Echidna and Melanotan: Difference between pages
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{{nofootnotes|date=May 2008}} |
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| ImageFile = melanotan.png |
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{{dablink|For other senses of this word, see [[Echidna (disambiguation)]].}} |
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{{Taxobox |
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| IUPACName = |
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| name = Echidnas<ref name=MSW3>{{MSW3 Groves|pages=p. 1-2|id=10300002}}</ref> |
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| Name = Melanotan 1 |
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| image = Long-beakedEchidna.jpg |
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| OtherNames = Melanotan, afamelanotide, CUV1647 |
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| image_caption = [[Western Long-beaked Echidna]] |
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| Section1 = {{Chembox Identifiers |
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| fossil_range = {{Fossil range|Miocene|Recent}} |
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| CASNo = 75921-69-6 |
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| PubChem = |
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| phylum = [[Chordate|Chordata]] |
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| SMILES = |
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| classis = [[Mammal]]ia |
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| MeSHName = Melanotan-1 |
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| ordo = [[Monotremata]] |
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}} |
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| familia = '''Tachyglossidae''' |
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| Section2 = {{Chembox Properties |
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| familia_authority = [[Theodore Nicholas Gill|Gill]], 1872 |
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| Formula = |
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| subdivision_ranks = [[Species]] |
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| MolarMass = |
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| Appearance = |
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Genus ''[[Tachyglossus]]'' <br/> |
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| Density = |
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''[[Short-beaked Echidna|T. aculeatus]]''<br/> |
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| MeltingPt = |
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Genus ''[[Zaglossus]]'' <br/> |
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''[[Sir David's Long-beaked Echidna|Z. attenboroughi]]''<br/> |
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}} |
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''[[Western Long-beaked Echidna|Z. bruijnii]]''<br/> |
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| Section3 = {{Chembox Hazards |
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''[[Eastern Long-beaked Echidna|Z. bartoni]]''<br/> |
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| Solubility = |
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†''[[Zaglossus hacketti|Z. hacketti]]''<br/> |
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| MainHazards = |
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†''[[Zaglossus robustus|Z. robustus]]''<br/> |
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| FlashPt = |
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Genus †''[[Megalibgwilia]]''<br/> |
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| Autoignition = |
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†''[[Megalibgwilia|M. ramsayi]]''<br/> |
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}} |
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†''[[Megalibgwilia|M. robusta]]''<br/> |
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}} |
}} |
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[[Image:Echidna, Exmouth.jpg|thumb|A [[Short-beaked Echidna]] curled into a ball; the snout is visible on the right.]] |
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| ImageFile = Melanotan_II_chemical_structure.png |
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[[Image:EchidnainCanberra.JPG|right|thumb|In Australia the [[Short-beaked Echidna]] may be found in many environments, including urban parkland such as the shores of [[Lake Burley Griffin]] in [[Canberra]], as depicted here.]] |
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[[Image:French Island Echidna.ogg|right|thumb|A [[French Island National Park|French Island]] echidna building a defensive burrow (0:43s)]] |
