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Melanotan II Peptide therapy | Benefits, uses, and safety

Sponsored: Curious about Melanotan II peptide therapy? Then you’re in the right place.

Curious about Melanotan II peptide therapy? Then this is the right place.

Melanotan II is a synthetic peptide designed to mimic the biological activity of alpha-melanocyte stimulating hormone (alpha-MSH). It was initially developed as a sunless tanning agent, enabling users to tan their skin without harmful sun or UV exposure.

Since its discovery in the 1980s, melanotan II has been evaluated in multiple clinical trials for tanning and as a treatment for sexual dysfunction, and has been determined to be well tolerated with all side effects considered temporary and mild.

Melanotan II peptide therapy is most commonly administered via injection, yet intranasal formulations are also available for test subjects.

In this article, the researchers at Peptides.org provide a thorough overview of the uses and benefits of the melanotan II peptide, as well as a breakdown of published research findings, dosing protocols, and instructions for administration in research settings.

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(Peptides.org, sponsored) Melanotan II Peptide therapy: benefits, uses, and safety.

What is Melanotan II?

Melanotan II was developed in the 1980s by researchers at the University of Arizona. The team was focused on developing a more potent peptide for stimulating melanin production than the endogenous alpha-melanocyte stimulating hormone (alpha-MSH) [1].

The primary objective was to develop a compound capable of inducing a “therapeutic tan” that would allow users to get the skin protection offered by tanned skin without the need for prolonged sun or UV exposure, which comes with several health risks, especially for light-skinned individuals [2].

To achieve this goal, the researchers developed several synthetic peptides that were stripped-down versions of the naturally occurring alpha-MSH, which binds to melanin-producing skin cells called melanocytes, triggering melanin production and subsequent skin darkening [1, 3].

Several landmark papers were published in the 1980s describing a series of synthetic, ultrapotent melanotropic peptides [3, 4]. The two most promising of these synthetic peptides were aptly named melanotan I (MT-I) and melanotan II (MT-II), with both capable of inducing significantly higher melanin production than the natural hormone a-MSH in biochemical assays [4].

MT-I was the first synthetic melanotropic peptide to be evaluated in a clinical trial (1991) and successfully caused skin darkening without safety concerns [5]. Despite the initial success, researchers were interested in also evaluating MT-II, shown to be even more potent than MT-I and was easier to manufacture [2, 3].

MT-II was evaluated in a phase I clinical trial in 1996 and was similarly shown to safely cause skin darkening, but was also found to induce erections in all patients shortly after injection [2]. Researchers learned that the smaller size of the MT-II peptide allowed it to cross the blood-brain barrier, facilitating binding to melanocortin receptors in the brain controlling sexual arousal that were inaccessible to MT-I.

This serendipitous finding led researchers to shift the focus of MT-II development towards treatment of erectile dysfunction. Subsequently clinical trials showed that MT-II could successfully treat men with both psychogenic and organic erectile dysfunction [6, 7].

In light of these striking results, MT-II was licensed by Palatin Technologies, who made a small chemical modification to mimic a naturally occurring metabolite of MT-II, which was named PT-141 [8, 9].

PT-141 has since been approved by the United States Food and Drug Administration (FDA) for treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, and was assigned the generic name, bremelanotide [10]. Notably, MT-I has also received FDA approval for treatment of the skin disorder erythropoietic protoporphyria, and is also referred to by the generic name, afamelanotide [11].

What Does Melanotan II Do?

The synthetic MT-II peptide is a non-selective melanocortin agonist, and has been shown to bind to melanocortin receptors 1 (MCR1), 3 (MCR3), 4 (MCR4), and 5 (MCR5), and consequently modulate the biology controlled by those receptors [4].

In large part due to the development efforts by the team that discovered MT-II, the field has learned that the melanocortin system controls a wide range of physiological functions [4, 12, 13]. The most well-characterized effects of MT-II in humans are around tanning and sexual arousal.

The skin darkening effects caused by MT-II are caused by binding at MCR1 receptors in melanocytes, leading to melanogenesis and subsequent transportation of melanosomes (melanin-containing vesicles) to skin cells [3].

