Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Afamelanotide: Difference between pages

{{Short description|Chemical compound}}

{{Undisclosed paid|date=July 2018}}

{{tone|date=January 2020}}

{{Use dmy dates|date= January 2022}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477364562

| image = Melanotan.png

| width =

| alt =

| caption =

<!-- Clinical data -->

| pronounce = {{IPAc-en|audio=En-afamelanotide.oga|ˌ|æ|f|ə|m|ɛ|ˈ|l|æ|n|oʊ-|t|aɪ|d}}

| tradename = Scenesse

| Drugs.com = {{Drugs.com|monograph|afamelanotide-acetate-topical}}

| MedlinePlus =

| DailyMedID = Afamelanotide

| pregnancy_AU = B1

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]

| class =

| ATC_prefix = D02

| ATC_suffix = BB02

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref name="Scenesse FDA label">{{cite web | title=Scenesse- afamelanotide implant | work = DailyMed | publisher = U.S. National Library of Medicine | date=15 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48 | access-date=15 June 2023 | archive-date=25 July 2022 | archive-url=https://web.archive.org/web/20220725143050/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48 | url-status=live }}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Scenesse EPAR" />

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life = 30 minutes<ref name=EMA2017/>

| duration_of_action =

| excretion =

<!-- Identifiers -->

| index2_label = as salt

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 75921-69-6

| CAS_supplemental =

| PubChem = 16154396

| IUPHAR_ligand = 1324

| DrugBank_Ref =

| DrugBank = DB04931

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 17310725

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = QW68W3J66U

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D10511

| KEGG2_Ref = {{keggcite|changed|kegg}}

| IUPHAR_ligand2 =

| KEGG2 = D11334

| ChEBI = 136034

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 441738

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = [Nle⁴,<small>D</small>-Phe⁷]α-MSH; NDP-α-MSH; NDP-MSH; Melanotan; Melanotan-1; Melanotan I; EPT1647; CUV1647;

<!-- Chemical and physical data -->

| IUPAC_name = ''N''-acetyl-<small>L</small>-seryl-<small>L</small>-tyrosyl-<small>L</small>-seryl-<small>L</small>-norleucyl-<small>L</small>-α-glutamyl-<small>L</small>-histidyl-<small>D</small>-phenylalanyl-<small>L</small>-arginyl-<small>L</small>-tryptophylglycyl-<small>L</small>-lysyl-<small>L</small>-prolyl-<small>L</small>-valinamide

| C = 78

| H = 111

| N = 21

| O = 19

| SMILES = CCCCC(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CN=CN1)C(=O)NC(CC2=CC=CC=C2)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC3=CNC4=CC=CC=C43)C(=O)NCC(=O)NC(CCCCN)C(=O)N5CCCC5C(=O)NC(C(C)C)C(=O)N)NC(=O)C(CO)NC(=O)C(CC6=CC=C(C=C6)O)NC(=O)C(CO)NC(=O)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C78H111N21O19/c1-5-6-19-52(91-75(116)61(41-101)97-72(113)57(34-46-24-26-49(103)27-25-46)94-74(115)60(40-100)88-44(4)102)68(109)92-54(28-29-64(105)106)70(111)96-59(36-48-38-83-42-87-48)73(114)93-56(33-45-16-8-7-9-17-45)71(112)90-53(22-14-31-84-78(81)82)69(110)95-58(35-47-37-85-51-20-11-10-18-50(47)51)67(108)86-39-63(104)89-55(21-12-13-30-79)77(118)99-32-15-23-62(99)76(117)98-65(43(2)3)66(80)107/h7-11,16-18,20,24-27,37-38,42-43,52-62,65,85,100-101,103H,5-6,12-15,19,21-23,28-36,39-41,79H2,1-4H3,(H2,80,107)(H,83,87)(H,86,108)(H,88,102)(H,89,104)(H,90,112)(H,91,116)(H,92,109)(H,93,114)(H,94,115)(H,95,110)(H,96,111)(H,97,113)(H,98,117)(H,105,106)(H4,81,82,84)/t52-,53-,54-,55-,56+,57-,58-,59-,60-,61-,62-,65-/m0/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UAHFGYDRQSXQEB-LEBBXHLNSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