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| IUPACName = |
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'''Echidnas''' ({{pronEng|ɨˈkɪdnə}}), also known as '''spiny anteaters''',<ref>http://www.enchantedlearning.com/subjects/mammals/echidna/Echidnaprintout.shtml Retrieved on [[21 October]] [[2007]]</ref> are four [[Extant taxon|extant]] [[mammal]] species belonging to the '''Tachyglossidae''' [[Family (biology)|family]] of the [[monotreme]]s. Together with the [[Platypus]], they are the only surviving members of that [[order (biology)|order]]. Although their diet consists largely of ants and termites, they are not actually related to the [[anteater]] species. They live in [[New Guinea]] and [[Australia]]. The echidnas are named after a [[Echidna (mythology)|monster in ancient Greek mythology]]. |
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| Name = Melanotan II |
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| OtherNames = |
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| Section1 = {{Chembox Identifiers |
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| CASNo = 121062-08-6 |
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| PubChem = 92432 |
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| SMILES = |
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| MeSHName = melanotan-II |
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}} |
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| Section2 = {{Chembox Properties |
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| Formula = C<sub>50</sub>H<sub>69</sub>N<sub>15</sub>O<sub>9</sub> |
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| MolarMass = 1024.180 |
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| Appearance = |
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| Density = |
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| MeltingPt = |
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| BoilingPt = |
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}} |
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| Section3 = {{Chembox Hazards |
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| Solubility = |
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| MainHazards = |
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| FlashPt = |
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| Autoignition = |
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}} |
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}} |
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:''Note: this article describes both melanotan and melanotan II: although their names are similar, they have different chemical and biological properties.'' |
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'''Melanotan 1''' and '''melanotan II''' are both [[Analog (chemistry)|analogs]] of the [[peptide]] [[hormone]] [[melanocyte stimulating hormone|alpha-melanocyte stimulating hormone]] (α-MSH) that have been shown to induce skin [[sun tanning|tanning]] in preliminary studies and clinical trials. Melanotan II has the additional effect of increasing [[libido]]. |
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Derivatives of both peptides are in development by [[pharmaceutical companies]], but as of 2008 no melanotan I or II based compound has been [[Regulation of therapeutic goods|approved for use]] by drug regulatory bodies. Unlicensed and untested melanotan products are sold through the Internet <ref name="MSN">{{Cite web|url=http://style.uk.msn.com/fashionandbeauty/bebeautiful/article.aspx?cp-documentid=5568393|title=The Dark Side of Beauty Pills|accessdate=2008-08-21|publisher=MSN.com|year=2008|format=[[HTML]]}}</ref>{{Specify|date=August 2008}} however, regulatory bodies have warned consumers they may be unsafe and ineffective. |
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== Historical development == |
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Both peptides were identified at the [[University of Arizona]]. Researchers there knew that one of the best defenses against [[skin cancer]] was a natural tan which has been slowly developed over weeks. They hypothesized that an effective way to reduce skin cancer rates in people would be to induce the body's natural tanning system to produce a protective tan prior to UV exposure. The body's naturally occurring hormone alpha-melanocyte stimulating hormone (α-MSH) causes [[melanogenesis]], a process by which the skin's tanning cells ([[melanocyte]]s) produce the skin's tanning pigment ([[melanin]]). With that knowledge they tested to see if administering this hormone to the body directly could be an effective method to cause [[sunless tanning]]. What they found was that while it appeared to work, natural alpha-MSH had too short a [[half life]] in the body to be practical as a therapeutic drug. So they decided to find a more potent and stable alternative, one that would be more practical. |
