Melanotan 1 is similar to naturally occurring alpha melanocyte stimulating hormone alpha-MSH (Melanotan 2). Alpha-MSH is known for its influence on melanocytes, the cells in skin and hair responsible for pigmentation. This function is mediated via strong binding to melanocortin receptor 1. Alpha-MSH is a non-selective full agonist of melanocortin receptors 1, 3, 4, and 5. Melanotan 1 differs from alpha-MSH (Melanotan 2) by a single amino acid and was actually first developed as a sunless tanning agent. Research into melanocortin receptors and their effects, scientists quickly discovered that while melanotan 1 did indeed cause pigmentation, and altered baseline metabolism. Subsequent study of melanotan 1 and other melanocortin-binding proteins helped scientists to better understand the melanocortin signaling system.

What is Melanotan 1?

Melanotan 1 is a synthetic analogue of the naturally occurring hormone alpha-melanocyte-stimulating hormone (α-MSH). It primarily functions by binding to the melanocortin 1 receptor (MC1R), which stimulates the production of melanin, the pigment responsible for skin color. This process, known as melanogenesis, leads to increased skin pigmentation and is being explored for its potential in managing various photosensitivity disorders.

Melanotan 1 and Skin Pigmentation and Tanning

Melanotan 1, also known as Afamelanotide or MT-1, was initially developed in the late 1980s at the University of Arizona with the aim of understanding and harnessing the effects of melanocyte-stimulating hormone on skin pigmentation.

MT-1 works by stimulating melanocytes, the cells responsible for producing melanin, which leads to increased pigmentation in the skin. This property has made it a subject of interest for providing a protective tan without the need for extensive sun exposure. In clinical trials, MT-1 has been shown to enhance tanning when combined with UV-B light or sunlight exposure. Participants in these studies experienced fewer sunburn cells, suggesting a potential protective effect against UV radiation.

Melanotan 1 and Neuroprotection

Research indicates that α-MSH and its analogs can offer neuroprotection, especially in conditions like Alzheimer’s disease (AD). In studies involving transgenic mouse models of AD, stimulation of melanocortin receptors with α-MSH analogs has been shown to improve cognitive abilities. This neuroprotective effect is associated with a reduction in hyperphosphorylated Tau levels, a marker of neuronal damage, although it does not significantly affect amyloid-beta burden.

The modulation of glial reactivity and downregulation of p38 mitogen-activated protein kinase are also observed, suggesting that α-MSH may influence pathways involved in neuroinflammation.

Melanotan 1 and Anti-Inflammatory Effects

α-MSH exhibits potent anti-inflammatory properties across various tissues. It acts by binding to MC1-R, leading to the elevation of cyclic AMP, which in turn opposes the action of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α).

This peptide can inhibit the activation of nuclear factor-kappa B (NF-κB) and the upregulation of intercellular adhesion molecules, which are critical in inflammatory responses. Additionally, α-MSH has been shown to have antioxidant roles by inhibiting peroxide-stimulated activation of glutathione peroxidase.

In chondrocytes, α-MSH and its selective agonists can modulate the production of inflammatory cytokines and tissue-destructive proteins. This suggests potential therapeutic applications in conditions characterized by inflammation and tissue degradation

Melanotan 1 Peptide Structure