'''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]].<ref name="Scenesse FDA label" /><ref name="Scenesse EPAR" /><ref name="FDA Snapshot" /> It is a melanocortin 1 receptor (MC1-R) agonist<ref name="Scenesse FDA label" /> and a [[peptide synthesis|synthetic]] [[peptide]] and [[structural analog|analogue]] of [[α-melanocyte stimulating hormone]].<ref name="Scenesse FDA label" /> It is administered as subcutaneous implant.<ref name="EMA2017" />

The US [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref>{{cite web | title=New Drug Therapy Approvals 2019 | website=U.S. Food and Drug Administration | date=31 December 2019 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | access-date=15 September 2020 | archive-date=16 September 2020 | archive-url=https://web.archive.org/web/20200916144738/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | url-status=live }}</ref>

== Medical uses ==

In the European Union, afamelanotide is [[indicated]] for the prevention of phototoxicity in adults with erythropoietic protoporphyria.<ref name=EMA2017>{{cite web|title=Scenesse: Summary of Product Characteristics|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002548/WC500182307.pdf|publisher=[[European Medicines Agency]] (EMA)|date=27 January 2016|access-date=6 April 2017|archive-date=6 April 2017|archive-url=https://web.archive.org/web/20170406201555/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002548/WC500182307.pdf|url-status=live}}</ref><ref name="Scenesse EPAR">{{cite web | title=Scenesse EPAR | website=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse | archive-url=https://web.archive.org/web/20191119035520/https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse | archive-date=19 November 2019 | url-status=live | access-date=18 November 2019| date=17 September 2018 }}</ref>

In the United States, afamelanotide is [[indicated]] for increasing pain-free light exposure in adults with a history of reactions to light (phototoxicity) from erythropoietic protoporphyria.<ref name="Scenesse FDA label" />

==Adverse effects==

Very common adverse effects include [[nausea]] and headache (may affect more than 10% of people). Common adverse effects include injection site reactions, back pain, upper respiratory tract infections, [[Melanocytic nevus|melanocyte naevus]], decreased appetite, [[migraine]], dizziness, weakness, fatigue, lethargy, sleepiness, feeling hot, stomach pain, diarrhea, vomiting, flushing and red skin, development of warts, spots and freckles and itchy skin (between 1% and 10% of people). Uncommon and rare adverse effects include [[cystitis]], [[folliculitis]], gastrointestinal infections, hypersensitivity reactions, changes in appetite, depression, [[insomnia]], balance disorders, lethargy, [[Restless legs syndrome|restless leg syndrome]], [[Syncope (medicine)|syncope]], [[photophobia]], [[presbyopia]], [[tinnitus]], confusion, [[palpitations]], hypertension, [[Hypercholesterolemia|hypercholesterolaemia]] and weight gain.<ref name=EMA2017/>

==Pharmacology==

Afamelanotide is a synthetic [[tridecapeptide]] and a structural analogue of [[Alpha-Melanocyte-stimulating hormone|α-melanocyte stimulating hormone]] (α-MSH). It is a melanocortin receptor [[agonist]] and binds predominantly to the [[Melanocortin 1 receptor|melanocortin-1 receptor]] (MC1R). Its binding lasts longer than that of α-MSH. This results in part from afamelanotide's resistance to immediate degradation by serum or proteolytic enzymes. It is thought to cause skin darkening by binding to the [[melanocortin 1 receptor]] which in turn drives [[Melanocyte#Melanogenesis|melanogenesis]].<ref name=EMA2017/>

It has a short half-life of approximately 30 minutes. After administration with implantation into the skin, the majority of the drug is released within two days, with 90% released by the fifth day. By the tenth day, no drug is detectable in plasma.<ref name=EMA2017/>

Drug distribution, metabolism and excretion were not understood as of 2017.<ref name=EMA2017/>

==Chemistry==

Afamelanotide has the [[Peptide sequence|amino acid sequence]]; Ac-Ser-Tyr-Ser-Nle-Glu-His-<small>D</small>-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂.