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After synthesizing and screening hundreds of molecules, the researchers headed by Dr. Victor Hruby, found a [[peptide]] that after trials and testing seemed to be approximately 1,000 times more potent than natural α-MSH. <ref name="Arizona_Daily_Star">{{Cite web|url=http://www.azstarnet.com/altsn/snredesign/relatedarticles/121038|title=UA-developed synthetic hormones speed a tan|accessdate=2007-09-22|publisher=[[Arizona Daily Star]]|year=2006|format=HTML}}</ref> They dubbed this new peptide Melanotan. Since their discovery, numerous studies dating back to the mid-1980s have shown no obvious toxic effects of the Melanotan peptides (then known by their scientific names [Nle<sup>4</sup>, <small>D</small>-Phe<sup>7</sup>]-α-MSH and Ac-Nle-''cyclo''[Asp-His-<small>D</small>-Phe-Arg-Trp-Lys]-NH<sub>2</sub>). The scientists hoped to use Melanotan as a drug to combat [[melanoma]] by stimulating the body's natural tanning mechanism to create a tan without first needing exposure to harmful levels of [[UV]] radiation. <ref name="TV3-New-Zealand">{{Cite web|url=http://www.3news.co.nz/Lifestyle/Story/tabid/420/articleID/34581/cat/84/Default.aspx|title=The Barbie Drug|accessdate=2007-09-16|publisher=[[Campbell Live]], [[TV3 (New Zealand)|TV3]]|year=2007|format=[[HTML]],[[WMV]]}}</ref> This in turn, they hypothesized, could reduce the potential for skin damage that can eventually lead to skin cancer. |
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The scientists licensed their patented peptides, via a [[technology transfer]] company, to a number of biotechnology companies who intend to develop them into drugs.<ref name="Tech transfer">{{Cite web|url=http://findarticles.com/p/articles/mi_m0EIN/is_2005_July_26/ai_n14820840|title=Competitive Technologies Licenses Additional Patent to Melanotan Corporation, Receives Additional Shares of Epitan|accessdate=2008-08-22|publisher=Business Wire|year=2005|format=[[HTML]]}}</ref> |
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==Description== |
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[[Image:Wild shortbeak echidna.jpg|thumb|left|Short-beaked Echidna]] |
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Echidnas are small mammals that are covered with coarse [[hair]] and [[spine (biology)|spines]]. They are endangered. Superficially they resemble the anteaters of South America, and other spiny mammals like [[hedgehog]]s and [[porcupine]]s. They have snouts which have the functions of both the mouth and nose. Their snouts are elongated and slender. They have very short, strong [[Limb (anatomy)|limb]]s with large [[claw]]s and are powerful diggers. Echidnas have a tiny [[mouth]] and a toothless [[jaw]]. They feed by tearing open soft logs, [[anthill]]s and the like, and use their long, sticky [[tongue]] which protrudes from their snout to collect their prey. The [[Short-beaked Echidna]]'s diet consists largely of ants and termites, while the ''Zaglossus'' species typically eat worms and insect larvae. |
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== Peptide properties and clinical trial information== |
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The long-beaked echidnas have tiny spines on their tongues that help capture their meals. |
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=== Melanotan 1 === |
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'''Melanotan 1''' has the [[Peptide sequence|amino acid sequence]] Ac-Ser-Tyr-Ser-Nle-Glu-His-<small>D</small>-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH<sub>2</sub> or [Nle<sup>4</sup>, <small>D</small>-Phe<sup>7</sup>]-alpha-MSH. |
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Melanotan is currently being tested, developed, and clinically trialed under the [[International Nonproprietary Name]] ''afamelanotide'' (formerly the [[proprietary]] CUV1647)<ref name="Clinuvel-INN">{{Cite web|url=http://www.clinuvel.com/resources/pdf/asx_announcements/2008/20080617WHOGenericName.pdf|title=World Health Organisation assigns CUV1647 generic name|accessdate=2008-06-17|publisher=Clinuvel|year=2008|format=[[Portable Document Format|PDF]]}}</ref> by the [[Australia]]n company [[Clinuvel Pharmaceuticals]], for a series of skin related diseases including [[polymorphous light eruption]] (PMLE) and [[actinic keratosis]] (AK). |