Interestingly, light-skinned and dark-skinned individuals have roughly equivalent amounts of melanocytes; what dictates the differences in skin color is the level of melanocyte activity and the specific type of melanin produced. Light-skinned individuals produce more pheomelanin, a yellow-red pigment, than eumelanin, a dark brown pigment, which is also more protective against UV damage [14].

MT-II works on both vectors, stimulating melanocyte activity and causing preferential synthesis of eumelanin over pheomelanin, allowing light-skinned individuals to not only achieve a desirable golden tan, but also significantly boost their skin’s protection against UV damage [3, 4].

The sexual arousal effects of MT-II are derived from binding at MCR3 and MCR4 in the brain and represent a distinct mechanism of action from the commonly prescribed phosphodiesterase 5 inhibitors (PDE5i) such as sildenafil/Viagra [12].

This same mechanism is responsible for increased sexual arousal in women, which was clinically demonstrated with the MT-II derived metabolite bremelanotide (PT-141) [12, 15]. Since bremelanotide (PT-141) is a naturally occurring metabolite of MT-II, clinical trial results of bremelanotide in women point to a similar set of benefits for MT-II in women [10].

Melanotan II Benefits | Clinical Trials and Research

Melanotan II has been formally evaluated in clinical trials for benefits around tanning and erectile dysfunction [2 ,6, 7]. However, research around melanocortins and MT-II remains an active area of investigation and there is a large and growing body of research that points to a wide range of additional physiological functions that MT-II can beneficially modulate.

In this section, we will highlight clinical trial results and relevant, peer-reviewed findings that will be of interest to researchers studying the melanocortin system and associated physiological functions:

Sunless tanning and skin protection

MT-II was evaluated in a phase I clinical trial in 1996 to determine whether it could safely cause skin darkening [2]. In the trial, all participants were observed to have statistically significant skin darkening following a two-week intermittent dosing protocol. All side effects were considered tolerable and related to dose.

Despite the acceptable safety profile, an additional and unexpected effect of MT-II was observed in the initial clinical trial, as all participants experienced erections following administration of the peptide. Given that the same research team had also successfully evaluated melanotan I (MT-I) in a clinical trial for tanning, no further clinical trials were performed on MT-II.

MT-I (generic name, bremelanotide) was eventually given FDA approval for treatment of the skin disorder erythropoietic protoporphyria, as it was found to be safe and well-tolerated [11]. Notably, MT-II works via an identical mechanism to MT-I, suggesting a similar safety profile around melanocyte activation [4].

Sexual health

The erection-inducing effects of MT-II observed in the initial phase I clinical trial led researchers to shift focus away from tanning applications and towards treatment of erectile dysfunction [6].

MT-II was first evaluated for the treatment of erectile dysfunction in a double-blind, placebo controlled crossover trial that included 10 men who had psychogenic erectile dysfunction, meaning that they were capable of producing erections in their sleep, but unable prior to sexual activity [6]. In this population, MT-II was able to produce erections in 8 out of 10 subjects.

MT-II was next evaluated in a double blind, placebo controlled crossover clinical trial that included men with organic erectile dysfunction (erectile dysfunction due to physical, rather than mental problems) [7]. In this trial, erections were induced in 12 of 19 injections of MT-II versus 1 of 21 injections of placebo, a striking result in an otherwise difficult to treat population of men.

Appetite and Metabolism

The beneficial effects of MT-II on appetite and metabolism are due to its binding to melanocortin receptors in the brain that control food intake and energy expenditure [16]. The relevance of the melanocortin system for body composition is underscored by the fact that mutations in the MCR3 and MCR4 receptors have been shown to have a causal role in obesity and anorexia [13].

Based on studies in mice, MT-II is a promising compound for reducing appetite, improving insulin sensitivity, and decreasing fat mass [16, 17, 18].

Cognition and Social Bonding

The benefits around cognition and social bonding are again due to the ability of MT-II to bind to melanocortin receptors in the brain [4]. Research in rodents has shown that the expression and activity of melanocortin receptors in the brain declines over time, pointing to a potential use for MT-II in minimizing age-related cognitive decline [19].