It is also known as [Nle⁴,<small>D</small>-Phe⁷]-α-MSH, which is abbreviated to NDP-MSH or NDP-α-MSH.

Afamelanotide is the [[international nonproprietary name]].<ref>{{Cite web|url=https://www.who.int/medicines/publications/druginformation/innlists/PL100prepubli.pdf|title=International Nonproprietary Names for Pharmaceutical Substances (INN)|access-date=2 March 2009|publisher=[[World Health Organization]] (WHO)|year=2009|archive-date=14 April 2020|archive-url=https://web.archive.org/web/20200414173446/http://www.who.int/medicines/publications/druginformation/innlists/PL100prepubli.pdf|url-status=live}}</ref>

==History==

α-MSH was first isolated in the 1950s and its primary structure determined. By the 1960s, its role in promoting melanin diffusion was understood.<ref>{{cite journal | vauthors = Baker BI | title = The role of melanin-concentrating hormone in color change | journal = Annals of the New York Academy of Sciences | volume = 680 | issue = 1 | pages = 279–289 | date = May 1993 | pmid = 8390154 | doi = 10.1111/j.1749-6632.1993.tb19690.x | bibcode = 1993NYASA.680..279B | s2cid = 11465789 }}</ref>

In the 1980s, the University of Arizona synthesised more potent analogs of a-MSH, including afamelanotide. Afamelanotide was initially named melano-tan (or melanotan-I) due to its ability to tan skin with minimal sun exposure. Later, melanotan-II was synthesised.<ref>{{cite journal | vauthors = Sawyer TK, Sanfilippo PJ, Hruby VJ, Engel MH, Heward CB, Burnett JB, Hadley ME | title = 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 10 | pages = 5754–5758 | date = October 1980 | pmid = 6777774 | pmc = 350149 | doi = 10.1073/pnas.77.10.5754 | doi-access = free | bibcode = 1980PNAS...77.5754S }}</ref><ref>{{Cite thesis | vauthors = Lan EL | degree = Ph.D. |date=1992 |title=Preformulation studies of melanotan-II |url= https://repository.arizona.edu/bitstream/handle/10150/291574/azu_td_1350780_sip1_w.pdf| publisher = [[University of Arizona]]|access-date=16 April 2021|archive-date=16 April 2021|archive-url=https://web.archive.org/web/20210416170542/https://repository.arizona.edu/bitstream/handle/10150/291574/azu_td_1350780_sip1_w.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ | title = Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics | journal = Journal of Medicinal Chemistry | volume = 32 | issue = 12 | pages = 2555–2561 | date = December 1989 | pmid = 2555512 | doi = 10.1021/jm00132a010 }}</ref><ref name="HadleyDorr2006" />

Following initial [[drug development|development]] at the University of Arizona as a [[sunless tanning]] agent, the Australian company Clinuvel conducted further clinical trials in that and other indications, and brought the drug to market in the European Union, the United States, and Australia.

