Melanotan II is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

analogue of the

peptide hormone Peptide hormones are hormones composed of peptide molecules. These hormones influence the endocrine system of animals, including humans. Most hormones are classified as either amino-acid-based hormones (amines, peptides, or proteins) or steroid h ...

α-melanocyte-stimulating hormone (α-MSH) that stimulates

melanogenesis Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart foun ...

to facilitate tanning. It may also increase sexual arousal. It was developed as a successor to ''

afamelanotide Afamelanotide, sold under the brand name Scenesse, is a medication used to prevent phototoxicity and to reduce pain from light exposure for people with erythropoietic protoporphyria. It is a melanocortin 1 receptor (MC1 receptor) agonist an ...

'' ("Melanotan I"), an

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

-approved drug operating through a similar pathway. Clinuvel Pharmaceuticals intended to offer it as a cosmetic, but abandoned this pursuit in the 2000s due to regulatory restrictions and concerns about the promotion of suntanning. Unlicensed Melanotan II is found on the internet, although health agencies advise against its use due to legality and a lack of testing. Melanotan-II may cause reversible darkening of moles and freckles. It is unclear if Melanotan II can increase (or reduce) the risk of developing

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

, because reports of melanomas associated with its use have coincided with heavy UV exposure and sun bed use. A 2013 scientific review found there was no conclusive evidence it causes melanoma, and a 2021 review concluded "the increased risk of melanoma in Melanotan users, who use it for tanning and exhibit sun-seeking behaviour, can probably be explained by more UV exposure". Side effects may include facial flushing,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

erection An erection (clinically: penile erection or penile tumescence) is a Physiology, physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, ...

in males.

Synthesis

In the synthesis of melanotan II, an ε-amino group of lysine and an γ-carboxy group of aspartic acid have their orthogonal protection removed before undergoing a carbodiimide mediated lactamization, leading to an intermediate. This intermediate, when attached to N-acetylnorleucine, forms melanotan II. The entire process can be accomplished in 12 steps with an overall yield of 2.6%, and the product is more than 90% pure without preparative chromatography.

Mechanism of action

Melanotan II acts as a non-selective

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

melanocortin receptor Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins: * . MC1R is associa ...

s MC₁, MC₃, MC₄, and MC₅. Melanotan II produces

by activation of the MC₁ receptor, whereas its clinically documented sexual effects are thought to be related to its ability to activate the MC₄ receptor (though the MC₃ is thought to also possibly be involved). Other effects of melanotan II, mostly regarded as

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s, include flushing,

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

stretching Stretching is a form of physical exercise in which a specific muscle or tendon (or muscle group) is deliberately expanded and flexed in order to improve the muscle's felt elasticity and achieve comfortable muscle tone. The result is a feelin ...

yawning A yawn is a reflex in vertebrate animals characterized by a long inspiratory phase with gradual mouth gaping, followed by a brief climax (or acme) with muscle stretching, and a rapid expiratory phase with muscle relaxation, which typically last ...

, and

loss of appetite Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...

(the last via activation of MC₄).

History and research

Research in the early 1960s showed that in rats, administration of α-MSH caused sexual arousal, and work on this continued in many labs up through the 1980s, when scientists at the University of Arizona began attempting to develop α-MSH and analogs as potential

sunless tanning Sunless tanning refers to the effect of a sun tanning, suntan without exposure to the Sun. Sunless tanning involves the use of #Oral agents, oral agents (carotenids), or creams, lotions or sprays applied to the skin. Skin-applied products may be ...

agents, and synthesized and tested several analogs, including melanotan-I and melanotan II. Early in the research process one of the scientists, who was conducting experiments on himself with an early tool compound, melanotan II, injected himself with twice the dose he intended to and got an eight-hour erection, along with nausea and vomiting. As a tanning agent, melanotan I (now known as

) was licensed by Competitive Technologies, a

technology transfer Technology transfer (TT), also called transfer of technology (TOT), is the process of transferring (disseminating) technology from the person or organization that owns or holds it to another person or organization, in an attempt to transform invent ...

company operating on behalf of the University of Arizona, to an Australian startup called Epitan, which changed its name to Clinuvel in 2006. Afamelanotide was approved by the FDA in 2019. As a sexual dysfunction agent, melanotan II was licensed by Competitive Technologies to Palatin Technologies. Palatin ceased development of melanotan II in 2000 and synthesized, patented, and began to develop

bremelanotide Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, ...

, a likely metabolite of melanotan II that differs in that it has a carboxy group where melanotan II has an

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

. Clinuvel Pharmaceuticals intended to offer it as a cosmetic, but abandoned this pursuit in the 2000s. Competitive Technologies (Clinuvel) sued Palatin for breach of contract and tried to claim ownership of bremelanotide; the parties settled in 2008 with Palatin retaining rights to bremelanotide, returning rights to melanotan II to Competitive Technologies, and paying US$800,000. Melanotan-II may cause reversible darkening of moles and freckles. It is unclear if Melanotan II can increase (or reduce) the risk of developing

. Reports of melanomas associated with the use of Melanotan II have coincided with heavy sunbathing and sun bed use. A 2013 scientific review found there was no conclusive evidence it causes melanoma, and a 2021 review concluded "the increased risk of melanoma in Melanotan users, who use it for tanning and exhibit sun-seeking behaviour, can probably be explained by more UV exposure". A 2020 in vivo study found that Melanotan II suppressed the progression of melanomas.

Society and culture

Numerous products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" or "melanotan-2" in their marketing. The unregulated products are not legal to be sold for human usage in any jurisdiction. Starting in 2007, health agencies in various countries began issuing warnings against their use.

References

{{Melanocortin receptor modulators Melanocortin receptor agonists Peptides Abandoned drugs Aphrodisiacs

Synthesis

Mechanism of action

History and research

Society and culture

See also

References