Melanotan II peptide therapy also appears to hold promise in the treatment of autism spectrum disorders due to an ability to stimulate the release of oxytocin via binding to the MCR4 receptor. In an autism mouse model, MT-II was able to promote social behavior of mice predisposed to antisocial behavior [20].

(Peptides.org, sponsored) Melanotan II Peptide therapy: benefits, uses, and safety.

Melanotan II Safety and Side Effects

Multiple clinical trials have demonstrated that melanotan II is safe and well-tolerated in healthy male subjects, as well as patients with psychogenic and organic erectile dysfunction [2, 6, 7].

MT-II side effects are considered minor and are typically only experienced for a short period of time following administration, with the frequency and magnitude of symptoms related to dosage. The most common side effects include:

  • Nausea

  • Facial flushing

  • Stomach discomfort

  • Erections

  • Fatigue and yawning

Given the importance of MT-II dosage on the appearance of side effects, researchers should titrate dosage for each study population and are encouraged to reference the section on dosage guidelines included in this article.

As discussed previously, melanogenesis induced by MT-II is hypothesized to decrease the risk of skin cancer [4]. However, publication of a case report of a patient using MT-II who developed melanoma raised concerns about a paradoxical risk of skin cancer from MT-II usage [21].

Study authors noted that the patient also had a history of using tanning beds that predated her MT-II usage and concluded that it was not possible to establish a causal role for MT-II and the development of her case of melanoma.

Since the publication of that case study, no causal link has been established between MT-II and cancer. Another important reference point that will ease researchers’ concerns about any cancer risk is that the related synthetic peptide, afemelanotide, stimulates melanocytes via an identical mechanism and has received FDA approval without any noted cancer risk [11].

Even more doubt was cast on any link between MT-II and cancer, as a recent publication described a cancer suppressing effect of a topical formulation of MT-II that suppressed established melanomas in rodents [22].

Another case report described a 39-year-old male who overdosed on MT-II by injecting 6mg, which is six times the recommended dose, leading to kidney dysfunction and hospital admission [23]. Notably, a qualitative drug screen revealed that the patient also had opiates in his system and the patient confirmed that he had ingested an unidentified “pain-pill” earlier in the day.

In summary, if MT-II is properly dosed, it is a safe and well-tolerated compound that causes only minor symptoms that typically resolve shortly after administration.

Is Melanotan II Legal?

Melanotan II is a synthetic peptide made up of 7 amino acids and like many other research peptides, is legal for purchase, sale, and handling for research purposes only.

MT-II is not available as a medical product as dictated by FDA regulations. As a result, MT-II cannot be marketed in the United States for human consumption or for the treatment of any medical conditions, with similar restrictions applying in Europe.

Given the nascent stage of peptide therapeutics, minimal regulatory framework has been established even within the legal peptide market. This presents a challenging environment for the approval of peptide products to be evaluated in clinical trials and eventually distributed as medical goods.

Despite these challenges, there is tremendous demand for peptide products in the United States and many countries globally, with trends pointing to increasing future demand.

In response to this surge in demand, the FDA has made efforts to establish guidelines for large-scale peptide production [24]. These include rigorous quality control standards around purity requirements, as well as a promise for increased transparency around the clinical pharmacology of peptides. The latter is intended to help facilitate the evaluation of additional peptide therapeutics in clinical trials.

Until these regulatory changes are finalized, researchers are advised to exercise caution and ensure purchasing materials from qualified vendors. Most importantly, as long as MT-II is sourced from a qualified vendor and handled by qualified researchers, MT-II is fully legal.

Melanotan II Dosage and Cycle

The combination of clinical trials using MT-II alongside over two decades of experimental usage of the peptide provides a useful starting point for researchers interested in MT-II.

Clinical trial experience involved the usage of several Melanotan II dosing regimens, depending on whether the research objective was tanning or sexual performance.

In the only study conducted for tanning purposes, authors dosed test subjects with the peptide every other day for two weeks with 0.01mg/kg, increasing the dose by 0.005mg/kg increments if no serious side effects were experienced [2]. For a 175 pound test subject (79.5kg), this translates to a range of doses between 0.8mg and 2.4mg; however it was noted that higher doses resulted in more intense side effects like nausea and fatigue.