To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies, a [[technology transfer]] company operating on behalf of University of Arizona, to an Australian startup called Epitan,<ref name=PL2004>{{cite news|title=EpiTan focuses on Melanotan, a potential blockbuster|url=https://www.thepharmaletter.com/article/epitan-focuses-on-melanotan-a-potential-blockbuster|work=The Pharma Letter|date=1 November 2004|access-date=6 April 2017|archive-date=30 July 2018|archive-url=https://web.archive.org/web/20180730203014/https://www.thepharmaletter.com/article/epitan-focuses-on-melanotan-a-potential-blockbuster|url-status=live}}</ref><ref name=HadleyDorr2006>{{cite journal | vauthors = Hadley ME, Dorr RT | title = Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization | journal = Peptides | volume = 27 | issue = 4 | pages = 921–930 | date = April 2006 | pmid = 16412534 | doi = 10.1016/j.peptides.2005.01.029 | s2cid = 21025287 }}</ref> which changed its name to Clinuvel in 2006.<ref>{{cite news|title=Epitan changes name to Clinuvel, announces new clinical program|url=http://www.labonline.com.au/content/life-scientist/news/epitan-changes-name-to-clinuvel-announces-new-clinical-program-161764385|work=LabOnline|date=27 February 2006|access-date=6 April 2017|archive-date=2 December 2020|archive-url=https://web.archive.org/web/20201202114725/https://www.labonline.com.au/content/life-scientist/news/epitan-changes-name-to-clinuvel-announces-new-clinical-program-161764385|url-status=live}}</ref>

Early clinical trials showed that the peptide had to be injected about ten times a day due to its short half-life, so the company collaborated with [[Southern Research]] in the US to develop a [[Injection (medicine)#Depot|depot formulation]] that would be injected under the skin, and release the peptide slowly. This was done by 2004.<ref name=PL2004/>

As of 2010, afamelanotide was in Phase III trials for [[erythropoietic protoporphyria]] and [[polymorphous light eruption]] and was in Phase II trials for [[actinic keratosis]] and [[squamous cell carcinoma]]; as well, it had been trialled in [[phototoxicity]] associated with [[Biological system|systemic]] [[photodynamic therapy]] and [[solar urticaria]].<ref name=2010status>{{cite news| vauthors = Dean T |title=Biotechnology profile: Bright future for Clinuvel (ASX:CUV)|url=http://www.labonline.com.au/content/life-scientist/news/biotechnology-profile-bright-future-for-clinuvel-asx-cuv--837406981|work=Australian Life Scientist|date=3 May 2010|archive-url=https://web.archive.org/web/20170406064959/http://www.labonline.com.au/content/life-scientist/news/biotechnology-profile-bright-future-for-clinuvel-asx-cuv--837406981|archive-date=6 April 2017}}</ref> Clinuvel had also obtained [[orphan drug]] status for afamelanotide in the US and the EU by that time.<ref name=2010status/>

In May 2010, the Italian Medicines Agency (AIFA, or Agenzia Italiana del Farmaco) approved afamelanotide as a treatment for [[erythropoietic protoporphyria]].<ref name="GU">{{Cite news|url=http://www.ansa.it/web/notizie/rubriche/gazzettaufficiale/2010/05/17/visualizza_new.html_1793113900.html|title=Gazzetta Ufficiale: Sommario|access-date=17 May 2010|publisher=[[Agenzia Nazionale Stampa Associata]]|year=2010|archive-date=29 February 2012|archive-url=https://web.archive.org/web/20120229154853/http://www.ansa.it/web/notizie/rubriche/gazzettaufficiale/2010/05/17/visualizza_new.html_1793113900.html|url-status=live}}</ref>

In January 2015, afamelanotide was approved by the [[European Medicines Agency]] (EMA) for the treatment of phototoxicity in people with erythropoietic protoporphyria.<ref name=EMA2017/>

There were three trials that evaluated afamelanotide in those with erythropoietic protoporphyria.<ref name="FDA Snapshot" />

In Trial 1, subjects received afamelanotide or vehicle implant every two months and were followed for 180 days.<ref name="FDA Snapshot" /> Subjects recorded every day the number of hours spent in direct sunlight and whether they experienced any phototoxic pain that day.<ref name="FDA Snapshot" /> The trial measured the total number of hours over 180 days spent in direct sunlight between 10 am and 6 pm on days with no pain.<ref name="FDA Snapshot" />

In Trial 2, subjects received afamelanotide or vehicle implants every two months and were followed for 270 days.<ref name="FDA Snapshot" /> Subjects daily recorded the number of hours spent outdoors as well as whether "most of the day" was spent in direct sunlight, shade, or a combination of both, and whether they experienced any phototoxic pain that day.<ref name="FDA Snapshot" /> The trial measured the total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which "most of the day" was spent in direct sunlight.<ref name="FDA Snapshot" />

