Peptide Schedule
Melanotan I13 residues (approx.)SYSMEHFRWGKPVEach bubble = one amino acid. Size = residue mass. Color = chemical class.Uses closest standard amino acids for non-standard residues.Melanotan I
Benefits
About Melanotan I
Melanotan I (afamelanotide) is a synthetic 13-amino-acid peptide analog of alpha-melanocyte stimulating hormone (alpha-MSH). It is the first and only FDA-approved melanocortin receptor agonist for increasing sun tolerance. Sold under the brand name Scenesse, it received FDA approval in October 2019 for the treatment of erythropoietic protoporphyria (EPP), a rare genetic disorder where patients experience severe phototoxic reactions to sunlight due to excess protoporphyrin IX accumulation. Unlike its shorter cousin Melanotan II, which activates multiple melanocortin receptor subtypes and produces sexual arousal, appetite suppression, and unpredictable side effects, Melanotan I is a selective MC1R agonist. This selectivity means it drives eumelanin production in melanocytes without the broad off-target effects seen with less selective analogs. The result is a genuine increase in brown-black eumelanin pigment that absorbs UV radiation and dissipates it as heat, providing real photoprotection from the inside out. In Phase 3 trials involving 168 EPP patients across the EU and US, afamelanotide-treated patients tolerated significantly more pain-free sun exposure (median 6.0 hours vs 0.8 hours in placebo, p=0.005) and experienced fewer phototoxic reactions (77 vs 146, p=0.04). In the research peptide community, injectable melanotan I is used at much lower doses (0.5-1.5 mg daily SC) for cosmetic tanning. Its superior MC1R selectivity and cleaner side effect profile make it a preferred option for users who want pigmentation changes without the nausea, flushing, or sexual effects associated with Melanotan II.
Who Should Consider Melanotan I
- Adults with erythropoietic protoporphyria (EPP) seeking increased sunlight tolerance
- Individuals with fair skin seeking increased melanin-based photoprotection
- People wanting cosmetic tanning with fewer side effects than Melanotan II
- Patients with sun sensitivity disorders requiring melanocortin-based therapy
How Melanotan I Works
Afamelanotide selectively binds and activates the melanocortin-1 receptor (MC1R) on melanocytes. MC1R activation triggers a Gs-protein signaling cascade that increases intracellular cAMP, activating protein kinase A (PKA) which phosphorylates CREB. Phosphorylated CREB upregulates MITF, the master regulator of melanogenesis, which drives expression of tyrosinase, TYRP1, and DCT — the three enzymes required for eumelanin synthesis. The net result is a shift from pheomelanin (red-yellow, photosensitizing) toward eumelanin (brown-black, photoprotective) production. Afamelanotide incorporates a norleucine substitution at position 4 and a D-phenylalanine at position 7, granting it resistance to enzymatic degradation and an apparent half-life of ~15 hours.
What to Expect
Implant releases the majority of the 16 mg dose. Plasma levels peak around 36 hours. MC1R signaling activates eumelanin synthesis. Mild nausea or headache may occur within the first 1-2 days.
Visible skin darkening begins as eumelanin accumulates in keratinocytes. Implant drug release is essentially complete by day 10.
Peak pigmentation achieved. Patients report increased tolerance to sun exposure and fewer phototoxic episodes.
Pigmentation begins to gradually fade as melanin-loaded keratinocytes are shed through normal skin turnover. Next implant due at the 60-day mark.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 500mcg | Daily |
| Moderate | 1mg | Daily |
| Aggressive | 1,500mcg | Daily |
Note: FDA-approved as Scenesse (16 mg subcutaneous implant) for erythropoietic protoporphyria (EPP). Scenesse implant administered every 60 days by a healthcare provider. Injectable research-grade melanotan I uses lower SC doses (0.5-1.5 mg daily). More MC1R-selective than Melanotan II with fewer sexual side effects.
How to Inject Melanotan I
Scenesse: A 16 mg bioresorbable implant is inserted subcutaneously above the anterior supra-iliac crest by a trained healthcare provider every 60 days. For injectable research peptide: Reconstitute with bacteriostatic water. Inject subcutaneously into the abdomen or thigh. Start with 250 mcg daily to assess tolerance, then increase to 500-1000 mcg daily. Rotate injection sites. Administer in the evening to reduce any nausea.
Cycling Protocol
Scenesse implant is administered every 60 days continuously throughout seasons of sun exposure. For injectable melanotan I, a common research protocol is daily injections for 2-3 weeks as a loading phase, then 2-3x/week for maintenance.
Pharmacokinetics
Source: Scenesse FDA Prescribing Information, Section 12.3 Pharmacokinetics. Apparent terminal half-life ~15 hours from 16 mg SC implant.
Loading the interactive decay curve.
Side Effects
Implant site reactions are the most common adverse event, including discoloration (10%), bruising, pain, and swelling. Nausea and headache each affect more than 10% of patients but are typically mild and self-limiting within 1-2 days. Skin darkening is an expected pharmacological effect. Other reported effects include fatigue, dizziness, back pain, and darkening of pre-existing moles and freckles. Allergic reactions including anaphylaxis are rare but possible.
Contraindications
- Pregnancy — no adequate human safety data; discontinue if pregnancy occurs
- Known hypersensitivity to afamelanotide or any component of the implant formulation
- Severe hepatic impairment — afamelanotide may undergo hepatic hydrolysis
- Personal history of melanoma or dysplastic nevi — melanocortin activation could theoretically promote melanocyte proliferation
- Breastfeeding — unknown whether afamelanotide is excreted in human milk
- Children and adolescents — safety and efficacy not established under 18
Drug Interactions
- No formal drug-drug interaction studies have been conducted with afamelanotide
- Anticoagulants (warfarin, heparin, DOACs) — implant insertion involves subcutaneous procedure; increased bleeding risk at insertion site
- Photosensitizing drugs (tetracyclines, fluoroquinolones, NSAIDs) — increased sun tolerance may mask early signs of drug-induced photosensitivity
- Other melanocortin receptor agonists (Melanotan II, PT-141) — additive MC1R stimulation could lead to excessive pigmentation
Storage & Stability
Molecular Profile
Related Peptides
References
- Afamelanotide for Erythropoietic Protoporphyria — Phase 3 EU/US Trials (Langendonk et al., NEJM 2015)PubMed 26132941
- SCENESSE (Afamelanotide) FDA Prescribing InformationFDA Label
- Afamelanotide for Treatment of the Protoporphyrias: Impact on QoL in a US Cohort (Balwani et al., Blood Adv 2024)PubMed 38929673
- Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage in EPP (Biolcati et al., Life 2023)PubMed 37109514
- Phase 3 Trial of Afamelanotide for EPP — US Study (NCT01605136)Clinical Trial