> Research Use Only Disclaimer: Melanotan I (afamelanotide) is approved as Scenesse® (Clinuvel Pharmaceuticals) for erythropoietic protoporphyria (EPP) in Europe and the US. Outside of this indication, all information in this article is for research purposes only. This compound is not approved for general cosmetic, tanning, or other human use. Not for human use outside of supervised clinical settings. Always comply with local regulations.
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What Is Melanotan I (Afamelanotide)?
Melanotan I — also known by its INN afamelanotide — is a linear synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH), the endogenous peptide produced from the proopiomelanocortin (POMC) precursor. While α-MSH itself is a tridecapeptide, Melanotan I incorporates a key structural modification at position 4: substitution of the native methionine residue with a norleucine (Nle) group, and replacement of the phenylalanine at position 7 with D-phenylalanine (DPhe).
These substitutions dramatically increase receptor binding affinity and metabolic stability compared to native α-MSH, while preserving the linear backbone — a distinction that defines MT-I's pharmacological profile relative to the cyclic Melanotan II.
Molecular formula: C78H111N21O19
Molecular weight: 1646.85 g/mol
Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2
CAS Number: 75921-69-6
FDA Approval Status
Afamelanotide received European Medicines Agency (EMA) approval in 2014 as Scenesse® for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare genetic disorder. It received FDA approval in the United States in October 2019 under the same indication. Scenesse is delivered as a bioresorbable subcutaneous implant (16 mg) by a healthcare provider, distinct from the lyophilized powder used in research settings.
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Melanotan I vs Melanotan II: Why Selectivity Matters in Research
The most important distinction between MT-I and MT-II lies in receptor selectivity — a property with major implications for research applications.
Melanocortin Receptor Subtypes
The melanocortin receptor family comprises five G protein-coupled receptors (MC1R–MC5R), each with distinct tissue distribution and functional roles:
| Receptor | Primary Location | Function |
|---|---|---|
| MC1R | Melanocytes, immune cells | Pigmentation, anti-inflammatory |
| MC2R | Adrenal cortex | Cortisol regulation (ACTH receptor) |
| MC3R | Hypothalamus, limbic system | Energy homeostasis, food intake |
| MC4R | Hypothalamus, CNS | Appetite suppression, sexual function |
| MC5R | Exocrine glands, peripheral tissue | Sebaceous secretion, thermoregulation |
MT-I: Selective MC1R Agonism
Melanotan I demonstrates preferential binding at MC1R with high affinity (Ki approximately 0.1-0.5 nM in competitive radioligand binding studies), while showing substantially reduced activity at MC3R, MC4R, and MC5R. This selectivity is a product of its linear peptide conformation — the open-chain structure doesn't adopt the constrained beta-turn geometry that underlies MT-II's promiscuous multi-receptor engagement.
Key research implication: MT-I's MC1R selectivity means research subjects (animal models) do not exhibit the MC4R-mediated sexual function effects, appetite suppression changes, or MC3R-related metabolic signaling that complicate MT-II research protocols.
MT-II: Broad Melanocortin Agonism
Melanotan II is a cyclic heptapeptide — the cyclization via a lactam bridge creates a constrained beta-turn that enables high-affinity binding across MC1R, MC3R, MC4R, and MC5R. This broad agonism accounts for its additional observed effects in research (sexual arousal signaling via MC4R, appetite suppression via MC3R) but also makes it a more complex tool for isolating pigmentation and photoprotective mechanisms.
Bottom line for researchers: When the research question is specifically about melanogenesis, UV photoprotection, or MC1R-mediated anti-inflammatory pathways — MT-I is the more selective research tool.
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Research Forms and Purity
Melanotan I is commercially available from research peptide suppliers as:
- •Lyophilized (freeze-dried) powder — most common form; stable at room temperature short-term, best stored frozen
- •Typical quantities: 10 mg vials (most common), 5 mg, 20 mg
- •Purity specification: >=98% by HPLC is standard for research-grade material; reputable suppliers provide CoA with MS confirmation and HPLC trace
What to Verify on a Certificate of Analysis (CoA)
When sourcing MT-I for research, request documentation showing:
1. HPLC purity (>=98%)
2. Mass spectrometry confirmation (molecular weight 1646.85 +/- 1 Da)
3. Sterility testing for injectables (if applicable to the research protocol)
4. Endotoxin levels (LAL test) for cell-based or animal studies
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Reconstitution Protocol
Melanotan I powder must be reconstituted into a sterile solution before use in research. Bacteriostatic water (BAC water, 0.9% benzyl alcohol) is the standard diluent for research reconstitution.
Why Bacteriostatic Water?
BAC water contains 0.9% benzyl alcohol, a preservative that inhibits microbial growth and extends the usable life of the reconstituted peptide. Standard sterile water (without preservative) should be used immediately after reconstitution; BAC water-reconstituted peptides can be stored refrigerated and used over a multi-week window.
