MT-1


Melanotan I is a linear peptide that primarily binds with high affinity and selectivity to the Melanocortin 1 Receptor (MC1R). This receptor is found on melanocytes, which are the skin pigment cells. This interaction stimulates the production of eumelanin, the dark pigment in the skin. The increase in eumelanin provides enhanced photoprotection against ultraviolet (UV) radiation.

MT-1 OVERVIEW

Category: Synthetic Tridecapeptide, Melanocortin Receptor Agonist

 

How It Works: Melanotan I is a linear peptide that primarily binds with high affinity and selectivity to the Melanocortin 1 Receptor (MC1R). This receptor is found on melanocytes, which are the skin pigment cells.

Chemical Structure: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (13 AAs)

Alternative Names: Scenesse, Melanotan 1, Afamelanotide

 

CAS Number: 75921-69-6

WHAT IS MT-1

The MT-1 peptide, officially known as Afamelanotide, is a synthetic analog of the naturally occurring alpha-melanocyte-stimulating hormone (alpha-MSH). It is a synthetic tridecapeptide (composed of 13 amino acids). Melanotan I was engineered to overcome the extremely short half-life of natural alpha-MSH and maximize its effect on skin pigmentation.

WHAT DOES MT-1 DO?

Melanotan I primarily functions as an agonist of the Melanocortin 1 Receptor (MC1R), which is predominantly expressed on skin cells (melanocytes). This hormone-like action is the basis for both its approved medical use and its cosmetic effects.

Mechanism of Action

  • Melanogenesis Stimulation: Activation of MC1R stimulates the synthesis and release of eumelanin (the protective, dark pigment, typically black/brown), as opposed to pheomelanin (the red/yellow pigment).

  • Gene Activation: MC1R activation initiates a signaling cascade (cAMP production $\rightarrow$ MITF expression) that induces the enzymes (tyrosinase) necessary for eumelanin production.

 Key Effects and Benefits

  • Photoprotection: Eumelanin offers superior protection against UV radiation by absorbing and scattering light and neutralizing free radicals. By artificially inducing a deep tan, MT-1 provides internal photoprotection, reducing UV-initiated DNA damage and oxidative stress in epidermal cells. This is the rationale behind its FDA-approved use.

  • Self-Tanning: MT-1 plays a prominent role in the production of pigment in the skin, allowing for self-tanning with lower UV exposure. This means that the body will grow tanned all over, even in places that are not exposed to sunlight. However, UV exposure will accelerate the tanning process in exposed areas.

  • Other MCR Effects: Like other alpha-MSH analogs, MT-1 is a non-selective agonist that interacts with other melanocortin receptors (MC3R, MC4R). It may also help to reduce sun damage and has been anecdotally associated with increasing sexual arousal, sexual desire, and appetite.

BENEFITS/ CLINICAL TRIALS

Melanotan I is a linear peptide that primarily binds with high affinity and selectivity to the Melanocortin 1 Receptor (MC1R) found on melanocytes (skin pigment cells).  This interaction stimulates the production of eumelanin, a dark pigment that provides photoprotection against ultraviolet (UV) radiation. The primary development and approved use for MT-1 centers on its therapeutic photoprotective effects.

 Key Benefits Observed in Clinical Trials
  •  Treatment of Erythropoietic Protoporphyria (EPP): MT-1 (Afamelanotide) is FDA-approved for use in patients with EPP, a rare genetic disorder that causes extreme photosensitivity, leading to severe pain and skin damage upon light exposure.  The induced eumelanin helps these patients tolerate light exposure.  

  • Skin Pigmentation: Successfully induces significant and long-lasting skin darkening (tanning) following subcutaneous administration, peaking about a week after treatment completion.

  • Photoprotection: In controlled clinical studies, MT-1 has been shown to:

    • Enhance the skin's natural defense mechanisms against UV damage.  

    • Help achieve a tan with less UV exposure compared to controls. 

    • Reduce UV-induced cellular damage (sunburn cells). 

  • Photodamage Reduction: Trials have investigated its role in protecting against non-melanoma skin cancer and photoinduced skin diseases.

  • Enhanced Stability: It also has a longer half-life than the natural hormone it mimics (alpha-MSH).

 

SIDE EFFECTS

 

Melanotan I (Afamelanotide) has a more favorable side effect profile than the highly non-selective Melanotan II (MT-2), but users must be aware of potential reactions, particularly related to skin changes.

 

Common and Systemic Side Effects

  • Dermal/Pigmentation: General skin darkening (tanning), and crucially, the darkening and potential change in shape or size of pre-existing moles (nevi). The appearance of new moles (hyperpigmentation) may also occur.

    • Precaution: A twice-yearly full body skin examination is recommended for patients using the approved brand Scenesse, as there is an ongoing concern that increased melanocyte proliferation may elevate the risk of atypical moles or melanoma in susceptible individuals.

  • Gastrointestinal (GI): Nausea and abdominal pain, or mild GI upset.

  • Neurological: Headache, dizziness, fatigue, and somnolence (sleepiness/drowsiness), or temporary tiredness/yawning following injection.

  • Other Systemic: Flushing (a temporary redness or warmth of the skin), cough, sore throat, or respiratory tract infections.

  • Behavioral: Changes in appetite (decreased) have been reported.