In Trial 3, subjects were randomized to receive a total of three afamelanotide or vehicle implants administered subcutaneously every two months and were followed for 180 days.<ref name="FDA Snapshot" /> Data from this trial were used primarily for assessment of side effects.<ref name="FDA Snapshot" />

The FDA approved afamelanotide based on evidence from three clinical trials (Trial 1/ NCT 01605136, Trial 2/ NCT00979745 and Trial 3/ NCT01097044) of 244 adults, 18–74 years of age with erythropoietic protoporphyria.<ref name="FDA Snapshot" /> The trials were conducted at 22 sites in the US and Europe.<ref name="FDA Snapshot" />

In October 2019, afamelanotide was approved by the US [[Food and Drug Administration]] (FDA) as a medicine to reduce pain caused by light exposure (particularly sunlight) as experienced by people with erythropoietic protoporphyria.<ref name=Oct2019FDA>{{cite press release |title=FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-increase-pain-free-light-exposure-patients-rare-disorder|date=8 October 2019|archive-url=https://web.archive.org/web/20191009122611/https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-increase-pain-free-light-exposure-patients-rare-disorder|archive-date=9 October 2019 |url-status=live}} {{PD-notice}}</ref><ref name="FDA Snapshot">{{cite web | title=Drug Trials Snapshots: Scenesse | website=U.S. [[Food and Drug Administration]] (FDA) | date=8 October 2019 | url=http://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-scenesse | access-date=26 January 2020 | archive-date=13 August 2020 | archive-url=https://web.archive.org/web/20200813023541/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-scenesse | url-status=live }} {{PD-notice}}</ref>

==Society and culture==

===Usage in general public===

A number of products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" which discuss afamelanotide in their marketing.<ref>{{Cite web|url=http://wcbstv.com/topstories/tanorexia.melanotan.self.2.1013828.html |publisher=[[WCBS-TV]], [[CBS]] |date=20 May 2009 |access-date=23 July 2009 |title=Believe It Or Not 'Tanorexia' A Very Real Problem |url-status=dead |archive-url=https://web.archive.org/web/20090521151930/http://wcbstv.com/topstories/tanorexia.melanotan.self.2.1013828.html |archive-date=21 May 2009 }}</ref><ref>{{Cite web|url=http://www.cosmopolitan.com.au/fool_gold.htm|date=14 June 2009|title=Fools Gold|access-date=25 July 2009|work=[[Cosmopolitan (magazine)|Cosmopolitan]] (Australia)|archive-date=12 September 2009|archive-url=https://web.archive.org/web/20090912150202/http://cosmopolitan.com.au/fool_gold.htm|url-status=dead}}</ref><ref name="Wired-01-09">{{Cite magazine|url=https://www.wired.com/wiredscience/2009/01/tan/|title=Suntan Drug Greenlighted for Trials|access-date=11 April 2009|magazine=[[Wired (magazine)|Wired]]|date=29 January 2009| vauthors = Madrigal A |archive-url=https://web.archive.org/web/20090505032522/http://www.wired.com/wiredscience/2009/01/tan/|archive-date=5 May 2009|url-status=live}}</ref>

