It was developed as a successor toafamelanotide ("Melanotan I"), anFDA-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 lack of testing and regulatory approval.
Melanotan-II may cause reversible darkening of moles and freckles. It is unclear if Melanotan II can increase (or reduce) the risk of developingmelanoma, because reports of melanomas associated with its use have coincided with heavy UV exposure and sun bed use.[1][2] A 2013 scientific review found there was no conclusive evidence it causes melanoma,[1] 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".[2]
Side effects may include facial flushing,nausea anderection in males.
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.[3]
Melanotan II producesmelanogenesis 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).[5][6]
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 potentialsunless tanning agents, and synthesized and tested several analogs, includingmelanotan-I and melanotan II.[6][9]
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.[6][non-primary source needed]
As a tanning agent, melanotan I (now known asafamelanotide) was licensed by Competitive Technologies, atechnology transfer company operating on behalf of the University of Arizona, to an Australian startup called Epitan,[10][11] which changed its name to Clinuvel in 2006.[12] Afamelanotide was approved by the FDA in 2019.[2]
As a sexual dysfunction agent, melanotan II was licensed by Competitive Technologies to Palatin Technologies.[9] Palatin ceased development of melanotan II in 2000 and synthesized, patented, and began to developbremelanotide, a likely metabolite of melanotan II that differs in that it has acarboxy group where melanotan II has anamide.[6][13]
Clinuvel Pharmaceuticals intended to offer it as a cosmetic, but abandoned this pursuit in the 2000s.[14]
Competitive Technologies (Clinuvel) sued Palatin for breach of contract and tried to claim ownership of bremelanotide;[13] the parties settled in 2008 with Palatin retaining rights to bremelanotide, returning rights to melanotan II to Competitive Technologies, and paying US$800,000.[15]
Melanotan-II may cause reversible darkening of moles and freckles. It is unclear if Melanotan II can increase (or reduce) the risk of developingmelanoma. Reports of melanomas associated with the use of Melanotan II have coincided with heavy sunbathing and sun bed use.[1][2] A 2013 scientific review found there was no conclusive evidence it causes melanoma,[1] 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".[2] A 2020 in vivo study found that Melanotan II suppressed the progression of melanomas.[16]
Numerous products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1", "melanotan-2" or "Barbie drug" in their marketing.[17][18][19][20] Sale of these products for human use is illegal in many jurisdictions.[21][22][23][24]
Starting in 2007, health agencies in various countries began issuing warnings against their use.[25][26][27][28][29][30]
^Langan EA, Ramlogan D, Jamieson LA, Rhodes LE (January 2009). "Change in moles linked to use of unlicensed "sun tan jab"".BMJ.338: b277.doi:10.1136/bmj.b277.PMID19174439.S2CID27838904.
