Melanotan II
Encyclopedia
- Note: this article describes melanotan II which should not be confused with melanotan-1 which is also known by the generic name afamelanotideAfamelanotideAfamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
.
Melanotan II developed at the University of Arizona
University of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...
is a synthetic
Peptide synthesis
In organic chemistry, peptide synthesis is the production of peptides, which are organic compounds in which multiple amino acids are linked via amide bonds which are also known as peptide bonds...
analog
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of the naturally occurring melanocortin
Melanocortin
The melanocortins are a group of peptide hormones which include adrenocorticotropic hormone and the different forms of melanocyte-stimulating hormone . They can be synthetic . In humans they can be endogenously produced from proopiomelanocortin in the pituitary gland...
peptide hormone
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
alpha-melanocyte stimulating hormone
Melanocyte-stimulating hormone
The melanocyte-stimulating hormones are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland...
(α-MSH) that in usage has been shown to have melanogenesis (tanning) and aphrodisiac
Aphrodisiac
An aphrodisiac is a substance that increases sexual desire. The name comes from Aphrodite, the Greek goddess of sexuality and love. Throughout history, many foods, drinks, and behaviors have had a reputation for making sex more attainable and/or pleasurable...
effects in preliminary studies and clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. It is a cyclic lactam
Lactam
A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
analog of α-MSH with the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2.
As of 2010 no compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
incorporating the melanotan II peptide has ever been approved for use
Regulation of therapeutic goods
The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency...
by any governmental drug regulatory bodies outside of clinical trials. Unlicensed and untested powders sold as "melanotan II" are found on the Internet and are reported to be used by thousands of members of the general public. Multiple regulatory bodies have warned consumers the peptides may be unsafe and ineffective in usage with one regulatory agency warning that consumers who purchase any product labeled "melanotan" risk buying a counterfeit drug. Medical researchers and Clinuvel Pharmaceuticals, the company developing the related peptide afamelanotide
Afamelanotide
Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
, has warned consumers that counterfeit products sold using the names "melanotan I and II", "pose a hazard to public health".
Historical development
Melanotan II was first synthesized at the University of ArizonaUniversity of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...
. Researchers there knew that one of the best defenses against skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
was melanin activated in the skin, a tan. They hypothesized
Hypothesis
A hypothesis is a proposed explanation for a phenomenon. The term derives from the Greek, ὑποτιθέναι – hypotithenai meaning "to put under" or "to suppose". For a hypothesis to be put forward as a scientific hypothesis, the scientific method requires that one can test it...
that an effective way to reduce skin cancer rates in people would be to induce the body's natural pigmentary system to produce a protective tan prior to UV exposure. The body's naturally occurring hormone α-MSH causes melanogenesis, a process by which the skin's pigment cells (melanocyte
Melanocyte
-External links: - "Eye: fovea, RPE" - "Integument: pigmented skin"...
s) produce the skin's pigment (melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
). They tested to see if administering this endogenous hormone to the body directly could be an effective method to cause sunless tanning
Sunless tanning
Sunless tanning Sunless tanning Sunless tanning (also known as UV-free tanning, self tanning, spray tanning (when applied topical, or fake tanning) refers to the application of chemicals to the skin to produce an effect similar in appearance to a suntan...
. What they found was that while it appeared to work, natural α-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 Victor J. Hruby and Mac E. Hadley, found a peptide, [Nle4, D-Phe7]-α-MSH, that was approximately 1,000 times more potent than natural α-MSH. They dubbed this new peptide molecule, "Melanotan" (later Melanotan-1, now known as afamelanotide
Afamelanotide
Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
). They subsequently developed another analog, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2), which they called "Melanotan II". The scientists hoped to use these peptides to combat melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
by stimulating the body's natural pigmentary mechanism to create a tan without first needing exposure to harmful levels of UV radiation. 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
Technology transfer
Technology Transfer, also called Transfer of Technology and Technology Commercialisation, is the process of skill transferring, knowledge, technologies, methods of manufacturing, samples of manufacturing and facilities among governments or universities and other institutions to ensure that...
company, to a number of biotechnology companies who intend to develop them into drugs.
Human clinical trials
A pilot Phase I clinical trial conducted on three males by the College of MedicineMedical school
A medical school is a tertiary educational institution—or part of such an institution—that teaches medicine. Degree programs offered at medical schools often include Doctor of Osteopathic Medicine, Bachelor/Doctor of Medicine, Doctor of Philosophy, master's degree, or other post-secondary...
, Pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
Department, University of Arizona
University of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...
in Tucson, Arizona
Tucson, Arizona
Tucson is a city in and the county seat of Pima County, Arizona, United States. The city is located 118 miles southeast of Phoenix and 60 miles north of the U.S.-Mexico border. The 2010 United States Census puts the city's population at 520,116 with a metropolitan area population at 1,020,200...
published in 1996 reported 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 erection
Erection
Penile erection is a physiological phenomenon where the penis becomes enlarged and firm. Penile erection is the result of a complex interaction of psychological, neural, vascular and endocrine factors, and is usually, though not exclusively, associated with sexual arousal...
s.