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Echidnas and the Platypus are the only egg-laying mammals, known as monotremes. The female lays a single soft-shelled, leathery [[egg (biology)|egg]] twenty-two days after mating and deposits it directly into her pouch. Hatching takes ten days; the young echidna, called a [[puggle]], then sucks [[milk]] from the [[lactiferous duct|pore]]s of the two [[Mammary gland|milk patches]] (monotremes have no [[nipple]]s) and remains in the pouch for forty-five to fifty-five days, at which time it starts to develop spines. The mother digs a nursery burrow and deposits the puggle, returning every five days to suckle it until it is weaned at seven months. |
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A 1991 clinical [[Investigational new drug]] trial conducted at the Department of Internal Medicine, University of Arizona Health Sciences Center was carried out with Melanotan (then known by its chemical constituents [Nle<sup>4</sup>, <small>D</small>-Phe<sup>7</sup>] (NDP)-alpha-melanocyte-stimulating hormone) with 28, "healthy white men" who used a, "high-potency sunscreen during the trial" and concluded, "Human skin darkens as a response to a synthetic [[Melanocyte-stimulating hormone|melanotropin]] given by subcutaneous injection. Skin tanning appears possible without potentially harmful exposure to ultraviolet radiation." <ref name="1991-UofA-IND-trial">{{Cite web|url=http://jama.ama-assn.org/cgi/content/abstract/266/19/2730|title=Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin|accessdate=2008-10-13|publisher=[[Journal of the American Medical Association]]|year=1991|work=Vol. 266 No. 19, November 20, 1991|format=[[HTML]]}}</ref> |
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Male echidnas have a four-headed [[penis]], but only two of the heads are used during mating. The other two heads "shut down" and do not grow in size. The heads used are swapped each time the mammal copulates.<ref>{{cite web | author = Shultz, N. | date = [[2007-10-26]] | url = http://environment.newscientist.com/article.ns?id=dn12838 | title = Exhibitionist spiny anteater reveals bizarre penis | work = [[New Scientist]] [http://www.newscientist.com/home.ns website] | accessdate = 2006-10-27}}</ref> |
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A clinical trial by the Department of Pharmacology and Arizona Cancer Center to determine increases of [[eumelanin]] expression in seven, "normal volunteers" for Melanotan published in 2000 concluded that, "results show that the tanning induced by Melanotan in the face and forearm is associated with a significant increase in the eumelanin content of the human skin." <ref name="2000-UofA-eumelanin-trial">{{Cite web|url=http://www.ncbi.nlm.nih.gov/pubmed/11045725?dopt=AbstractPlus|title=Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle<sup>4</sup>-<small>D</small>-Phe<sup>7</sup>]-alpha-MSH in humans|accessdate=2008-10-13|publisher=Photochemistry and Photobiology|year=2000|work=Volume 72 Issue 4, Pages 526 - 532|format=[[HTML]]}}</ref> |
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==Taxonomy== |
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Echidnas are [[biological classification|classified]] into three [[genus|genera]]. The ''[[Zaglossus]]'' genus includes three extant [[species]] and two species known only from [[fossil]]s, while only one species from the genus ''[[Tachyglossus]]'' is known. The third genus, ''[[Megalibgwilia]]'', is only known from fossils. |
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A [[Clinical trial#Phase_II|Phase II clinical human trial]] study conducted in 2003 at the [[University of Sydney]] demonstrated in a group of eighty volunteers that Melanotan caused a highly significant increase in skin-melanin. It found fairer-skin people ([[Fitzpatrick scale|Fitzpatrick Types I/II]], those who never tan and only burn and those who can tan in a limited fashion) recorded increases in melanin of up to 100% in some areas and that sunburn injury was reduced by more than 50% in fair skinned volunteers. <ref name="Barnetson-2003-clinical-study-bbc">{{Cite web|url=http://news.bbc.co.uk/2/hi/health/3287475.stm|title=Suntan could come 'in an implant'|accessdate=2008-10-12|publisher=[[BBC News]]|year=2003|format=[[HTML]]}}</ref><ref name="Barnetson-2003-clinical-study">{{Cite web|url=http://www.innovations-report.com/html/reports/medicine_health/report-23770.html|title=Sunburn Trial Results Show Drug Can Reduce Sun Damage by 50% for Fair-Skinned People, says Trial Head|accessdate=2008-08-22|publisher=innovations report|year=2003|format=[[HTML]]}}</ref> |
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===''Zaglossus''=== |
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The three living ''Zaglossus'' species are [[endemic (ecology)|endemic]] to [[New Guinea]]. They are rare and are hunted for food. They forage in leaf litter on the forest floor, eating [[earthworm]]s and [[insect]]s. The species are: |
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=== Melanotan II === |
