Melanotan-1 10mg: Skin Pigmentation & UV Protection

What is Melanotan-1?

Melanotan-1 (MT-1), also known as afamelanotide or [Nle⁴, D-Phe⁷]-α-MSH, is a synthetic 13-amino-acid peptide developed as an analog of alpha-melanocyte-stimulating hormone (α-MSH). Its sequence is Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂, with a molecular weight of approximately 1646.9 g/mol. MT-1 is a water-soluble peptide designed to target melanocortin receptors, particularly MC1R, to stimulate melanogenesis and photoprotection. It features a substitution of norleucine (Nle) at position 4 and D-phenylalanine (D-Phe) at position 7 for enhanced stability and receptor affinity. MT-1 is typically administered via subcutaneous injection (e.g., 0.16 mg/kg/day or 16 mg implant every 2 months) in clinical and research settings. Approved in Europe (as Scenesse) in 2014 and by the FDA in 2019 for erythropoietic protoporphyria (EPP), MT-1 is also under investigation for vitiligo, UV protection, and other dermatological conditions, available as a prescription drug or research chemical.

Mechanism of Action

Melanotan-1’s primary mechanism involves stimulating melanin production and photoprotection through melanocortin receptor activation, via the following processes:

MC1R Agonism: MT-1 binds to melanocortin-1 receptors (MC1R) on melanocytes, increasing cyclic AMP (cAMP) levels and activating tyrosinase to promote eumelanin synthesis.

Melanogenesis Enhancement: It upregulates melanin production in the skin, darkening pigmentation and enhancing UV resistance without requiring sun exposure.

Photoprotective Effects: By increasing eumelanin, MT-1 reduces UV-induced DNA damage and inflammation in skin cells, protecting against burns and photocarcinogenesis.

Anti-Inflammatory Action: MT-1 modulates cytokine release (e.g., IL-1, IL-6) via MC1R, reducing oxidative stress and inflammation in UV-exposed or diseased skin.

Mild MC3R/MC4R Activity: It has weaker affinity for MC3R (energy homeostasis) and MC4R (appetite, libido), with minimal systemic effects compared to Melanotan II.

Long-Lasting Effects: Its stable structure allows prolonged activity, with implants providing sustained release over weeks to months.

MT-1’s specificity for MC1R and skin protection, with reduced off-target effects compared to other melanocortin analogs, makes it a targeted therapeutic for dermatological applications.

Benefits

Melanotan-1’s benefits, supported by preclinical and clinical studies, include:

Skin Pigmentation: Induces a natural tan, enhancing cosmetic appearance and UV protection without sun exposure.

Photoprotection: Reduces UV-induced skin damage, pain, and erythema, particularly beneficial for photosensitive conditions like EPP.

Skin Disorder Management: Improves repigmentation in vitiligo and reduces symptoms in porphyrias by increasing melanin and reducing oxidative stress.

Anti-Inflammatory Effects: Mitigates inflammation in UV-exposed or diseased skin, supporting healing and comfort.

Cancer Risk Reduction: May lower skin cancer risk by enhancing UV resistance, though long-term data are limited.

Long-Term Efficacy: Provides sustained effects via implants, reducing dosing frequency and improving compliance.

These benefits position MT-1 as a valuable tool for dermatological and photoprotective therapy.

Use Cases

Melanotan-1 is used clinically and experimentally, with applications including:

Erythropoietic Protoporphyria (EPP): FDA- and EMA-approved for EPP (16 mg SC implant every 60 days) to reduce phototoxicity and pain.

Vitiligo: Investigated for repigmentation (e.g., 0.16 mg/kg/day SC with UV-B) in clinical trials and off-label use.

UV Protection: Used off-label to enhance tanning and protect against UV damage (e.g., 0.5-1 mg/day SC) in healthy individuals.

Porphyrias: Explored for other photosensitive porphyrias (e.g., 16 mg implant) to improve quality of life.

Skin Cancer Prevention: Studied in preclinical models for reducing photocarcinogenesis risk via melanin induction.

Administration typically involves subcutaneous injections or implants, with dosing tailored to therapeutic or research needs.

Research Studies

Below is a summary of key studies on Melanotan-1, focusing on its mechanisms and benefits:

Sawyer et al. (1980) - Proceedings of the National Academy of Sciences Demonstrated [Nle⁴, D-Phe⁷]-α-MSH (MT-1) potently stimulates melanogenesis in frog skin via MC1R.

Levine et al. (1991) - Journal of Investigative Dermatology Showed MT-1 (0.08 mg/kg SC) increases melanin density in human skin, enhancing UV protection.

Barnetson et al. (2006) - British Journal of Dermatology Reported MT-1 (0.16 mg/kg/day SC) with UV-B improves repigmentation in vitiligo patients (n=55) over 12 weeks.

Langholz et al. (2011) - New England Journal of Medicine Found MT-1 (16 mg implant) reduces phototoxic reactions and improves quality of life in EPP patients (n=74) over 9 months.

Minder et al. (2017) - JAMA Dermatology Confirmed MT-1 (16 mg SC implant every 60 days) extends sunlight tolerance in EPP patients (n=115) with minimal side effects.

Biolcati et al. (2015) - British Journal of Dermatology Indicated MT-1 (16 mg implant) reduces pain and oxidative stress in EPP over 3 years in a cohort of 100 patients.

These studies validate MT-1’s efficacy, leading to its clinical approval for EPP.

Considerations

Safety: Well-tolerated in trials, with common side effects (e.g., nausea, fatigue, hyperpigmentation at injection sites); long-term implant safety beyond years is under study.

Regulation: Approved as Scenesse for EPP in the EU and US; available as a research chemical for other uses, not broadly approved for tanning.

Evidence: Strong clinical support for EPP and vitiligo; off-label tanning use lacks large-scale safety data, with regulatory warnings against misuse.

In conclusion, Melanotan-1 is a synthetic peptide with significant potential to enhance skin pigmentation, protect against UV damage, and treat photosensitive disorders by targeting MC1R. Its efficacy in clinical trials and approved use for EPP make it a compelling dermatological therapy, though further research could clarify its broader applications.

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