Melanotan II

Melanotan II
Names
Pronunciation /mɛˈlænoʊtæn/ ( listen)
Other names

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2


Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
Ac-cyclo[Nle4, Asp5,D-Phe7, Lys10]α-MSH4–10-NH2
N-Acetyl-L-norleucyl-L-α-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysinamide (2→7)-lactam
PT-14

MT II
Identifiers
ChEMBL
ChemSpider
MeSH melanotan-II
Properties
C50H69N15O9
Molar mass 1024.180
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is ☑Y☒N ?)
Infobox references
Structure of melanotan II (full size)

Melanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH).

It was under development as drug candidate for female sexual dysfunction and erectile dysfunction but clinical development ceased by 2003, and as of 2018, no product containing melanotan II was marketed and all commercial development had ceased.[1] Unlicensed, untested, or fraudulent products sold as "melanotan II" are found on the Internet, and purported to be effective as "tanning drugs", though side effects such as uneven pigmentation, new nevi (moles), and darkening or enlargement of existing moles are common and have led to medical authorities discouraging use.[2][3]

Mechanism of action

Melanotan II acts as a non-selective agonist of the melanocortin receptors, MC1, MC3, MC4, MC5.[4]

To the extent that melanotan II produces melanogenesis, this is thought to be caused 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 possibly also be involved).[5][6]

Other effects of melanotan II, mostly regarded as adverse effects, include flushing, nausea, vomiting, stretching, yawning, and loss of appetite (the last via activation of MC4).[7][8]

History

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 University of Arizona began attempting to develop α-MSH and analogs as potential sunless tanning agents, and synthesized and tested several analogs, including melanotan-I and melanotan II.[6][9]

Very early in the 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 and got an eight-hour erection, along with nausea and vomiting.[6]

To pursue the tanning agent, melanotan-I (now known as afamelanotide) was licensed by Competitive Technologies, a technology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan,[10][11] which changed its name to Clinuvel in 2006.[12]

To pursue the 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 develop bremelanotide, a likely metabolite of melanotan-II that differs from melanotan-II in that it has a hydroxyl group where melanotan-II has an amide.[6][13] Competitive Technologies sued Palatin for breach of contract and to try 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 $800,000.[14]

Society and culture

A number of products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" or "melanotan-2" in their marketing.[15][16][17]

The unregulated products are not legal to be sold for human usage in any jurisdiction.[18][19][20][21]

Starting in 2007 health agencies in various counties began issuing warnings against their use.[22][23][24][25][26][27]

See also

References

  1. ↑ "Melanotan II". AdisInsight. Retrieved 13 Jan 2018.
  2. ↑ Brennan R, Wells JS, Van Hout MC (September 2017). "The injecting use of image and performance-enhancing drugs (IPED) in the general population: a systematic review". Health & Social Care in the Community. 25 (5): 1459–1531. doi:10.1111/hsc.12326. PMID 26806443.
  3. ↑ Habbema L, Halk AB, Neumann M, Bergman W (October 2017). "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review". International Journal of Dermatology. 56 (10): 975–980. doi:10.1111/ijd.13585. PMID 28266027.
  4. ↑ Wikberg JE (2001). "Melanocortin receptors: new opportunities in drug discovery". Expert Opinion on Therapeutic Patents. 11 (1): 61–76. doi:10.1517/13543776.11.1.61. ISSN 1354-3776.
  5. ↑ Norris DO, Lopez KH (25 November 2010). Hormones and Reproduction of Vertebrates. Academic Press. pp. 4–. ISBN 978-0-08-095809-5.
  6. 1 2 3 4 King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H (2007). "Melanocortin receptors, melanotropic peptides and penile erection". Curr Top Med Chem. 7 (11): 1098–1106. doi:10.2174/1568026610707011111. PMC 2694735. PMID 17584130.
  7. ↑ Plant TM, Zeleznik AJ (15 November 2014). Knobil and Neill's Physiology of Reproduction: Two-Volume Set. Academic Press. pp. 2230–. ISBN 978-0-12-397769-4.
  8. ↑ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (28 September 2011). Campbell-Walsh Urology. Elsevier Health Sciences. pp. 743–. ISBN 978-1-4557-2298-3.
  9. 1 2 Hadley ME (October 2005). "Discovery that a melanocortin regulates sexual functions in male and female humans". Peptides. 26 (10): 1687–9. doi:10.1016/j.peptides.2005.01.023. PMID 15996790.
  10. ↑ "EpiTan focuses on Melanotan, a potential blockbuster". The Pharma Letter. 1 November 2004.
  11. ↑ Hadley ME, Dorr RT (April 2006). "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization". Peptides. 27 (4): 921–30. doi:10.1016/j.peptides.2005.01.029. PMID 16412534.
  12. ↑ "Epitan changes name to Clinuvel, announces new clinical program". LabOnline. 27 February 2006.
  13. 1 2 "Press Release: Palatin Technologies Refutes Competitive Technologies Contention of Material Breach". Palatin Technologies via PR Newswire. September 12, 2007.
  14. ↑ "Press Release: Palatin Technologies Announces Litigation Settlement With Competitive Technologies". Palatin Technologies via PR Newswire. January 22, 2008.
  15. ↑ "Believe It Or Not 'Tanorexia' A Very Real Problem". WCBS-TV, CBS. 2009-05-20. Archived from the original on May 21, 2009. Retrieved 2009-07-23.
  16. ↑ "Fools Gold". Cosmopolitan (Australia). 2009-06-14. Archived from the original on 2009-09-12. Retrieved 2009-07-25.
  17. ↑ Madrigal A (2009-01-29). "Suntan Drug Greenlighted for Trials". Wired. Archived from the original on 5 May 2009. Retrieved 2009-04-11.
  18. ↑ "Tanning drug a health risk". Herald Sun. 2009-10-31. Retrieved 2009-10-31.
  19. ↑ Langan EA, Nie Z, Rhodes LE (September 2010). "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?". The British Journal of Dermatology. 163 (3): 451–5. doi:10.1111/j.1365-2133.2010.09891.x. PMID 20545686.
  20. ↑ 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. PMID 19174439.
  21. ↑ "Risky tan jab warnings 'ignored'". BBC. 2009-02-18. Archived from the original on 21 February 2009. Retrieved 2009-03-04.
  22. ↑ "Warning against the product Melanotan". Danish Medicines Agency. 2008. Retrieved 2008-08-11.
  23. ↑ ""Tan jab" is an unlicensed medicine and may not be safe". MHRA. 2008. Archived from the original on 2008-12-18. Retrieved 2008-11-17.
  24. ↑ "US Lab Research Inc Warning letter". U.S. Food and Drug Administration. 2009-01-29. Archived from the original on 10 July 2009. Retrieved 2009-07-23.
  25. ↑ "Melanotan Powder for Injection". Notice Information: – Warning – 27 February 2009. Irish Medicines Board. 2009. Retrieved 2009-02-02.
  26. ↑ "Legemiddelverket advarer mot bruk av Melanotan". Norwegian Medicines Agency. 2007-12-13. Archived from the original on 17 April 2009. Retrieved 2009-03-11.
  27. ↑ "Melanotan – farlig og ulovlig brunfarge". Norwegian Medicines Agency. 2009-01-23. Archived from the original on 17 April 2009. Retrieved 2009-03-11.
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