Melanotan I
Melanocortin receptor agonist
A synthetic analog of α-MSH studied in melanogenesis research, the earlier-generation counterpart to Melanotan II.
Also referenced as: MT-1, Melanotan-1, Afamelanotide
Overview
Melanotan I is a synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH), developed at the University of Arizona in the 1980s. Its clinically developed form, afamelanotide, is marketed as Scenesse.
At a glance
What Melanotan I does
Melanotan I — known clinically as afamelanotide (brand Scenesse) — is a synthetic linear analog of α-MSH and is the only melanotropic peptide with regulatory approval, cleared by the EMA (2014) and FDA (2019) as a subcutaneous slow-release implant to prevent phototoxicity in adults with erythropoietic protoporphyria (EPP). Its core action is stimulating melanin production, but unlike the non-selective Melanotan II it is a selective MC1R agonist, with minimal activity at MC3R/MC4R/MC5R — giving it a cleaner profile without the pronounced sexual, appetite and nausea effects of MT-II.
Mechanistically, afamelanotide binds MC1R on melanocytes and, via a cAMP-mediated cascade, upregulates tyrosinase and shifts pigment synthesis toward eumelanin — the dark, photoprotective pigment that absorbs UV and scavenges free radicals — rather than the reddish pheomelanin. Sustained MC1R activation prolongs this eumelanin bias. Importantly, its photoprotection is not purely pigment-based: MC1R signaling also enhances nucleotide-excision repair of UV-induced DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts), boosts antioxidant defenses and modulates inflammation, effects that operate partly independently of visible tanning.
The evidence here is the strongest of any melanocortin peptide: randomized clinical trials in EPP patients demonstrated meaningful photoprotection, with pigmentation developing within roughly 10–14 days of implant and effects lasting on the order of 60–90 days. Outside its approved EPP indication, it is used off-label/in the research market as an injectable tanning agent; it is subcutaneous, not topical.
Effects reported in research
- Selectively activates MC1R on melanocytes, stimulating melanin synthesis and producing UV-independent skin darkening (human clinical data).
- Shifts pigment production toward photoprotective eumelanin over pheomelanin via sustained MC1R/cAMP signaling.
- Enhances nucleotide-excision DNA repair of UV-induced lesions (CPDs and 6-4 photoproducts), independent of pigmentation.
- Provided clinically meaningful photoprotection in randomized trials of erythropoietic protoporphyria (EPP) patients.
- Reduced phototoxic reactions and increased pain-free sun-exposure time in EPP — the basis for FDA/EMA approval.
- Induces antioxidant defenses and modulates cutaneous inflammation via MC1R signaling.
- Much more receptor-selective than Melanotan II, so it largely avoids MT-II's sexual, appetite-suppressing and nausea effects.
- Administered as a subcutaneous slow-release implant/injection (not topical); pigmentation onset ~10–14 days, lasting ~60–90 days.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
Melanotan I is a superpotent, more metabolically stable analog of alpha-MSH that acts as an agonist at melanocortin receptors, with high activity at MC1R. Activation of MC1R on melanocytes stimulates the cAMP pathway, increasing production of eumelanin (melanogenesis) and skin pigmentation. Compared with native alpha-MSH, the substitutions (including Nle and D-Phe) confer greater resistance to enzymatic degradation and longer duration of action.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which Melanotan I appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- Synthetic linear analog of alpha-MSH (13 amino acids).
- Its developed form, afamelanotide, is approved as Scenesse for erythropoietic protoporphyria.
- Selective potency at MC1R drives eumelanin synthesis and pigmentation.
- Distinct from Melanotan II, which is a cyclic heptapeptide with broader melanocortin (including MC4R) activity.
- Structural modifications increase stability versus native alpha-MSH.
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. Melanotan I is a research compound.
Melanotan I is documented both as a research peptide (subcutaneous, weight-based in older studies) and as an approved controlled-release implant (afamelanotide/Scenesse). These are reference figures for research context only, not human dosing guidance.
- Research reference (older human PK studies): ~0.16 mg/kg subcutaneous over a course of weeks
- Approved-product reference: Scenesse 16 mg implant placed subcutaneously approximately every 2 months
Short plasma half-life for the free peptide (~1 h beta-phase) contrasts with the depot implant (apparent half-life ~15 h); pigmentation effect long outlasts plasma presence.
How it compares
Unlike Melanotan II, Melanotan I (afamelanotide) is a linear alpha-MSH analog with an approved clinical form (Scenesse) and comparatively MC1R-focused pigmentation activity.
Commonly studied alongside
Compounds frequently researched together with Melanotan I in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Handling & Stability
Lyophilized peptides are stored cold, protected from light, and reconstituted only at the time of intended in-vitro work.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
Melanotan I sits in the Cosmetic & Dermal area of the PeptiDex library.
- Entry type: Research compound reference
- Browse the full library →
- Glossary of terms →
Where researchers source Melanotan I
For researchers studying Melanotan I, third-party suppliers such as Practically Natty Peptides offer research-grade material with third-party Certificates of Analysis and US-based shipping.
Multiple supplier listings exist for this compound (e.g., dosage variants). The primary research-supplier listing is linked below.
View research-supplier listing →
Outbound link to a third-party research supplier. Inclusion does not constitute endorsement; all editorial content is developed independently.
Frequently asked questions
What is Melanotan I?
Melanotan I is the peptide Nle4-D-Phe7-alpha-MSH, a 13-amino-acid linear analog of alpha-melanocyte-stimulating hormone. It is the same molecule as afamelanotide, and it acts as a melanocortin-1-receptor agonist that stimulates melanin production.
How does Melanotan I relate to afamelanotide and Scenesse?
They are the same active molecule. Afamelanotide is the pharmaceutical name, and Scenesse is the FDA-approved controlled-release subcutaneous implant form (approved in 2019) used to increase pain-free light exposure in adults with erythropoietic protoporphyria (EPP). The research-peptide term 'Melanotan I' refers to the same compound outside that approved implant.
How does Melanotan I differ from Melanotan II?
Melanotan I is a longer, linear 13-residue alpha-MSH analog that is relatively MC1R-focused, while Melanotan II is a smaller cyclic heptapeptide that is broadly non-selective across melanocortin receptors. The narrower activity of Melanotan I is associated with fewer of the off-target effects (like libido changes) seen with MT-II.
What is the half-life of Melanotan I?
For the peptide itself, reported subcutaneous plasma half-lives are short (beta-phase roughly 0.8-1.7 hours in human PK work). The approved Scenesse implant behaves very differently: as a controlled-release depot it shows an apparent half-life around 15 hours with a median Tmax near 36 hours.
What is the sequence and molecular weight of Melanotan I?
The sequence is Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, with a molecular weight of about 1646.9 Da. The norleucine-for-methionine and D-Phe-for-L-Phe substitutions increase resistance to enzymatic degradation versus native alpha-MSH.
How is Melanotan I administered in research?
Research literature describes subcutaneous administration; older human studies referenced dosing on the order of ~0.16 mg/kg over a course of weeks. The approved product instead uses a subcutaneous implant placed roughly every two months.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.