Melanotan 2 (10mg)

Description

Guide to Melanotan 2 Research

Peptides such as Melanotan 2 (or Melanotan II) is said to help prevent skin cancer that is induced by sunlight. These peptides usually govern by stimulating the skin tanning process post intake (2).

Tanning is a common process where the skin is darkened due to exposure to the ultraviolet (UV) rays, which is either via direct sunlight or from artificial sources such as the tanning lamp. People sometimes intentionally tan their skin via sunbathing or use chemicals to produce a tanning effect.

Short reasonable exposure to ultraviolet rays can be beneficial as a natural source of Vitamin D. However, excessive exposure may lead to serious damage such as skin cancer (1).

What is Melanotan 2?

Melanotan 2 peptide is a synthetic compound, which is an analogue of the human hormone, also known as α-melanocyte-stimulating hormone (2).

The peptide is a cyclic heptapeptide that is similar to the human hormone, which primarily stimulates the process of melanogenesis in the human body i.e., formation of melanin. Interestingly, the peptide also induces sexual arousal and excitement in humans, similar to the α-melanocyte-stimulating hormone (MSH)(2). This mechanism is further described in the article.

Melanotan 2 History

During the research in early 1960s (3), melanotropic ligands, i.e., α-melanocyte-stimulating hormone (analogous to Melanotan II), were administered in the rats to understand their role and mechanism. During this research, while examining the rats, it was also accidentally discovered that these chemicals also induced sexual arousal, along with melanogenesis.

Continued research in the mid-20th century also resulted in similar outcomes. In this study (4), several varieties of the mammalian species were administered with the peptide via intracerebral route of administration. Results demonstrated similar effects of sexual excitement in all these species.

It was not until the 1980s that interest rose in using the MSH analogs in humans for treating sexual dysfunction and erectile dysfunction.

During the mid-1980s research (4), after synthesis of the Melanotan 2 peptide, a scientist, who voluntarily wanted to test the drug on himself, inadvertently administered himself with twice the amount of the intended dose. As a result, he experienced an 8-hour long erection, along with continued nausea and vomiting.

As a result of this outcome, it garnered interest to use the peptide to treat sexual problems in males. Further studies to be conducted to understand the mechanism of action of peptide, which induced two diverse effects of melanogenesis and penile erection.

Melanotan 2 Mechanism of action

Melanotan II serves as a non-selective agonist and has the ability to bind with five different melanocortin receptor subtypes (MC-R) located at five different locations. Depending on the localization, the receptor-Melanotan II bond will induce different effects.

MC1-R and MC2-R, located on the skin and adrenal cortex, are melanocytic in nature. Once Melanotan II binds with these receptors, it would stimulate them and induce melanocytes in the skin. This event, thereby, leads to increased production of eumelanin, which causes skin tanning (5).

MC3-R is located in the brain and digestive tract. While MC5-R is found in the endocrine and exocrine glands. Binding to these receptors leads to the adverse effects such as flushing, dizziness, anxiety, stomach ache, decreased appetite, and constipation (5).

MC4-R is located in the central nervous system. When Melanotan binds with this receptor, it induces the supraspinal centers in the brain, which leads to increased sexual desire and libido. These signals are then carried to the sympathetic and parasympathetic centers in the spinal cord and thoracolumbar region. These regions, that otherwise stimulate the vascular tone in the penile tissues, will get stimulated and thereby lead to penile erection (4).

Melanotan II Benefits

Below are the main advantages of the peptide (6):

• Erectile dysfunction therapy (or ED therapy)
• Skin tanning
• Probable skin cancer prevention
• Rosacea
• Fibromyalgia

While there are studies confirming the positive effects of the peptide, there is also evidence that the peptide causes some serious side effects. The peptide is now marketed only as a non-regulated product (6). This is described further below.

Research and Clinical Studies

Melanotan Studies as Potential Skin Cancer Preventative peptide

In this study (7), rats were orally administered with the Melanotan 2 peptide.

After the treatment, potentiometric titration and UV spectrophotometry were conducted to determine the dissociation constants of the compound. The pharmacokinetic results were 6.54 (with histidine) and 11.72 (with arginine) respectively. Whereas the bioavailability in the rat was determined to be 4.6% in rats.

These results indicated that the peptide can be a suitable candidate to potentially diagnose and prevent skin cancer in humans, though additional studies would be required.

Melanotan 2 Effects in Nerve Regeneration and Neuroprotection:

In this study(8), a rodent model was used which had induced peripheral nerve injury. This model was chosen in order to investigate the neurotrophic effects of the compound. The rodents were administered with different doses of 2 microg/kg body weight, 20 micro/kg body weight and 50 microg/kg body weight subcutaneously.

