known as: Afamelanotide, Scenesse, NDP-α-MSH, [Nle4, D-Phe7]-α-MSH, CUV1647
Melanotan I (Afamelanotide) is a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH) that activates MC1R to stimulate melanogenesis. FDA-approved as Scenesse for erythropoietic protoporphyria (EPP), it increases eumelanin production providing photoprotection without UV exposure.
Melanotan I is a 1,646.85 Da research peptide. Melanotan I (Afamelanotide) is a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH) that activates MC1R to stimulate melanogenesis. FDA-approved as Scenesse for erythropoietic protoporphyria (EPP), it increases eumelanin production providing photoprotection without UV exposure.
Also called: Afamelanotide, Scenesse, NDP-α-MSH
1,646.85
Molecular Weight
Daltons
3
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
16000-16000
Typical Dose
mcg
Overview
Melanotan I, clinically known as Afamelanotide and marketed as Scenesse, is a synthetic 13-amino acid peptide analog of alpha-melanocyte-stimulating hormone (α-MSH). It was developed at the University of Arizona by Victor Hruby and Mac Hadley in the 1980s through structure-activity relationship studies that produced a superpotent, enzyme-resistant analog of the natural melanocortin peptide. The key modifications; substitution of norleucine at position 4 and D-phenylalanine at position 7, confer dramatically increased potency and metabolic stability compared to native α-MSH. Melanotan I selectively activates the melanocortin 1 receptor (MC1R) on melanocytes, stimulating the production of eumelanin (the brown-black photoprotective pigment) rather than pheomelanin (the red-yellow pigment associated with sun sensitivity). It received EMA approval in 2014 and FDA approval in 2019 as Scenesse (16 mg subcutaneous implant) for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare genetic condition causing severe light sensitivity. Beyond EPP, Melanotan I has been researched for vitiligo, polymorphous light eruption, solar urticaria, and photoprotection in fair-skinned populations at high risk of UV-induced skin cancer.
Key Takeaways: Melanotan I
- Strongest evidence supports Melanotan I for fda-approved photoprotection (epp) and eumelanin production (tanning)
- Research doses typically range from 16000 to 16000 mcg via subcutaneous implant (physician-administered)
- 3 benefits with strong evidence, 2 moderate, 0 preliminary
- Half-life: ~30 minutes (IV); Scenesse implant provides sustained release over 60 days
- 5 cited research studies in this guide
Mechanism of Action
Melanotan I is a potent and selective agonist of the melanocortin 1 receptor (MC1R), a Gs-coupled GPCR expressed on epidermal melanocytes. MC1R activation stimulates adenylyl cyclase, increasing intracellular cAMP which activates protein kinase A (PKA). PKA phosphorylates CREB (cAMP response element-binding protein), which translocates to the nucleus and activates transcription of MITF (microphthalmia-associated transcription factor) — the master regulator of melanocyte biology. MITF upregulates the expression of melanogenic enzymes: tyrosinase (the rate-limiting enzyme), tyrosinase-related protein 1 (TRP-1), and dopachrome tautomerase (DCT/TRP-2). These enzymes drive the conversion of tyrosine → DOPA → dopaquinone → eumelanin within melanosomes. Critically, MC1R activation shifts melanin synthesis toward eumelanin (photoprotective brown-black pigment) and away from pheomelanin (photo-damaging red-yellow pigment that generates reactive oxygen species under UV). The increased eumelanin is transferred to surrounding keratinocytes via melanosome transport, providing distributed photoprotection across the epidermis. Melanotan I's selectivity for MC1R over other melanocortin receptors (MC3R, MC4R, MC5R) means it produces tanning with minimal effects on appetite, sexual function, or other melanocortin-mediated pathways, a key distinction from Melanotan II.
Research Benefits
Melanotan I at a Glance
Melanotan I is a potent and selective agonist of the melanocortin 1 receptor (MC1R), a Gs-coupled GPCR expressed on epidermal melanocytes.
FDA-Approved Photoprotection (EPP)
Strong EvidenceScenesse is FDA/EMA-approved for erythropoietic protoporphyria, providing photoprotection that allows EPP patients to tolerate sunlight exposure with significantly reduced phototoxic reactions.
Eumelanin Production (Tanning)
Strong EvidencePotently stimulates eumelanin synthesis in melanocytes, producing skin darkening (tan) without requiring UV exposure. Shifts melanin balance from pheomelanin toward photoprotective eumelanin.
MC1R Selectivity (Fewer Side Effects)
Strong EvidenceUnlike Melanotan II, Melanotan I is selective for MC1R with minimal activity at MC3R/MC4R, avoiding significant effects on appetite, sexual function, or blood pressure.
UV Damage Reduction
Moderate EvidenceIncreased eumelanin provides natural photoprotection against UV-induced DNA damage, potentially reducing skin cancer risk in high-risk populations.
