Melanotan is a man-made peptide analogue of alpha-melanocyte-stimulating hormone (a-MSH), a naturally occurring peptide present in the human body. a-MSH is produced by the pituitary gland that is involved in the process called melanogenesis i.e., stimulates melanocytes to produce melanin that is responsible for the pigmentation of skin.

From Pubchem

IUPAC Name:(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide
Synonyms: Melanotan II, MT-II
Molecular Formula: C50H69N15O9
Molecular Weight:1024.2 g/mol
CAS number: 121062-08-6
PubChem CID: 92432

Melanotan II was developed in the early 1990s at the University of Arizona by by Dr. Victor Hruby and Dr. Mac Hadley. The initial aim of the research was to create a compound that could stimulate melanin production in the skin as a potential treatment for skin conditions like vitiligo, where patients have patches of depigmented skin.

During the research process, one of the scientists injected himself with a high dose of Melanotan II and experienced an eight-hour of erection along with nausea and vomiting. It has gained attention and controversy due to its unregulated use as a skin tanning agent, raising concerns about its potential misuse. It has not been approved for human use sale for MT-II is restricted for research purposes only.

Melanotan II is a non-selective agonist of melanocortin receptors. There are five types of melanocortin receptors, MC1R, MC@R, MC3R, MC4R and MC5R.

• MC1 Receptor is located on the melanocytes and its stimulation by MT-II causes darkening of skin and hair.
• MC2R activation is involved in the secretion of adrenal hormones, like cortisol.
• MC3R stimulation by MT-II regulates appetite and energy homeostasis.
• MC4 receptors are mainly involved in sexual arousal and cause changes in feeding behaviour.
• MC5R can influence sebum production and temperature homeostasis.

1. Insulin Sensitivity

Studies show that Melanotan-II might be involved in improving insulin sensitivity. A study conducted on rats found that peripheral administration of MT-II can improve glucose tolerance and boost insulin sensitivity [1]. Similarly, intracerebrovascular administration of melanotan-II has been shown to enhance insulin-mediated glucose uptake. Nonetheless, it had no impact on the body's natural glucose production, suggesting that the activation of MC3R and MC4R receptors in the central nervous system affected insulin sensitivity in a tissue-specific manner, independently [2]. However, a recent clinical trial found contradictory results that 10 MT-II administration before bedtime reduced insulin sensitivity by 12% in men [3].

2. Melanoma

UV rays are well-known for their detrimental effects on skin health and their association with the development of skin cancers. They cause inflammation and induce immediate oxidative stress, leading to the production of free radicals that can damage skin cells. Additionally, scientific studies have linked UV rays to the suppression of both local and systemic immune responses. Melatonin, which possesses antioxidant properties and the ability to reduce cell death (apoptosis), offers a potential shield against the harmful effects of UV rays [4]. Furthermore, another study suggests that melanotan II, through the upregulation of PTEN and the inhibition of cyclooxygenase and prostaglandin E2, can contribute to the suppression of melanoma development [5].

3. Social Behaviour

Melanotan 2 has been known to improve poor social behaviour. A study conducted on an autism mouse model shows that MT-II administration had a positive influence on autism-like features, including reduced verbal communication, repetitive behaviors and social isolation [6]. Another study was conducted on female prairie voles, a species known for complex special behaviour, particularly in the context of monogamous pair bonding. It found that substances that stimulate oxytocin release, including melanotan 2, can promote social bonding in these species [7].

4. Sexual Health

Literature reveals that melanotan 2 is an effective therapy for men with erectile dysfunction. In research, 9 out of 10 men with psychogenic erectile dysfunction who are unable to achieve erections before sexual activity but can do so while sleeping experienced penile erections after taking MT-II [8]. The effects of this peptide are just not limited to psychogenic erectile dysfunction, it can also improve sexual dysfunction associated with several risk factors [9].

5. Appetite Regulation

Research shows that melanotan 2 regulates appetite and mediates energy expenditure. One study on male mice found that MT-II administration into the brain region involved in rewarding (nucleus accumbens) decreased the amount of food consumed and the motivation to eat [10]. Furthermore, research shows that MT-II mediates energy expenditure and appetite regulation through MC3R and MC4R activation via PMOC signaling. Alpha melanocyte-stimulating hormone signaling might be a potential target for treating obesity [11].

Melanotan II is a synthetic analog of the alpha-melanocyte-stimulating hormone, a naturally occurring peptide. It is known to stimulate melanogenesis and seems to be a promising therapy for obesity and type 2 diabetes. FDA has not approved it yet and the Melanotan 2 purchase is available for research purposes only. We encourage you to buy melanotan 2 only if you are a qualified researcher.

1. Banno, R., et al., The melanocortin agonist melanotan II increases insulin sensitivity in OLETF rats. Peptides, 2004. 25(8): p. 1279-1286.
2. Heijboer, A.C., et al., Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Diabetologia, 2005. 48(8): p. 1621-6.
3. Lauritzen, E.S., et al., Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes-A randomized placebo-controlled crossover trial. J Pineal Res, 2022. 73(1): p. E12809.
4. Goswami, S. and C. Haldar, Melatonin as a possible antidote to UV radiation-induced cutaneous damages and immune-suppression: An overview. Journal of Photochemistry and Photobiology B: Biology, 2015. 153: p. 281-288.
5. Wu, J.C., et al., Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition. Int J Mol Sci, 2020. 21(2).
6. Minakova, E., et al., Melanotan-Ii Reverses Autistic Features in a Maternal Immune Activation Mouse Model of Autism. Plos One, 2019..
7. Young, L., Drugs that stimulate oxytocin release promote social bonding in an animal model relevant to autism. Frontiers in Neuroscience, 2010. 4.
8. WESSELLS, H., et al., SYNTHETIC MELANOTROPIC PEPTIDE INITIATES ERECTIONS IN MEN WITH PSYCHOGENIC ERECTILE DYSFUNCTION: DOUBLE-BLIND, PLACEBO CONTROLLED CROSSOVER STUDY. Journal of Urology, 1998. 160(2): p. 389-393.
9. Wessells, H., et al., Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology, 2000. 56(4): p. 641-646.
10. Eliason, N.L., L. Martin, M.J. Low, and A.L. Sharpe, Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food. Neuropeptides, 2022. 96: p. 102289.
11. Hsieh, Y.-W., et al., Depletion of Alpha-Melanocyte-Stimulating Hormone Induces Insatiable Appetite and Gains in Energy Reserves and Body Weight in Zebrafish. Biomedicines, 2021. 9(8): p. 941.