Melanotan 1 – Product Description

The Original α-MSH Analog for Photoprotection and Pigmentation Research

Melanotan 1 (MT-I), also known as afamelanotide, is a synthetic analog of the naturally occurring α-melanocyte-stimulating hormone (α-MSH) . As a potent, non-selective melanocortin receptor (MCR) agonist, it stimulates melanocytes to increase melanin production, providing a protective effect against ultraviolet radiation (UVR)-induced skin damage . This synthetic peptide is one of the foundational compounds in pigmentation research and has been clinically developed as a photoprotective agent for conditions like erythropoietic protoporphyria (EPP) .

Table of Contents

1. What is Melanotan 1?

2. Mechanism of Action

3. Key Research Findings

4. Dosing and Administration

5. Safety Profile

6. Frequently Asked Questions (FAQs)

7. References

What is Melanotan 1?

Melanotan 1 is a synthetic 13-amino acid peptide analog of α-MSH with the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂ . It incorporates two key modifications from the native hormone: norleucine substitution at position 4 and D-phenylalanine at position 7, which enhance its potency and stability .

Mechanism of Action

Melanotan 1 functions primarily through agonism of the melanocortin 1 receptor (MC1-R) on melanocytes :

The active site responsible for melanocortin activity is the conserved sequence His-Phe-Arg-Trp, which is shared with the endogenous hormone and other melanocortin peptides .

Key Research Findings

Clinical Safety and Efficacy (Phase 1)

Three phase 1 clinical trials demonstrated that Melanotan 1 can be safely combined with UV-B light or sunlight and acts synergistically in the tanning response :

• 10-day trial (0.08 mg/kg): 3 of 4 subjects achieved tanning with 47% fewer sunburn cells at irradiated sites

• Higher dose (0.16 mg/kg): More skin sites darkened with enhanced effect

• Sunlight study: MT-I group showed significantly enhanced tanning maintained at least 3 weeks longer than controls, who required 50% more sun-exposure time for equivalent tanning

• Toxic effects: Minor, consisting of nausea and transient facial flushing

Sustained Pigmentation

Controlled-release implants containing 4 mg Melanotan 1 demonstrated prolonged skin darkening for up to three months in animal models, with a 2.5-fold increase in eumelanin levels observed after one month .

FDA-Approved Indication

Afamelanotide (Melanotan 1) is FDA-approved as SCENESSE for increasing pain-free light exposure in adult patients with erythropoietic protoporphyria (EPP), a condition causing severe phototoxic reactions . It is administered as a 16 mg subcutaneous implant every 2 months .

Dosing and Administration

Storage Guidelines — Lyophilized peptide should be stored in a freezer at or below -20°C. Reconstituted solution can be stored at -20°C for up to six months .

Safety Profile

Melanotan 1 is generally well-tolerated in clinical research settings, with adverse effects typically being mild .

Common Adverse Reactions

• Nausea (most frequently reported) 

• Transient facial flushing 

• Implant site reaction (for SCENESSE) 

• Skin hyperpigmentation (expected pharmacological effect) 

• Fatigue, dizziness, somnolence (SCENESSE) 

Important Safety Considerations

• Skin Monitoring: Regular full-body skin examinations are recommended due to potential darkening of pre-existing nevi and ephelides 

• Hypersensitivity: Serious reactions including anaphylaxis have been reported; SCENESSE is contraindicated in patients with known hypersensitivity 

• Dysplastic Nevi: Melanotan I has been associated with activation of dysplastic nevi 

Frequently Asked Questions (FAQs)

1. What is the difference between Melanotan 1 and Melanotan 2?

Melanotan 1 (afamelanotide) is primarily a photoprotective agent that stimulates melanin production. Melanotan 2 is a cyclic analog that also affects melanocortin receptors but has additional effects, including on erectile function . They have distinct amino acid sequences and receptor binding profiles.

2. Is Melanotan 1 FDA-approved?

Yes. Afamelanotide (Melanotan 1) is FDA-approved as SCENESSE for the treatment of erythropoietic protoporphyria (EPP) . It is not approved for cosmetic tanning purposes.

3. What is the mechanism of action?

Melanotan 1 binds to melanocortin 1 receptors (MC1-R) on melanocytes, mimicking the action of endogenous α-MSH. This stimulates the production and release of melanin, which provides photoprotection against UV radiation .

4. How is Melanotan 1 administered?

In clinical research, it is typically administered via subcutaneous injection daily for a defined period. The FDA-approved formulation (SCENESSE) is a subcutaneous implant containing 16 mg of afamelanotide, administered every 2 months by a healthcare professional .

5. What are the side effects?

Common side effects include nausea, transient facial flushing, and injection/implant site reactions . Skin hyperpigmentation is an expected effect. Regular skin monitoring is recommended due to the potential for darkening of existing moles .

6. Does Melanotan 1 have antioxidant properties?

Yes. By increasing melanin production, it may protect against UVR-initiated cellular DNA damage and oxidation of membrane proteins . However, it is not studied as a systemic antioxidant.

7. Is Melanotan 1 used for male erectile dysfunction research?

While Melanotan 1 has been noted in research related to melanoma and male erectile dysfunction , this is more prominently associated with Melanotan 2, which has been studied for its effects on penile erection via central and peripheral melanocortin pathways .

References

1. DrugFuture. Melanotan – CAS Registry Information 

2. BioPortal / NCI Thesaurus. Afamelanotide (Melanotan I) – Definition and Properties 

3. FDA DailyMed. SCENESSE (afamelanotide) – Prescribing Information. 2024 

4. NovoPro Bioscience. Melanotan I Peptide – Product Specifications 

5. TargetMol. Melanotan I – Product Information 

6. PubMed. Phase 1 Clinical Trials of Melanotan-1. J Invest Dermatol. 2005 

7. BOC Sciences. Melanotan I – Product Information and References 

8. PubMed. Pharmacologic Response of Controlled-Release PLGA Formulation for Melanotan-I. Pharm Res. 2000