Melanotan 1 (10mg)

Melanotan 1 Research

Melanotan-1 (afamelanotide or NDP-MSH) was developed as a potential therapeutic agent for photoprotection and has been studied for various dermatological applications.

The peptide was initially developed by researchers at the University of Arizona in the 1980s. It works by activating melanocortin receptors, particularly the melanocortin 1 receptor (MC1R) found in melanocytes, which stimulates melanin production. Increased melanin production provides enhanced protection against UV radiation damage.

Key areas of Melanotan-1 research include:

1. Photoprotection for individuals with photosensitivity disorders
2. Treatment of erythropoietic protoporphyria (EPP)
3. Potential applications for vitiligo and other pigmentation disorders
4. Mechanisms of melanogenesis and melanocortin receptor signaling

Melanotan 1 and Photoprotection

Melanotan 1 works by binding to the MC1R receptor on melanocytes, stimulating the production of eumelanin, which provides a natural form of photoprotection by absorbing UV radiation and reducing DNA damage. This process enhances the skin’s ability to repair UV-induced DNA photoproducts and reduces apoptosis in melanocytes,  potentially lowering the risk of skin cancer¹.

Clinical studies have demonstrated that Melanotan significantly increases melanin density in the skin, offering enhanced protection against UV-induced damage, particularly in individuals with lighter skin types who are more susceptible to sunburn and skin cancer. Trials have shown that Melanotan can effectively increase pigmentation and provide sunburn protection, making it a promising adjunct to traditional photoprotective strategies².

Melanotan 1 and Dermatological Disorders

Melanotan-1 has shown efficacy in treating several dermatological conditions:

• Erythropoietic Protoporphyria (EPP): Approved by the European Medicines Agency for preventing phototoxicity in EPP patients, afamelanotide increases pain-free sunlight exposure³.
• Polymorphic Light Eruption (PMLE) and Solar Urticaria: Demonstrated promising results in reducing symptoms³.
• Vitiligo: Combined with narrowband UV-B phototherapy, afamelanotide promotes repigmentation by enhancing melanoblast differentiation and proliferation⁴.
• Other Conditions: Smaller studies have indicated potential benefits in treating acne, Hailey-Hailey disease, and actinic keratoses⁵.

Melanotan 1 and Neuroprotection

Melanotan-1 (under the name NDP-MSH) has been shown to ameliorate neuroinflammation and blood-brain barrier (BBB) disruption following intracerebral hemorrhage (ICH) in mice. This effect is mediated through the activation of the CREB/Nr4a1/NF-κB pathway, which results in improved neurological function and reduced expression of inflammatory markers such as p-NF-κB p65, IL-1β, and TNF-α⁶.

The peptide prevents immune cell infiltration into the central nervous system (CNS) by restoring BBB integrity, which is crucial in neuroinflammatory diseases like multiple sclerosis (MS)⁷.

NDP-MSH also reduces oxidative stress and neuronal apoptosis after ICH by activating the PI3K/Akt/Nrf2 signaling pathway. This leads to increased expression of neuroprotective proteins such as Bcl-2 and decreased levels of pro-apoptotic markers like cleaved caspase-3⁸.

In models of Parkinson’s disease, NDP-MSH modulates peripheral immune responses and reduces neuroinflammation by decreasing microglial activation and inflammatory cytokines. This neuroprotective effect is partly mediated by regulatory T cells (Tregs), which are crucial for controlling immune responses⁹.

Furthermore, NDP-MSH has shown potential in improving cognitive deficits and reducing neuroinflammation in advanced stages of Alzheimer’s disease (AD) in mouse models. It decreases levels of hyperphosphorylated Tau, although it does not affect amyloid-beta burden¹⁰.

In ischemic stroke models, NDP-MSH provides long-lasting neuroprotection and functional recovery by promoting neurogenesis and reducing neuronal loss. This effect is associated with the activation of MC4 receptors and the up-regulation of neurogenesis-related pathways such as Wnt-3A and Sonic hedgehog signaling¹¹.

References

1. Koikov, L., Starner, R., Swope, V., Upadhyay, P., Hashimoto, Y., Freeman, K., Knittel, J., Haskell-Luevano, C., & Abdel‐Malek, Z. (2021). Development of hMC1R Selective Small Agonists for Sunless Tanning and Prevention of Genotoxicity of UV in Melanocytes.. The Journal of investigative dermatology. https://doi.org/10.1016/j.jid.2020.11.034.
2. Humphrey, S., Oo, T., & Barnetson, S. (2008). Clinical potential of Melanotan® (NDP-α-MSH) in skin protection – current status and future perspective. Experimental Dermatology, 13, 578-578. https://doi.org/10.1111/J.0906-6705.2004.0212AR.X.
3. Minder, E., Barman-Aksoezen, J., & Schneider-Yin, X. (2017). Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Clinical Pharmacokinetics, 56, 815-823. https://doi.org/10.1007/s40262-016-0501-5.
4. Grimes, P., Hamzavi, I., Lebwohl, M., Ortonne, J., & Lim, H. (2013). The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo.. JAMA dermatology, 149 1, 68-73 . https://doi.org/10.1001/2013.jamadermatol.386.
5. McNeil, M., Nahhas, A., Braunberger, T., & Hamzavi, I. (2018). Afamelanotide in the Treatment of Dermatologic Disease. Skin therapy letter, 23 6, 6-10 .
6. Wu, X., Fu, S., Liu, Y., Luo, H., Li, F., Wang, Y., Gao, M., Cheng, Y., & Xie, Z. (2019). NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-κB pathway after intracerebral hemorrhage in mice. Journal of Neuroinflammation, 16. https://doi.org/10.1186/s12974-019-1591-4.
7. Mykicki, N., Herrmann, A., Schwab, N., Deenen, R., Sparwasser, T., Limmer, A., Wachsmuth, L., Klotz, L., Köhrer, K., Faber, C., Wiendl, H., Luger, T., Meuth, S., & Loser, K. (2016). Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Science Translational Medicine, 8, 362ra146 – 362ra146. https://doi.org/10.1126/scitranslmed.aaf8732.
8. Fu, S., Luo, X., Wu, X., Zhang, T., Gu, L., Wang, Y., Gao, M., Cheng, Y., & Xie, Z. (2020). Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice. Oxidative Medicine and Cellular Longevity, 2020. https://doi.org/10.1155/2020/8864100.
9. Srivastava, P., Nishiyama, S., Lin, S., Srivastava, A., Su, C., Peng, W., Levy, M., Schwarzschild, M., Xu, Y., & Chen, X. (2023). Peripheral MC1R activation modulates immune responses and is neuroprotective in a mouse model of Parkinson’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-3042571/v1.
10. Daini, E., Vandini, E., Bodria, M., Liao, W., Baraldi, C., Secco, V., Ottani, A., Zoli, M., Giuliani, D., & Vilella, A. (2023). Melanocortin receptor agonist NDP-α-MSH improves cognitive deficits and microgliosis but not amyloidosis in advanced stages of AD progression in 5XFAD and 3xTg mice. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.1082036.
11. Giuliani, D., Ottani, A., Mioni, C., Bazzani, C., Galantucci, M., Minutoli, L., Bitto, A., Zaffe, D., Botticelli, A., Squadrito, F., & Guarini, S. (2007). Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins.. European journal of pharmacology, 570 1-3, 57-65 . https://doi.org/10.1016/J.EJPHAR.2007.05.025.