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*the [[Western Long-beaked Echidna]] (''Zaglossus bruijni'') of the highland [[forest]]s |
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'''Melanotan II''' has tanning and [[aphrodisiac]] properties. <ref name="CNN-article">{{Cite web|url=http://www.cnn.com/HEALTH/men/9906/17/viagra.alternative/|title=CNN.com "Tanning drug may find new life as Viagra alternative"|accessdate=2008-06-12|publisher=[[CNN]]|year=1999|format=HTML}}</ref><ref name="Time">{{Cite web|url=http://www.time.com/time/magazine/article/0,9171,1101990628-27167,00.html|title=Tanning Bonus|accessdate=2008-09-17|publisher=[[Time (magazine)|Time]]|year=1999|format=HTML}}</ref> |
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*[[Sir David's Long-beaked Echidna]] (''Zaglossus attenboroughi''), recently discovered, prefers a still higher habitat |
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*the [[Eastern Long-beaked Echidna]] (''Zaglossus bartoni''), of which four distinct subspecies have been identified |
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It is a cyclic [[lactam]] analog of alpha-MSH with the amino acid sequence Ac-Nle-''cyclo''[Asp-His-<small>D</small>-Phe-Arg-Trp-Lys]-NH<sub>2</sub>. |
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The two fossil species are: |
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A pilot [[Clinical trial#Phase_I|Phase I clinical trial]] conducted on three males by the [[Medical school|College of Medicine]], [[Pharmacology]] Department, [[University of Arizona]] in [[Tucson, Arizona]] published in 1996 demonstrated that, "Melanotan II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection." The side effects reported were mild nausea and a "stretching and yawning complex" that correlated with spontaneous [[Erection|penile erection]]s. <ref name="Life-Sciences">{{Cite web|url=http://www.ncbi.nlm.nih.gov/pubmed/8637402|title=Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.|publisher=Elsevier Science Inc.|year=1996|work=Life Sciences, Volume 58, Issue 20, 12 April 1996, Pages 1777-1784|format=HTML}}</ref> |
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*''[[Long-beaked echidna#Zaglossus robustus|Zaglossus robustus]]'' |
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*''[[Long-beaked echidna#Zaglossus hacketti|Zaglossus hacketti]]'' |
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A clinical study published in 2000 of 20 men with psychogenic and organic erectile dysfunction conducted at the Section of Urology of The University of Arizona College of Medicine concluded, "that Melanotan II is a potent initiator of penile erection in men with erectile dysfunction." <ref name="Journal-of-Impotence-Research">{{Cite web|url=http://www.ncbi.nlm.nih.gov/pubmed/11035391?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|title=Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.|publisher=International Journal of Impotence Research|year=2000|work=12, Suppl 4, S74-S79|format=HTML}}</ref> |
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===''Tachyglossus''=== |
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==== Bremelanotide ==== |
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The [[Short-beaked Echidna]] (''Tachyglossus aculeatus'') is found in southeast [[New Guinea]] and also occurs in almost all [[Australia]]n environments, from the snow-clad [[Australian Alps]] to the deep [[desert]]s of the [[Outback]], essentially anywhere that ants and termites are available. Its size is smaller than the ''Zaglossus'' species, and it has longer hair. |
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{{main|Bremelanotide}} |
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[[Palatin Technologies]] developed another hormone originally targeted towards [[sexual dysfunction]] based upon melanotan II called bremelanotide (formerly PT-141). Bremelanotide is a [[metabolite]] of melanotan II that lacks the [[C-terminus|C-terminal]] [[amide]] [[functional group|function]]. In 2008, development for sexual dysfunction was discontinued after concerns were raised by the [[U.S. Food and Drug Administration]] (FDA) about the adverse side effect of increased blood pressure found in Phase II clinical trials. Concurrently the company announced plans to develop it as a treatment for [[Shock (medical)#Hypovolemic shock|hemorrhagic shock]] instead. <ref name="Discontinued">{{Cite web|url=http://palatin.com/news/news.asp?param=202|title=Palatin Technologies announces new strategic objectives and reports third quarter 2008 financial results|accessdate=2008-08-21|publisher=Palatin Technologies|year=2008|format=HTML}}</ref> |
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== Drug agency warnings == |