Since completion of the trial in 1996, a more conservative dosing regimen is recommended informed by over two decades of use, with a maximum upper limit of 1mg per day. The following sunless tanning protocol incorporates recommendations from experts and suggests starting with a low dose to assess tolerability:

  • Initial dose: To assess tolerance, begin with a dose between 100mcg and 250mcg injected subcutaneously (intranasal guidelines are provided below). Note that there are 1000mcg in 1mg, such that 250mcg is equal to ¼ of a milligram.

  • Subsequent doses: If the initial dose is well tolerated and the desired degree of tanning is not achieved, increase the dose by 250mcg.

For sexual performance purposes, it is recommended that test subjects begin with 250mcg, assess results, and increase dose by 100 to 200mcg if side effects are tolerable and the desired end point has not been achieved. It is not recommended to exceed 1mg per dose.

For intranasal formulations of MT-II, bioavailability will be lower due to reduced absorption through the nasal membrane, compared with injection [25]. Accordingly, a reasonable starting point would be to use the same protocols listed above, but to increase the recommended dosages at each step by up to 50% to compensate for reduced bioavailability.

Importantly, MT-II is often administered prior to UV or sun exposure, as it allows for oxidation of the newly synthesized pigment, producing a more desirable, “golden brown” skin tone.

Once the desired skin tone is achieved, MT-II dosing can be reduced by both reducing the number of injections and by tapering the amount of peptide administered in each injection.

Melanotan II | Injectable vs. Nasal Spray

Since melanotan II was discovered, subcutaneous injection has been the most common way to deliver the peptide, as injection represents the gold standard for maximizing bioavailability and consistency between dosing.

However, nasal sprays represent another viable route for administering peptides and have a long track record of being used in clinical trials and FDA-approved peptide therapies [26]. Accordingly, although MT-II was never evaluated in clinical trials, it is compatible with a nasal spray formulation based on its molecular properties.

While injectable MT-II is typically favored by researchers, the nasal spray format overcomes many of the challenges that researchers may have when including test subjects uncomfortable with injections.

To ensure that the nasal spray is delivered with maximal bioavailability, researchers are advised to observe the following factors and guidelines:

  • Allow for at least one minute between sprays in the same nostril to avoid oversaturation and loss of the peptide suspension due to swallowing.

  • Keep head tilted backwards to avoid loss of the peptide solution from the bottom of the nose.

  • Clear any nasal congestion prior to administration to minimize blockage of the nasal membrane and allow for maximum absorption.

  • Ensure that the spray pump is kept clean and is refrigerated at all times when not in use to minimize contamination and degradation of the peptide.

Overall, the decision of whether to use the injectable or nasal spray format to administer MT-II will depend on the needs of the researcher and test subjects. For study designs in which injections are not prohibitive, injectable MT-II will likely yield better results. However, researchers should not hesitate to try the nasal spray format if injections are problematic for any of the reasons discussed in this section.

Where to Buy Melanotan II Online? | 2024 Edition

Qualified researchers interested in studying the melanotan II peptide may be interested to find out the best place to buy it online.

Our review team at Peptides.org has surveyed several vendors and determined that the best sources for both injectable and nasal spray formats of melanotan II peptide are:

Both vendors were selected based on several important factors, all to ensure researchers’ access to the highest quality peptides:

  • Quality and Purity. Both vendors produce research-grade melanotan II and adhere to rigorous quality control standards, ensuring that test subjects receive pure formulations of peptide.

  • Excellent Pricing. Both of our recommended vendors have competitive pricing without compromising on quality or customer service.

  • Multiple Payment Methods. The vendors accept a variety of payment methods, including major credit cards, Zelle, CashApp, and Venmo.

  • Customer Care. Both have dedicated customer service representatives who can handle any customer questions or concerns.

Researchers interested in starting their research should not hesitate to buy Melanotan II peptides from the vendor.

(Peptides.org, sponsored) Melanotan II Peptide therapy: benefits, uses, and safety.