Vitiligo Repigmentation
Moderate EvidenceClinical studies show Melanotan I combined with narrowband UVB promotes repigmentation in vitiligo patients, stimulating melanocyte activity in depigmented patches.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| Scenesse implant (FDA-approved for EPP) | 16000–16000 mcg | Subcutaneous implant (physician-administered) |
| Subcutaneous injection (research) | 500–1000 mcg | Subcutaneous injection |
| Vitiligo research protocol | 1000–1000 mcg | Subcutaneous injection combined with NB-UVB |
Frequency
Scenesse: one implant every 60 days. SC injection: once daily in research protocols.
Timing
No specific timing requirements. Scenesse implant provides continuous release.
Cycle Length
Scenesse: ongoing bimonthly implants. Research: 10-30 day courses.
Research Notes
- 1Scenesse is a 16 mg biodegradable implant inserted subcutaneously by a healthcare provider.
- 2The implant provides sustained release over approximately 60 days.
- 3Scenesse is approved only for EPP; it is not approved for cosmetic tanning.
- 4Melanotan I is more selective for MC1R than Melanotan II, with a cleaner side effect profile.
- 5Tanning effect develops gradually over days to weeks.
- 6Skin darkening occurs without UV exposure but is enhanced by UV.
Reconstitution Guide
Standard Reconstitution
Vial Size
10 mg
Bacteriostatic Water
2 mL
Concentration
50 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Melanotan I vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C) after reconstitution. Up to 30 days refrigerated.
Storage Temperature
Refrigerated (2-8°C) after reconstitution
Shelf Life
Up to 30 days refrigerated
Important Notes
- •Scenesse comes as a pre-formed implant — no reconstitution needed.
- •Research-grade lyophilized Melanotan I: reconstitute with bacteriostatic water.
- •Protect from light.
- •Store lyophilized powder frozen or refrigerated.
Melanotan I Dosing Calculator
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Melanotan I Reconstitution Calculator
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Safety & Side Effects
Reported Side Effects
- !Nausea (most common, especially initially; 17-22% in Scenesse trials)
- !Skin darkening (expected pharmacological effect, may be uneven initially)
- !Headache
- !Injection/implant site reactions (pain, redness, discoloration at implant site)
- !Fatigue
- !Darkening of pre-existing moles and freckles (requires dermatological monitoring)
- !Lip and gum hyperpigmentation
- !No significant effects on appetite or sexual function (MC1R selective)
- !Long-term melanocyte stimulation requires regular skin surveillance for melanocytic changes
Potential Interactions
- ⚡Patients on photosensitizing medications should be monitored closely.
- ⚡Anticoagulants: minor bruising risk at implant insertion site.
- ⚡No significant drug interactions identified in Scenesse clinical trials.
- ⚡May interact with other melanocortin receptor-active compounds.
- ⚡Regular dermatological surveillance recommended during treatment.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Afamelanotide for erythropoietic protoporphyria (Phase III)
key Phase III trial demonstrating Scenesse significantly increased pain-free sun exposure time and improved quality of life in EPP patients compared to placebo over 6 months.
Structure-activity relationships of superpotent melanotropin analogues
Original medicinal chemistry work characterizing NDP-α-MSH (Melanotan I) structure-activity relationships, establishing the Nle4/D-Phe7 substitutions that confer superpotency and metabolic stability.
Afamelanotide combined with NB-UVB for vitiligo
Controlled trial showing afamelanotide plus narrowband UVB produced superior and faster repigmentation in vitiligo compared to NB-UVB alone, particularly in darker skin types.
α-MSH analogs stimulate eumelanin synthesis and melanocyte photoprotection
Demonstrated NDP-α-MSH stimulates eumelanin production and reduces UV-induced DNA damage in human melanocytes, establishing the photoprotective mechanism beyond cosmetic tanning.
MC1R signaling and melanocyte biology: implications for melanoma prevention
Landmark study showing MC1R activation by α-MSH analogs produces UV-independent tanning and photoprotection, with direct implications for melanoma prevention strategies.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Melanotan I (Afamelanotide/Scenesse) is a synthetic α-MSH analog that activates MC1R to stimulate eumelanin production. It is FDA-approved for erythropoietic protoporphyria and produces skin darkening (tanning) with photoprotective properties.
Melanotan I is selective for MC1R (tanning receptor), while Melanotan II activates multiple melanocortin receptors (MC1R, MC3R, MC4R, MC5R). This means MT-I causes tanning with minimal other effects, while MT-II also affects sexual arousal, appetite, and blood pressure. MT-I has FDA approval; MT-II does not.
Yes. Scenesse is the brand name for afamelanotide (Melanotan I) formulated as a 16 mg biodegradable subcutaneous implant. It is the FDA/EMA-approved pharmaceutical product.
There is no evidence that Melanotan I causes melanoma. The eumelanin it produces is actually photoprotective. However, because it stimulates melanocytes, regular dermatological surveillance (skin checks, mole monitoring) is recommended during treatment as a precaution.
No. Melanotan I produces eumelanin and skin darkening without UV exposure. However, UV exposure enhances and accelerates the tanning response. For EPP patients, the benefit is increased tolerance to sunlight, not the tan itself.
Unlike Melanotan II, Melanotan I has minimal effects on appetite or sexual function because it is selective for MC1R. MC3R/MC4R (which mediate appetite and sexual effects) are not significantly activated by Melanotan I at therapeutic doses.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.