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===''Megalibgwilia''=== |
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In 2007, the FDA issued a warning to an American vendor illegally marketing melanotan II on the internet as a drug that prevents skin cancer and assists tanning. The FDA has not licensed melanotan II, and explained: "There is no evidence that the product is [[generally recognized as safe and effective]] [GRAS/E] for its labeled uses." <ref name="FDA warning">{{Cite web|url=http://www.fda.gov/consumer/updates/melanotan090507.html|title=FDA Warns About Unapproved Product, Melanotan II|accessdate=2008-08-21|publisher=[[U.S. Food and Drug Administration]]|year=2007|format=HTML}}</ref> |
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The genus ''[[Megalibgwilia]]'' is only known from fossils: |
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On August 8, 2008 the [[Danish Medicines Agency]] (DMA) issued a warning<ref name="Danish Medicines Board">{{Cite web|url=http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=13865|title=Warning against the product Melanotan|accessdate=2008-08-11|publisher=[[Danish Medicines Agency]]|year=2008|format=HTML}}</ref> against the usage of Melanotan purchased on the internet, noting that claims that imply that it has an, "effect" for protection against [[skin cancer]], "has not been documented". The DMA further warned that Melanotan has not undergone tests for its effect and possible side effects, and that it is not licensed for usage in the EU or the USA. |
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*''Megalibgwilia ramsayi'' from [[Late Pleistocene]] sites in Australia |
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*''Megalibgwilia robusta'' from [[Miocene]] sites in Australia |
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==References== |
==References== |
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{{reflist}} |
{{reflist}} |
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* Flannery, T.F. and Groves, C.P. (1998) A revision of the genus ''Zaglossus'' (Monotremata, Tachyglossidae), with description of new species and subspecies. ''Mammalia'' '''62''', 367-396. |
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* Parker, J., "[http://www.abc.net.au/science/scribblygum/June2000/default.htm Echidna Love Trains]", "Scribbly Gum" online magazine. |
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* Rismiller, P., "[http://www.earthwatch.org/site/pp2.asp?c=dsJSK6PFJnH&b=1147621 Echidnas and Goannas of Kangaroo Island]", [[Earthwatch|Earthwatch Institute]]. |
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==External links== |
== External links == |
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* [http://www.clinuvel.com/ Clinuvel Pharmaceuticals Limited]<!-- • [http://www.clinuvel.com/IRM/content/images/EpiTan_high.wmv Clinuvel (formerly Epitan) Melanotan explanational video] [http://www.clinuvel.com/IRM/content/images/EpiTan_low.wmv low bandwidth version] ([[Windows Media Video|wmv]]) --> |
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{{commons|Tachyglossidae|Echidna}} |
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* [http://melanotan.org/ Melanotan.org] |
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{{Wikispecies|Tachyglossidae}} |
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* [http://www.wired.com/wired/archive/10.06/melanotan_pr.html Wired 10.06: Thin! Tan! Hotter Than Hell!] |
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* [http://www.nwf.org/nationalwildlife/article.cfm?articleId=763&issueId=61 "The Enigma of the Echidna"] by Doug Stewart, ''National Wildlife,'' April/May 2003. |
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* [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=734258 PubChem entry] Melanotan 1 |
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* [http://www.abc.net.au/science/scribblygum/June2000/default.htm Scribbly Gum - Australian Broadcasting Corporation online magazine], article "Echidna Love Trains": Echidna spotting, Trains (breeding behaviour), The amazing puggle (young), Species, Dreaming (REM sleep), Managing populations; June 2000 |
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* [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=669326 PubChem entry Melanotan II] |
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* [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=10486716 PubChem entry ''rac''-Melanotan II] (racemic Phe) |
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Revision as of 00:37, 14 October 2008
Template:Chembox new Template:Chembox new
- Note: this article describes both melanotan and melanotan II: although their names are similar, they have different chemical and biological properties.