The Department of Pharmacology, University of Arizona College of Medicine published a study in 1998 that involved ten men who suffered from psychogenic
Psychogenic disease
A psychogenic disease is a set of symptoms or complaints whose origin likely lies within the complex interactions of the frontal lobes of the brain and the system in which the complaint manifests...
erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
. Their trial concluded that, "Melanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dose of 0.025 mg./kg."
A clinical study published in 2000 of 20 men with psychogenic and organic erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
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."
General population usage of melanotan peptides
General public users of the melanotan peptides have been reported to number into the thousands with one BBC report explaining that a January 2009 straw pollStraw poll
A straw poll or straw vote is a vote with nonbinding results. Straw polls provide dialogue among movements within large groups, reflecting trends like organization and motivation...
by the reporting journalist
Journalist
A journalist collects and distributes news and other information. A journalist's work is referred to as journalism.A reporter is a type of journalist who researchs, writes, and reports on information to be presented in mass media, including print media , electronic media , and digital media A...
of just 6 UK needle exchanges
Needle-exchange programme
A Needle & syringe programme or syringe-exchange programme is a social policy based on the philosophy of harm reduction where injecting drug users can obtain hypodermic needles and associated injection equipment at little or no cost. Many programmes are called "exchanges" because some require...
revealed, "nearly 500 people wanting the syringes [for peptide usage] or information about melanotan". Academic researchers have reported on a "thriving" internet community of users of the peptides at the site Melanotan.org where members discuss their experiences using the unlicensed and unregulated drugs. The site was reported to number more than 5,000 members as of February 2009. A January 2009 report in Wired Science described the site's forum as having more than 50,000 posts primarily covering "Usage and Experimentation" by members with many covering detailed regimens on how to attain skin darkening and/or sexual function [with Melanotan II] improvements.
In May 2010 the Norwegian tabloid daily Verdens Gang
Verdens Gang
Verdens Gang , generally known under the abbreviation VG, is a Norwegian tabloid newspaper...
published a story based upon a report by the Norwegian Pharmacy Association stating that 10,000 syringes are sold annually to Norwegian users of melanotan-1 and melanotan II.
"Melanotan" products sold for human use
A number of products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" which purport to have the same chemical make up as afamelanotide, of which the visual effect resulting from usage has been noted in an article by Wired.comWired News
Wired News is an online technology news website, formerly known as HotWired, that split off from Wired magazine when the magazine was purchased by Condé Nast Publishing in the 1990s. Wired News was owned by Lycos not long after the split, until Condé Nast purchased Wired News on July 11, 2006...
as being "eerily similar to results obtained in trials at the University of Arizona or by Clinuvel [An Australian company trialing the related afamelanotide
Afamelanotide
Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
peptide]". The Wired.com article explained that these products were Melanotan II, "a similar (but not identical) compound" and Clinuvel has stated that products sold as "melanotan" are "illegal" and "wholly unrelated to Clinuvel's proprietary afamelanotide". Chemicals sold as "melanotan" are not illegal to import
Import
The term import is derived from the conceptual meaning as to bring in the goods and services into the port of a country. The buyer of such goods and services is referred to an "importer" who is based in the country of import whereas the overseas based seller is referred to as an "exporter". Thus...
, use or own, however their domestic
Domestic policy
Domestic policy, also known as public policy, presents decisions, laws, and programs made by the government which are directly related to all issues and activity within the country....
sales (non-export
Export
The term export is derived from the conceptual meaning as to ship the goods and services out of the port of a country. The seller of such goods and services is referred to as an "exporter" who is based in the country of export whereas the overseas based buyer is referred to as an "importer"...
) and supply for human use outside of government sanctioned clinical trials is illegal within the boundaries of most jurisdictions, including the UK, USA, Europe and Australia.
A 2009 paper on unlicensed "melanotan" products, sold on the internet, has reported that the products caused moles to darken and increase in size over a short period, "an early warning sign of skin cancer". Academic researchers
Academia
Academia is the community of students and scholars engaged in higher education and research.-Etymology:The word comes from the akademeia in ancient Greece. Outside the city walls of Athens, the gymnasium was made famous by Plato as a center of learning...
at Liverpool John Moores University
Liverpool John Moores University
Liverpool John Moores University is a British 'modern' university located in the city of Liverpool, England. The university is named after John Moores and was previously called Liverpool Mechanics' School of Arts and later Liverpool Polytechnic before gaining university status in 1992, thus...
specialized in performance-enhancing drugs
Performance-enhancing drugs
Performance-enhancing drugs are substances used by athletes to improve their performances in the sports in which they engage.- Types of performance-enhancing drugs :...
published an editorial
Editorial
An opinion piece is an article, published in a newspaper or magazine, that mainly reflects the author's opinion about the subject. Opinion pieces are featured in many periodicals.-Editorials:...
in the British Medical Journal
BMJ
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
suggesting that use of 'melanotan I and II', "could damage the immune and cardiovascular systems as well as triggering other problems".
