What Is Melanotan 2?

Melanotan 2 (a.k.a. Melanotan II) is a synthetic (man-made) member of the melanocortin family of naturally occurring proteins. The melanocortins are hormones and signaling peptides critical to the production of melanin (pigment molecule and in the regulation of homeostatis, appetite, and sexual arousal. Melanocortins mediate their effects by binding to melanocortin receptors.

 The Effects of Melanocortins

Melanocortin (MC) receptors are found on cells throughout the body. Five different MC receptors, labeled (1) through (5), have been identified thus far. Understanding how those receptors work has allowed scientists to explore the effects of melanocortin and thus melanotan 2. Here are the effects of each MC receptor.

MC(1): MC(1) is found in melanocytes, skin cells that are responsible for the production of melanin, the pigment that imparts a dark color to the skin. It is also found on hair cells and is partially responsible, though not entirely responsible, for hair coloration.

MC(2): MC(2) is also called the adrenocorticotropic hormone receptor (ACTHR). It is found on the adrenal glands and controls the synthesis and secretion of adrenal hormones, such as the glucocorticoids. Excess stimulation of MC(2) can lead to Cushing’s syndrome. Most melanocortins do not bind to MC(2), but melanotan 2 is thought to have limited affinity.

MC(3): MC(3) plays roles in appetite control and homeostasis 1 . Unfortunately, the exact effects of MC(3) are not well understood at this point in time.

MC(4): MC(4) plays roles in feeding, sexual behavior, and male erectile function. Mutations in MC(4) have been linked to obesity2 .

MC(5): MC(5) appears to only effect exocrine glands (sweat glands and pancreatic islet cells).

The Effects

This peptide is thought to bind to MC(1), MC(2), and MC(4). Its interaction with MC(1) leads to skin darkening. Administration of melanotan 2 in test subjects has produced an average increase in tanning of about 50%. Research suggests that people could achieve the same level tanning without approximately half as much exposure to sunlight, which means less ultraviolet (UV) light exposure and thus safer tanning3 . Researchers are currently investigating whether melanotan 2 is beneficial in reducing rates of skin cancer or not.Melanotan 2

It is known to bind to MC(2), but the interaction is not thought to be substantial. Limited trials in laboratory settings have not demonstrated an increase in rates of Cushing’s disease when melanotan 2 is administered. It is still considered a hypothetical risk of the peptide.

There is a strong binding with MC(4), which makes it a potent treatment for erectile dysfunction. In fact, melanotan 2 is currently in phase I clinical trials, being investigated as a potential treatment for psychogenic erectile dysfunction4 . The erectile effects of melanotan 2 have been extensively investigated in rats 5,6 .

A final and as yet uncertain effect of melanotan II is on social anxiety. In particular, it has shown some promise in the treatment of autism. Thus far, tests have only been carried out in the prairie vole. Those tests have shown that melanotan II decreases the time required for a prairie vole to remember its lifelong companion and to resume mating7 .

Overview

Melanotan 2 is a synthetic melanocortin that binds to melanocortin receptors 1, 2, and 4. It has skin-darkening effects and is currently being investigated as a potential treatment for erectile dysfunction. It may or may not be useful as a treatment for social anxiety and autism.

Resources

 

  1. Meek, T. H. et al. Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin in male rats with uncontrolled diabetes. Endocrinology155, 4157-4167 (2014).

 

  1. Xu, Y. et al. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab.18, 860-870 (2013).

 

  1. Fitzgerald, L. M., Fryer, J. L., Dwyer, T. & Humphrey, S. M. Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles. Peptides27, 388-394 (2006).

 

  1. Wessells, H. et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urol.160, 389-393 (1998). Checkout latest news and updates at http://www.theage.com.au/victoria/melanotan2-tanning-injections-promoted-as-safe-despite-serious-concerns-20150804-giqz0l.html

 

  1. Giuliano, F., Clément, P., Droupy, S., Alexandre, L. & Bernabé, J. Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience138, 293-301 (2006).

 

  1. Kimura, Y., Naitou, Y., Wanibuchi, F. & Yamaguchi, T. 5-HT(2C) receptor activation is a common mechanism on proerectile effects of apomorphine, oxytocin and melanotan-II in rats. Eur. J. Pharmacol.589, 157-162 (2008).

 

  1. Modi, M. E. et al. Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology40, 1856-1865 (2015).