Melanotan 1 and melanotan II are both analogs of the peptide hormone alpha-melanocyte stimulating hormone (α-MSH) that have been shown to induce skin tanning in preliminary studies and clinical trials. Melanotan II has the additional effect of increasing libido. Derivatives of both peptides are in development by pharmaceutical companies, but as of 2008 no melanotan I or II based compound has been approved for use by drug regulatory bodies. Unlicensed and untested melanotan products are sold through the Internet [1][specify] however, regulatory bodies have warned consumers they may be unsafe and ineffective.
Historical development
Both peptides were identified at the University of Arizona. Researchers there knew that one of the best defenses against skin cancer was a natural tan which has been slowly developed over weeks. They hypothesized that an effective way to reduce skin cancer rates in people would be to induce the body's natural tanning system to produce a protective tan prior to UV exposure. The body's naturally occurring hormone alpha-melanocyte stimulating hormone (α-MSH) causes melanogenesis, a process by which the skin's tanning cells (melanocytes) produce the skin's tanning pigment (melanin). With that knowledge they tested to see if administering this hormone to the body directly could be an effective method to cause sunless tanning. What they found was that while it appeared to work, natural alpha-MSH had too short a half life in the body to be practical as a therapeutic drug. So they decided to find a more potent and stable alternative, one that would be more practical.
After synthesizing and screening hundreds of molecules, the researchers headed by Dr. Victor Hruby, found a peptide that after trials and testing seemed to be approximately 1,000 times more potent than natural α-MSH. [2] They dubbed this new peptide Melanotan. Since their discovery, numerous studies dating back to the mid-1980s have shown no obvious toxic effects of the Melanotan peptides (then known by their scientific names [Nle4, D-Phe7]-α-MSH and Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2). The scientists hoped to use Melanotan as a drug to combat melanoma by stimulating the body's natural tanning mechanism to create a tan without first needing exposure to harmful levels of UV radiation. [3] This in turn, they hypothesized, could reduce the potential for skin damage that can eventually lead to skin cancer.
The scientists licensed their patented peptides, via a technology transfer company, to a number of biotechnology companies who intend to develop them into drugs.[4]
Peptide properties and clinical trial information
Melanotan 1
Melanotan 1 has the amino acid sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 or [Nle4, D-Phe7]-alpha-MSH.
Melanotan is currently being tested, developed, and clinically trialed under the International Nonproprietary Name afamelanotide (formerly the proprietary CUV1647)[5] by the Australian company Clinuvel Pharmaceuticals, for a series of skin related diseases including polymorphous light eruption (PMLE) and actinic keratosis (AK).
A 1991 clinical Investigational new drug trial conducted at the Department of Internal Medicine, University of Arizona Health Sciences Center was carried out with Melanotan (then known by its chemical constituents [Nle4, D-Phe7] (NDP)-alpha-melanocyte-stimulating hormone) with 28, "healthy white men" who used a, "high-potency sunscreen during the trial" and concluded, "Human skin darkens as a response to a synthetic melanotropin given by subcutaneous injection. Skin tanning appears possible without potentially harmful exposure to ultraviolet radiation." [6]
A clinical trial by the Department of Pharmacology and Arizona Cancer Center to determine increases of eumelanin expression in seven, "normal volunteers" for Melanotan published in 2000 concluded that, "results show that the tanning induced by Melanotan in the face and forearm is associated with a significant increase in the eumelanin content of the human skin." [7]
A Phase II clinical human trial study conducted in 2003 at the University of Sydney demonstrated in a group of eighty volunteers that Melanotan caused a highly significant increase in skin-melanin. It found fairer-skin people (Fitzpatrick Types I/II, those who never tan and only burn and those who can tan in a limited fashion) recorded increases in melanin of up to 100% in some areas and that sunburn injury was reduced by more than 50% in fair skinned volunteers. [8][9]
Melanotan II
Melanotan II has tanning and aphrodisiac properties. [10][11]
It is a cyclic lactam analog of alpha-MSH with the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2.