48 hours after the treatment, it was noted that the Melanotan 2 treated rodents demonstrated significant recovery in their sensory function. However, it should be noted that this outcome was noted only at the dose of 20 microg/kg and not the other two doses.

Furthermore, when the rodents were treated with cisplatin, a chemotherapeutic medication, Melanotan 2 demonstrated neuroprotective properties and protected the nerves from cisplatin induced neurotoxicity, up to a certain extent.

These studies demonstrated that the peptide exhibited additional benefits that could potentially be used for certain neuro treatments in humans.

Human Studies with Melanotan 2 as Sexual Stimulant

In this study (9), 20 men with organic erectile dysfunction were administered with Melanotan 2 via a double blinded placebo-controlled study in doses of 0.025 mg/kg body weight.

After the treatment, penile rigidity was monitored for a period of 6 hours. After the study, it was noted that 17 out of 20 men experienced penile erection. Moreover, 13 out of 20 men experienced elevated sexual desire, whereas only 4 men experienced sexual desire when treated with placebo.

There were, however, side effects noted during this study as well – common ones being yawning and vomiting. Severe nausea was experienced in 13% of the subjects.

These findings indicated that, despite the severe gastrointestinal disturbances, Melanotan 2 could be a potent candidate to treat erectile dysfunction.

Side Effects

Serious adverse events reported after the use of Melanotan:

Melanoma

A 20-year-old woman suffering from Fitzpatrick skin type II visited a dermatologist, who, upon clinical examination, noticed a black, melanocytic lesion on her skin. Beyond that, her skin was intensely pigmented. Upon histological examination, she was diagnosed with melanoma.

Upon investigation, it was discovered that the patient had self-administered Melanotan 2 for 3 to 4 weeks, which could have possibly led to this severe adverse event.

The above incident (10) drew attention to the potential severe risks associated with the peptide use.

Renal Infarction

Several research studies (11) have demonstrated that excessive use of Melanotan II induces renal infarction and kidney damage. It is understood that Melanotan II causes thrombotic and toxic effects on the renal parenchyma, which then potentially leads to severe renal injury.

Excessive Dosing led to systemic toxicity and rhabdomyolysis

A 39-year-old male purchased Melanotan 2 via the internet and self-administered 6 mg of the peptide via subcutaneous route. Two hours after the administration, he visited the emergency center complaining about severe body aches, perspiration, and anxiety. Upon examination, it was noted that all his vital signs were highly elevated and renal test results were completely off. He was then diagnosed with rhabdomyolysis (12).

Below are the other common side effects experienced with this peptide:

• Pain, redness, and inflammation at the site of injection (most common)
• Itchiness
• Headache
• Dizziness, flushing
• Nausea
• Yawning
• Stomach ache
• Reduced appetite

Different formulations of Melanotan products

Melanotan products are currently available for purchase on the internet in three main forms – Melanotan 1, Melanotan 2 and Bremelanotide (or PT 141) (12,13).

Each Melanotan formulation is associated with a specific use and stimulates specific responses in the body.

Melanotan 1 (or Melanotan I) is primarily used to induce melanogenesis and stimulate melanin production in the human body leading to skin tan.

Melanotan 2 (or Melanotan II) leads to both skin tan and spontaneous penile erections and sexual arousal.

Bremelanotide/PT 141 is a modified version of Melanotan 2 (where one of the chemical groups in the compound is replaced) and is specially designed for sexual stimulation.

Is it clinically approved?

Initial clinical trials (Phase I) were conducted in human volunteers, as described above.

Further clinical trials (Phase II) studies were then planned to be conducted in male volunteers with sexual dysfunction, where the peptide was to be administered both subcutaneously and transmucosally. However, these studies were discontinued as of 2003. No further results have been available since then (14).

Issuance of FDA Warning Letter

In 2007, the US FDA issued a warning letter to the manufacturer of Melanotan 2 peptide for the illegal sale and marketing of the product that was not FDA approved.

The manufacturer promoted the product on their website as ‘an injectable tanning product that would also prevent skin cancer and rosacea.’

However, this medication had not been approved by the FDA then and was being mislabeled and sold illegally. FDA had warned people to avoid administering any non-FDA approved medication, including Melanotan II (15).

Summary

Melanotan 2 is a synthetic cyclic heptapeptide, which is similar to a human hormone called α-melanocyte-stimulating hormone (MSH).

Melanotan 2 is non-selective agonistic in nature due to which it can bind with five different kinds of melanocortin receptor subtypes. As a result of this, it can induce varied effects in the human body, both good and bad.