Health warnings on "melanotan" products sold for human use
In 2007, the FDA issued a Warning LetterFDA Warning Letter
The United States Food and Drug Adminstration defines a Warning Letter as "...a correspondence that notifies regulated industry about violations that FDA has documented during its inspections or investigations...
to an American online 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
Generally recognized as safe and effective
Generally recognized as safe and effective is a legal term used to describe certain old drugs that do not require prior approval from the U.S...
[GRAS/E] for its labeled uses." The FDA concurrently gave a blanket warning advising consumers to, "stop using Melanotan II, an unapproved product".
On August 8, 2008 the Danish Medicines Agency
Danish Medicines Agency
The Danish Medicines Agency is an agency under the Danish Ministry of Health and Prevention.The purpose of the agency is to ensure that medicinal products used in Denmark are of satisfactory quality, are safe to use and that they have the desired effect...
(DMA) issued a warning against the usage of any product called "Melanotan" purchased on the internet, noting that claims that imply that it has an, "effect" for protection against skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
, "has not been documented". The DMA further warned that Melanotan has not undergone tests for its effect and possible side effects, and is an "illegal medicinal product" that it is not licensed for usage in the EU
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
or the USA.
The UK Medicines and Healthcare products Regulatory Agency
Medicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
issued a similar warning on November 17, 2008 stating that "We are warning people not to use this product. Don’t be fooled into thinking that Melanotan offers a shortcut to a safer and more even tan. The safety of these products is unknown and they are unlicensed in the UK. The side effects could be extremely serious. If you have used either of these products do not use them again and if you have any concerns you should seek advice from your doctor.”
The FDA issued a warning letter to another online vendor in January 2009 selling "10 MG MT 2 [Melanotan II] -American Lab" as advertisements of the products on their website were in breach of the Federal Food, Drug, and Cosmetic Act
Federal Food, Drug, and Cosmetic Act
The United States Federal Food, Drug, and Cosmetic Act , is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration to oversee the safety of food, drugs, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from...
as the site was selling "new drug" products "intended for human use".
The Irish Medicines Board (IMB) issued a precautionary safety alert on February 27, 2009 regarding the use of "the unauthorised medicine Melanotan (I and II)", sold as a powder for injection, stating that "Melanotan is not authorised in Ireland and therefore the IMB cannot guarantee the efficacy, safety or quality of this product." In its release, the IMB announced that its tests had found the presence of microbial contamination in a vial of water sold together with melanotan powder which "would expose recipients to a risk of serious infection".
The Norwegian Medicines Agency
Norwegian Medicines Agency
The Norwegian Medicines Agency is the national, regulatory authority for new and existing medicines and the supply chain. The Agency is responsible for supervising the production, trials and marketing of medicines. It approves medicines and monitors their use, and ensures cost-efficient, effective...
has issued warnings in 2007 and 2009 about the use of "Melanotan" sold online, while a spokesman for the Australian Therapeutic Goods Administration
Therapeutic Goods Administration
The Therapeutic Goods Administration is the regulatory body for therapeutic goods in Australia . It is a Division of the Australian Department of Health and Ageing established under the Therapeutic Goods Act 1989 ...
warned consumers to be "very wary" of using it.
In late July 2010 the Swedish Medical Products Agency issued a warning against the usage of melanotan II.
Bremelanotide
Palatin Technologies developed another hormone targeted towards sexual dysfunctionSexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
therapy based upon melanotan II called bremelanotide (formerly PT-141). Bremelanotide is a metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of melanotan II that lacks the C-terminal amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
function
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
. The drug has been undergoing clinical trials for the treatment of sexual arousal disorder
Sexual arousal disorder
Sexual arousal disorder is characterized by a lack or absence of sexual fantasies and desire for sexual activity in a situation that would normally produce sexual arousal, or the inability to attain or maintain typical responses to sexual arousal. The disorder is found in the DSM-IV...
and erectile dysfunction. It is intended for both men and women. Preliminary results have proven the efficacy of this drug, however development was briefly suspended due to a side effect of increased blood pressure observed in a small number of trial subjects administered the drug intranasally. On August 12, 2009, Palatin announced positive results (none of the previous heightened blood pressure effects were observed) of a phase I clinical study where trial subjects were instead administered the drug subcutaneously. Palatin is concurrently developing a related compound they call PL-6983.
External links
- Melanotan.org
- PubChem entry Melanotan II
- PubChem entry rac-Melanotan II (racemic PhePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
)