Reconstitution Steps
1. Remove the vial of lyophilized MT-I powder from storage; allow to reach room temperature (reduce condensation risk)
2. Wipe the rubber stopper with an alcohol swab; allow to dry
3. Using an insulin syringe or sterile syringe with needle, draw the desired volume of BAC water
4. Inject BAC water slowly down the side of the vial (do not spray directly onto the powder)
5. Gently swirl — do not shake — until the powder is fully dissolved; the solution should be clear and colorless
6. Label the vial with date and concentration
Reconstitution Concentration Calculator
The most common research concentrations are 1 mg/mL or 2 mg/mL:
| Vial Size | BAC Water Volume | Final Concentration | Volume per 100 mcg dose |
|---|---|---|---|
| 10 mg | 10 mL | 1 mg/mL (1000 mcg/mL) | 0.10 mL (10 units on insulin syringe) |
| 10 mg | 5 mL | 2 mg/mL (2000 mcg/mL) | 0.05 mL (5 units on insulin syringe) |
| 10 mg | 2 mL | 5 mg/mL (5000 mcg/mL) | 0.02 mL (2 units on insulin syringe) |
Note: Standard U-100 insulin syringes measure in units where 100 units = 1 mL.
For precise dosing calculations, use the Peptides.SO Reconstitution Calculator.
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Research Dosing Ranges from Literature
> Important: The following dosing information is derived from published clinical and preclinical research only. This information is presented for educational and research reference purposes. It does not constitute medical advice or a treatment protocol.
Clinical Research Context: EPP and Photoprotection
The most extensive human research on afamelanotide dosing comes from clinical trials for erythropoietic protoporphyria (EPP). Key published studies:
Harms et al. (2009) — Phase 2 EPP trial:
- •Dose: 16 mg subcutaneous implant (ClinUVel controlled-release formulation)
- •Frequency: Every 60 days
- •Outcome: Statistically significant increase in pain-free sun exposure time
Langendonk et al. (2015) — Phase 3 EPP trial (NEJM):
- •Dose: 16 mg implant
- •Endpoint: Total minutes of sunlight exposure without pain
- •Result: Afamelanotide group: 69.4 min; placebo: 40.8 min (p=0.04)
Grattan et al. (2019) — Phase 3 US trial:
- •Confirmed efficacy at 16 mg implant dose for photoprotection in EPP
Research Dosing in Animal Models
In murine and porcine photoprotection models, MT-I has been administered at:
- •0.1-1.0 mg/kg subcutaneous (single dose, melanogenesis studies)
- •10-100 mcg/kg in UV-mediated melanocyte proliferation studies
- •Frequency: Every 48-72 hours in repeated-dose protocols
These ranges are from preclinical literature and represent the parameters used in published laboratory research, not human dosing recommendations.
Pigmentation Research Ranges
In published human pilot studies examining MT-I for cosmetic photoprotection (prior to its EPP focus), doses of 0.5-1.0 mg administered subcutaneously were investigated. These studies (primarily from Hadley et al. at the University of Arizona, 1990s-2000s) documented dose-dependent increases in skin pigmentation measured by reflectance spectrophotometry.
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Administration Route
In research settings and in the FDA-approved clinical application, Melanotan I is administered subcutaneously. The Scenesse clinical formulation uses a bioresorbable implant placed subdermally by a healthcare provider.
In preclinical research, subcutaneous injection (SC) is standard protocol. Intravenous and intraperitoneal routes have been explored in animal models for pharmacokinetic studies.
MT-I is not formulated for intranasal administration (unlike Semax or Selank). The large molecular weight (1646.85 g/mol) makes nasal mucosa absorption impractical without chemical modification or permeation enhancers.
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Photoprotection Research Context
Mechanism in UV Photoprotection
MT-I's photoprotective effect operates through a dual mechanism:
1. Melanogenesis activation: MC1R agonism activates adenylyl cyclase, elevating cAMP, which activates PKA, which phosphorylates and activates MITF (microphthalmia-associated transcription factor), upregulating tyrosinase, TRP-1, and TRP-2, driving eumelanin synthesis. Eumelanin (brown/black pigment) is the primary photoprotective melanin species.
2. DNA repair upregulation: Independent of pigmentation, MC1R signaling has been shown to upregulate nucleotide excision repair (NER) pathways and reduce UV-induced apoptosis in melanocytes. Research by Bohm et al. demonstrated that alpha-MSH/MC1R signaling reduces UV-induced cyclobutane pyrimidine dimer (CPD) formation markers.
Erythropoietic Protoporphyria (EPP)
EPP is caused by a loss-of-function mutation in the ferrochelatase (FECH) gene, leading to accumulation of protoporphyrin IX in red blood cells, skin, and liver. Protoporphyrin IX is photoactivated by visible light (400-420 nm, Soret band), causing painful photosensitivity reactions. Because EPP photosensitivity is triggered by visible light (not UV), conventional sunscreens are ineffective — afamelanotide's melanogenesis-based photoprotection provides mechanistically relevant benefit.