While initially thought to primarily possess skin tanning effects, and thereby prevent skin cancer induced by excessive exposure to sunlight, it was accidentally discovered that the peptide also has additional pharmacological effects, mainly elevated sexual arousal and penile erection.

However, upon many research studies it was discovered that the peptide caused some serious side effects, with known events of peptide induced melanoma, systemic toxicity, and renal damage.

Research studies have been conducted on rodents and clinical trials (Phase I) were conducted on human volunteers. However, due to serious adverse events and associated health risks, Phase II clinical trials were discontinued in 2003 and since then no results are available.

It should be noted that unregulated products of Melanotan 2 are currently being sold on the internet as skin-tanning products. Users of these medications are at a high risk of being exposed to potential harms, if used excessively (16).

References:

1. Ultraviolet (UV) Radiation, American Cancer Society. https://www.cancer.org/cancer/cancer-causes/radiation-exposure/uv-radiation.html

2. Ryakhovsky, Vladimir V et al. “The first preparative solution phase synthesis of melanotan II.” Beilstein journal of organic chemistry vol. 4 (2008): 39. doi:10.3762/bjoc.4.39. https://pubmed.ncbi.nlm.nih.gov/19043625/

3. Mac E. Hadley, Discovery that a melanocortin regulates sexual functions in male and female humans, Peptides, Volume 26, Issue 10, 2005, Pages 1687-1689, ISSN 0196-9781, https://doi.org/10.1016/j.peptides.2005.01.023

4. King, Stephen H et al. “Melanocortin receptors, melanotropic peptides and penile erection.” Current topics in medicinal chemistry vol. 7,11 (2007): 1098-1106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694735/

5. Peters, Björn et al. “Melanotan II: a possible cause of renal infarction: review of the literature and case report.” CEN case reports vol. 9,2 (2020): 159-161. doi:10.1007/s13730-020-00447-z. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148395/

6. Melanotan, Vitamin and Supplements. https://www.webmd.com/vitamins/ai/ingredientmono-884/melanotan

7. Lan, E L et al. “Preformulation studies with melanotan-II: a potential skin cancer chemopreventive peptide.” Journal of pharmaceutical sciences vol. 83,8 (1994): 1081-4. doi:10.1002/jps.2600830805. https://pubmed.ncbi.nlm.nih.gov/7983590/

8. Ter Laak, Mariël P et al. “The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat.” European journal of pharmacology vol. 462,1-3 (2003): 179-83. doi:10.1016/s0014-2999(02)02945-x. https://pubmed.ncbi.nlm.nih.gov/12591111/

9. Wessells, H et al. “Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.” International journal of impotence research vol. 12 Suppl 4 (2000): S74-9. doi:10.1038/sj.ijir.3900582. https://pubmed.ncbi.nlm.nih.gov/11035391/

10. Hjuler, Kasper Fjellhaugen, and Henrik Frank Lorentzen. “Melanoma associated with the use of melanotan-II.” Dermatology (Basel, Switzerland) vol. 228,1 (2014): 34-6. doi:10.1159/000356389. https://pubmed.ncbi.nlm.nih.gov/24355990/

11. Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020 May;9(2):159-161. doi: 10.1007/s13730-020-00447-z. Epub 2020 Jan 18. PMID: 31953620; PMCID: PMC7148395. https://pubmed.ncbi.nlm.nih.gov/31953620/

12. John Devlin, Adam Pomerleau, Jenelle Foote. (2013) Melanotan II overdose associated with priapism. Clinical Toxicology 51:4, pages 383-383. https://www.tandfonline.com/doi/full/10.3109/15563650.2012.740637

13. Nelson, Michael E et al. “Melanotan II injection resulting in systemic toxicity and rhabdomyolysis.” Clinical toxicology (Philadelphia, Pa.) vol. 50,10 (2012): 1169-73. doi:10.3109/15563650.2012.740637. https://pubmed.ncbi.nlm.nih.gov/23121206/

14. Drug Profile: Melanotan II https://adisinsight.springer.com/drugs/800010143

15. FDA warns against using Melanotan II https://www.upi.com/Science_News/2007/09/05/FDA-warns-against-using-Melanotan-II/44981189007945/

16. Breindahl, Torben et al. “Identification and characterization by LC-UV-MS/MS of Melanotan II skin-tanning products sold illegally on the Internet.” Drug testing and analysis vol. 7,2 (2015): 164-72. doi:10.1002/dta.1655. https://pubmed.ncbi.nlm.nih.gov/24771717/

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Synonyms/Aliases: Melanotan 2, melanotan II, melanotan ii, MT2, MT-2

 

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