A pilot Phase I clinical trial conducted on three males by the College of Medicine, Pharmacology Department, University of Arizona in Tucson, Arizona published in 1996 demonstrated that, "Melanotan II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection." The side effects reported were mild nausea and a "stretching and yawning complex" that correlated with spontaneous penile erections. [12]
A clinical study published in 2000 of 20 men with psychogenic and organic erectile dysfunction conducted at the Section of Urology of The University of Arizona College of Medicine concluded, "that Melanotan II is a potent initiator of penile erection in men with erectile dysfunction." [13]
Bremelanotide
Palatin Technologies developed another hormone originally targeted towards sexual dysfunction based upon melanotan II called bremelanotide (formerly PT-141). Bremelanotide is a metabolite of melanotan II that lacks the C-terminal amide function. In 2008, development for sexual dysfunction was discontinued after concerns were raised by the U.S. Food and Drug Administration (FDA) about the adverse side effect of increased blood pressure found in Phase II clinical trials. Concurrently the company announced plans to develop it as a treatment for hemorrhagic shock instead. [14]
Drug agency warnings
In 2007, the FDA issued a warning to an American vendor illegally marketing melanotan II on the internet as a drug that prevents skin cancer and assists tanning. The FDA has not licensed melanotan II, and explained: "There is no evidence that the product is generally recognized as safe and effective [GRAS/E] for its labeled uses." [15]
On August 8, 2008 the Danish Medicines Agency (DMA) issued a warning[16] against the usage of Melanotan purchased on the internet, noting that claims that imply that it has an, "effect" for protection against skin cancer, "has not been documented". The DMA further warned that Melanotan has not undergone tests for its effect and possible side effects, and that it is not licensed for usage in the EU or the USA.
References
- ^ "The Dark Side of Beauty Pills" (HTML). MSN.com. 2008. Retrieved 2008-08-21.
- ^ "UA-developed synthetic hormones speed a tan" (HTML). Arizona Daily Star. 2006. Retrieved 2007-09-22.
- ^ "The Barbie Drug" (HTML,WMV). Campbell Live, TV3. 2007. Retrieved 2007-09-16.
- ^ "Competitive Technologies Licenses Additional Patent to Melanotan Corporation, Receives Additional Shares of Epitan" (HTML). Business Wire. 2005. Retrieved 2008-08-22.
- ^ "World Health Organisation assigns CUV1647 generic name" (PDF). Clinuvel. 2008. Retrieved 2008-06-17.
- ^ "Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin" (HTML). Vol. 266 No. 19, November 20, 1991. Journal of the American Medical Association. 1991. Retrieved 2008-10-13.
- ^ "Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-alpha-MSH in humans" (HTML). Volume 72 Issue 4, Pages 526 - 532. Photochemistry and Photobiology. 2000. Retrieved 2008-10-13.
- ^ "Suntan could come 'in an implant'" (HTML). BBC News. 2003. Retrieved 2008-10-12.
- ^ "Sunburn Trial Results Show Drug Can Reduce Sun Damage by 50% for Fair-Skinned People, says Trial Head" (HTML). innovations report. 2003. Retrieved 2008-08-22.
- ^ "CNN.com "Tanning drug may find new life as Viagra alternative"" (HTML). CNN. 1999. Retrieved 2008-06-12.
- ^ "Tanning Bonus" (HTML). Time. 1999. Retrieved 2008-09-17.
- ^ "Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study" (HTML). Life Sciences, Volume 58, Issue 20, 12 April 1996, Pages 1777-1784. Elsevier Science Inc. 1996.
- ^ "Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II" (HTML). 12, Suppl 4, S74-S79. International Journal of Impotence Research. 2000.
- ^ "Palatin Technologies announces new strategic objectives and reports third quarter 2008 financial results" (HTML). Palatin Technologies. 2008. Retrieved 2008-08-21.
- ^ "FDA Warns About Unapproved Product, Melanotan II" (HTML). U.S. Food and Drug Administration. 2007. Retrieved 2008-08-21.
- ^ "Warning against the product Melanotan" (HTML). Danish Medicines Agency. 2008. Retrieved 2008-08-11.