Solar Urticaria and Other Research Applications
Beyond EPP, published research has explored MT-I in:
- •Solar urticaria — photoallergic urticarial response to UV/visible light
- •Polymorphous light eruption (PMLE) — immune-mediated photosensitivity
- •Vitiligo — repigmentation in combination with NB-UVB phototherapy (pilot data)
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Side Effect Profile vs Melanotan II
MC1R selectivity gives MT-I a cleaner side effect profile in research compared to MT-II:
| Effect | Melanotan I (MT-I) | Melanotan II (MT-II) |
|---|---|---|
| Nausea | Mild, transient | Moderate to significant |
| Facial flushing | Mild | Common |
| Sexual arousal effects | Not observed (no MC4R) | Reported (MC4R agonism) |
| Appetite suppression | Minimal | Common (MC3R/MC4R) |
| Yawning/stretch reflex | Not observed | Common |
| Spontaneous erections (male models) | Not reported | Documented |
| Hyperpigmentation (nevi) | Observed in clinical trials | Observed |
In the Scenesse clinical trial program, the most commonly reported adverse events were:
- •Nausea (13-22% of subjects)
- •Fatigue
- •Injection site reactions
- •Hyperpigmentation of existing nevi (moles)
The absence of MC4R-mediated effects makes MT-I significantly less confounding for pure melanogenesis or photoprotection research.
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Storage and Stability
Lyophilized Powder (Unreconstituted)
- •Short-term (<=3 months): Refrigerator (2-8 degrees C), away from light
- •Long-term (>3 months): Freezer (-20 degrees C or below); minimize freeze-thaw cycles
- •Light sensitivity: Protect from UV light; amber vials recommended
- •Humidity: Store in a desiccated environment; silica gel packets in storage container
Reconstituted Solution (BAC Water)
- •Refrigerator (2-8 degrees C): Stable for 4-6 weeks with BAC water as diluent
- •Freezer (-20 degrees C): Can extend to 3-6 months, but aliquot before freezing to avoid repeated freeze-thaw cycles
- •Do not freeze if the vial contains a BAC water solution you plan to use repeatedly — refrigeration is preferred for active use
Degradation Indicators
A reconstituted MT-I solution should be clear and colorless. Discard if:
- •Solution becomes cloudy or particulate
- •Color changes (yellowing may indicate oxidation)
- •Any precipitation is observed
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Internal Research Resources
For researchers working with the melanocortin system, the following Peptides.SO resources provide complementary reference material:
- •Melanotan I vs Melanotan II: Research Comparison Guide — Receptor selectivity deep-dive, side-by-side pharmacology comparison
- •Melanotan II Research Profile — Cyclic MT-II pharmacology, MC4R agonism mechanisms
- •Alpha-MSH Research Profile — The endogenous parent peptide
- •Setmelanotide (MC4R Selective) Research — The MC4R-selective comparator compound
- •Peptide Reconstitution Calculator — Calculate exact BAC water volumes and concentrations
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Key Research Citations
1. Langendonk JG, et al. "Afamelanotide for Erythropoietic Protoporphyria." N Engl J Med. 2015;373(1):48-59. PMID: 26132941
2. Harms J, et al. "An alpha-melanocyte stimulating hormone analogue in erythropoietic protoporphyria." Br J Dermatol. 2009;160(2):382-387. PMID unverified
3. Hadley ME, Dorr RT. "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization." Peptides. 2006;27(4):921-930. PMID: 16412534
4. Bohm M, et al. "Alpha-melanocyte-stimulating hormone modulates activation of NF-kappa B and AP-1 and secretion of interleukin-8 in human dermal fibroblasts." Ann N Y Acad Sci. 1999;885:277-286. PMID: 10816661
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Summary
Melanotan I (afamelanotide) is the most clinically validated peptide in the melanocortin research toolkit — the only MC1R agonist to achieve FDA approval (Scenesse® for EPP, 2019). Its linear structure confers MC1R selectivity, distinguishing it from the cyclic MT-II and making it a cleaner research tool for pigmentation and photoprotection studies unconfounded by MC3R/MC4R signaling.
For researchers working with lyophilized MT-I, reconstitution with bacteriostatic water at 1-2 mg/mL is standard practice. Published research dosing in preclinical models ranges from 0.1-1.0 mg/kg SC; the clinical EPP data used 16 mg controlled-release implants at 60-day intervals.
With 65+ suppliers carrying MT-I on Peptides.SO, it represents the highest-supply-density compound on the platform — and its FDA-approved clinical analog status makes it one of the most extensively studied melanocortin peptides in the scientific literature.
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For Research Use Only. This article is provided for educational and research reference purposes. Melanotan I/afamelanotide outside of the FDA-approved Scenesse indication is not approved for human use. Always comply with applicable laws and institutional regulations.
> Citation correction (2026-08-09): One or more PMID references in this article were verified against NCBI PubMed and found to resolve to unrelated papers. The affected citations have been updated below. Trial names and research claims are retained where independently supported by published literature; specific PMIDs have been removed pending editorial re-verification.