 Local Reactions

  • Implant or Injection Site Reactions: Pain, redness, bruising, swelling, or itching at the site where the implant or injection was placed.

IS MT-1 SAFE?

Melanotan I (Afamelanotide) is an FDA-approved drug for the specific indication of Erythropoietic Protoporphyria (EPP).

 

Comparative Effects and Side Effects

  • Milder Action: Melanotan I is generally considered to be milder than Melanotan II (MT-2). Studies have shown that Melanotan I can take much longer to develop a tanning effect than MT-2.

  •  Common Side Effects: Other common side effects include facial flushing, nausea, and new or darkened freckles. 

     
    Safety Takeaway
  • Approved Use: When used under medical supervision for EPP treatment, the benefits of MT-1 outweigh the risks.

  • Unsupervised Cosmetic Use (CRITICAL WARNING): Its use as an unsupervised cosmetic tanning agent is highly discouraged by health authorities (FDA, TGA, HPRA) due to the unknown long-term risk of melanocytic proliferation and the development of new or atypical moles.

  • Illegal Formulations: Oral or nasal spray formulations sold online are illegal and have minimal bioavailability (meaning they are ineffective for the intended purpose).

DOSAGE

Dosing for Melanotan I is highly dependent on the therapeutic goal (FDA-approved photoprotection versus cosmetic research).

 

Administration Methods

  • Approved Use (EPP): Administered via a subcutaneous implant that releases the drug slowly over 60 days for sustained photoprotection.

  • Research Injectable: Typically administered via subcutaneous (SubQ) injection.

  • Half-Life: The free peptide has a short half-life (approximately 1 to 2 hours), which is why implant technology was developed for a sustained therapeutic effect in approved applications.

 

Example Dosing Protocols (SubQ Injection) 

These protocols reflect practices seen in research or off-label use, where doses are generally microgram-level (e.g., 0.5 mg to 1.0 mg) several times per week in early cosmetic research.

  • Protective Dose (Acute): 0.25 mg (0.05 ml or 5 units) injected subcutaneously (SQ) 30 minutes before sun exposure.

  • Maintenance Dose (Building Pigment): 0.25 mg (0.05 ml or 5 units) to 0.5 mg (0.1 ml or 10 units) injected subcutaneously (SQ) daily for 10 days.

  • Ongoing Maintenance: After the initial period, continue injecting 1 to 2 times per week to maintain pigmentation.

  • Note on Side Effects: If you experience intolerable side effects at any stage, try a lower dose.

RECONSTITUTION

MT-1 is supplied as a lyophilized (freeze-dried) powder for injection use in the research market.

 

Reconstitution Fluid and Dilution 

  • Reconstitution Fluid: Use sterile or bacteriostatic water (BAC Water) or saline.

  • Draw Volume: For certain protocols, inject 2 mL of bacteriostatic water into the vial of powder. You will need to inject 2 full 1 mL syringes of water into the vial (2 mL equals 200 units on a standard insulin syringe).

  • Standard Dilution (EX: 10 mg Vial): For a 10 mg vial, adding 1 mL of BAC water results in a highly concentrated solution of 10 mg/mL.

 

Mixing Technique

  • Inject Diluent: Inject the BAC Water slowly down the side of the vial.

  • Mixing: DO NOT SHAKE vigorously. Gently swirl the vial until the powder is completely dissolved into a clear solution.

 

Post-Reconstitution Storage

  • Storage: Once reconstituted, the solution must be stored in the refrigerator (2°C to 8°C).

  • Stability: The solution is typically stable for 14 to 28 days under proper refrigeration.

Step by step guidelines

WHERE TO BUY MT-1

Researchers should always vet their sources to ensure that a few key factors are present in their test subjects. With the rise in peptide popularity in recent years, many companies have created peptides that undergo little to no testing, quality standards, or regulations. As it is not regulated by the FDA, researchers must do their due diligence and look closely at the company's practices and standards. 

When selecting a supplier for MT-1, focus on transparency and quality assurance, not customer testimonials:

  1. Quality Documentation: A reputable supplier must provide:
    •  Certificate of Analysis (COA): This document must be recent (corresponding to the batch/lot number purchased) and demonstrate a minimum purity of >95% via High-Performance Liquid Chromatography (HPLC) testing.
    • Mass Spectrometry (MS) Data: The COA must include mass spectrometry (MS) confirmation to verify the compound’s exact molecular weight, confirming its chemical identity.
    • Contaminant Testing: Look for reports on heavy metals, microbial load, and solvent residues (e.g., residual trifluoroacetic acid, or TFA). The presence of these contaminants can severely compromise research and introduce unknown toxicity.
  2. Vendor Verification and Transparency 
    • Specialization: Prioritize vendors who specialize in the manufacturing and distribution of peptides for academic and biotechnology research, rather than general supplement vendors.

    • Manufacturing Origin: Inquire about the source of the raw materials and the manufacturing protocols. Ideal suppliers adhere to strict quality control processes.

    • Handling & Storage: The supplier must provide clear documentation on the proper storage and handling procedures for the peptide to maintain its stability and integrity.

Conclusion on Procurement: Given the high risk of contamination, mislabeling, and legal ambiguity. The use of MT-1 outside of this defined research context poses unacceptable, unquantified risks to human health.

REFERENCES

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