Without a prescription, these drugs are not legally sold in many jurisdictions and are potentially dangerous.<ref name="HeraldSun">{{cite web | vauthors = Betts M |url= http://www.heraldsun.com.au/news/tanning-drug-a-health-risk/story-e6frf7jo-1225792923321|title=Tanning drug a health risk|access-date=31 October 2009|work=[[Herald Sun]]|date=31 October 2009|archive-date=29 December 2010|archive-url=https://web.archive.org/web/20101229052605/http://www.heraldsun.com.au/news/tanning-drug-a-health-risk/story-e6frf7jo-1225792923321|url-status=dead}}</ref><ref>{{cite journal | vauthors = Langan EA, Nie Z, Rhodes LE | title = Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'? | journal = The British Journal of Dermatology | volume = 163 | issue = 3 | pages = 451–455 | date = September 2010 | pmid = 20545686 | doi = 10.1111/j.1365-2133.2010.09891.x | s2cid = 8203334 }}</ref><ref>{{cite journal | vauthors = Langan EA, Ramlogan D, Jamieson LA, Rhodes LE | title = Change in moles linked to use of unlicensed "sun tan jab" | journal = BMJ | volume = 338 | pages = b277 | date = January 2009 | pmid = 19174439 | doi = 10.1136/bmj.b277 | s2cid = 27838904 }}</ref><ref>{{cite news|url=http://news.bbc.co.uk/2/hi/health/7895366.stm|title=Risky tan jab warnings 'ignored'|access-date=4 March 2009|publisher=[[BBC News Online]]|date=18 February 2009|archive-url=https://web.archive.org/web/20090221213602/http://news.bbc.co.uk/2/hi/health/7895366.stm|archive-date=21 February 2009|url-status=live}}</ref>

Starting in 2007, health agencies in various countries began issuing warnings against their use.<ref>{{Cite web|url=http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=13865|title=Warning against the product Melanotan|access-date=11 August 2008|publisher=[[Danish Medicines Agency]]|year=2008}}</ref><ref>{{Cite press release|url=http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON031009|title="Tan jab" is an unlicensed medicine and may not be safe|access-date=17 November 2008|publisher=[[Medicines and Healthcare products Regulatory Agency]] (MHRA)|year=2008|archive-url=http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON031009|archive-date=5 December 2014|url-status=dead}}</ref><ref>{{Cite web|url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm152426.htm|title= US Lab Research Inc Warning letter|access-date=23 July 2009|publisher=U.S. [[Food and Drug Administration]] (FDA)|date=29 January 2009| archive-url= https://web.archive.org/web/20090710061631/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm152426.htm| archive-date= 10 July 2009 | url-status= live}}</ref><ref name="IMB">{{Cite web|url=http://www.imb.ie/EN/Safety--Quality/Advisory-Warning--Recall-Notices/Human-Medicines/Melanotan-Powder-for-Injection-.aspx|title=Melanotan Powder for Injection|access-date=2 February 2009|publisher=[[Irish Medicines Board]]|year=2009|work=Notice Information: – Warning – 27 February 2009|archive-date=1 August 2013|archive-url=https://web.archive.org/web/20130801034045/http://www.imb.ie/EN/Safety--Quality/Advisory-Warning--Recall-Notices/Human-Medicines/Melanotan-Powder-for-Injection-.aspx|url-status=live}}</ref><ref>{{Cite web|url=http://www.slk.no/templates/InterPage____65110.aspx|title= Legemiddelverket advarer mot bruk av Melanotan | trans-title = The Norwegian Medicines Agency warns against the use of Melanotan | language = no |access-date=11 March 2009 |publisher=Norwegian Medicines Agency|date=13 December 2007| archive-url= https://web.archive.org/web/20090417045006/http://www.slk.no/templates/InterPage____65110.aspx| archive-date= 17 April 2009 | url-status= live}}</ref><ref name="NoMA">{{Cite web|url=http://www.slk.no/templates/InterPage____80434.aspx|title= Melanotan – farlig og ulovlig brunfarge | trans-title = Melanotan - dangerous and illegal tan | language = no |access-date=11 March 2009|publisher=[[Norwegian Medicines Agency]]|date=23 January 2009| archive-url= https://web.archive.org/web/20090417045159/http://www.slk.no/templates/InterPage____80434.aspx| archive-date= 17 April 2009 | url-status= live}}</ref>

== References ==

{{Reflist}}

{{Other dermatological preparations}}

{{Melanocortin receptor modulators}}

{{Portal bar | Medicine}}

[[Category:Melanocortin receptor agonists]]

[[Category:Orphan drugs]]

[[Category:Peptides]]