How to Reconstitute Melanotan II

When using melanotan II, the peptide will arrive as a lyophilized powder in a glass vial. Lyophilization preserves the biological activity of the peptide in a thermally stable matrix that can be safely shipped and kept at room temperature without degrading.

To prepare melanotan II for injection, researchers will first need to reconstitute the peptide with bacteriostatic water, which will dissolve the lyophilized powder into a clear liquid.

To reconstitute melanotan II, ensure that researchers have a sufficient amount of bacteriostatic water available. Bacteriostatic water is recommended to reconstitute melanotan II, as it will protect the peptide against contamination for at least 1 month due to the presence of 0.9% benzyl alcohol.

Once bacteriostatic water is on hand, determine the volume needed to dilute the peptide to the desired concentration, which will be limited by the volume of the vial and refer to these instructions:

  • Clean hands and then swab the rubber stoppers on the top of both the melanotan II vial and the bacteriostatic water container.

  • Insert the needle into the bacteriostatic water container and draw up the required volume of water.

  • Remove the syringe, insert into the melanotan II vial, and completely dispense the bacteriostatic water.

  • Gently rotate the melanotan II vial until the lyophilized powder is completely dissolved.

Once the peptide is reconstituted, keep the vial refrigerated.

Melanotan II FAQ

How to Take Melanotan II

Melanotan II is typically taken prior to sun or UV exposure several times per week until a desired level of tan is achieved, at which point it can be dosed less frequently. For sexual enhancement, MT-II should be administered approximately 1 hour prior to sexual activity.

How is Melanotan II Delivered?

Melanotan II can be delivered via injection or nasal spray, with each format having different advantages and disadvantages.

Is Melanotan II Dangerous?

Melanotan II was found to be safe and tolerable in each of the three clinical trials in which it was evaluated. If administered at the proper dosages, and is uncontaminated, MT-II is considered safe.

Is Melanotan II a Steroid?

No, melanotan II is a peptide, not a steroid and has no affinity for the androgen receptor, nor will it impact endogenous steroid production.

Does Melanotan II Increase Testosterone?

Melanotan II was not shown to have any impact on testosterone during clinical trials. Mechanistically, MT-II would not be expected to increase testosterone, as it binds to melanocortin receptors which do not influence testosterone production.

Does Melanotan II Build Muscle?

Although melanotan II has been shown to improve insulin sensitivity in mice, which could theoretically improve muscle building, it is unlikely that MT-II will have a significant impact on muscle building as it has been found to be an appetite suppressant, which is counterproductive for gaining muscle. MT-II is unlikely to have a significant impact, positive or negative, on muscle building.

Does Melanotan II Cause Weight Gain?

Although never formally studied for its effects on weight gain, melanotan II is unlikely to cause weight gain due to activating melanocortin receptors that reduce appetite and increase fat loss.

Melanotan II Peptide Therapy | Review

Melanotan II is an intriguing compound for researchers interested in the melanocortin system and the physiology of tanning, sexual arousal, metabolism, and cognition.

Although there are other melanotropic compounds that are specific to either tanning or sexual arousal, melanotan II is unique in its ability to be used for both purposes, which may be preferred by some researchers.

Additionally, the availability of both injectable and nasal spray formats of MT-II provides researchers with flexibility around administration.

To source research-grade MT-II, qualified researchers can trust this vendor for injectable MT-II  and for a nasal spray version of the peptide.

References

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  2. Dorr, R. T., Lines, R., Levine, N., Brooks, C., Xiang, L., Hruby, V. J., & Hadley, M. E. (1996). Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life sciences, 58(20), 1777–1784. https://doi.org/10.1016/0024-3205(96)00160-9

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  10. Dhillon, S., & Keam, S. J. (2019). Bremelanotide: First Approval. Drugs, 79(14), 1599–1606. https://doi.org/10.1007/s40265-019-01187-w

  11. Wensink, D., Wagenmakers, M. A. E. M., & Langendonk, J. G. (2021). Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Expert review of clinical pharmacology, 14(2), 151–160. https://doi.org/10.1080/17512433.2021.1879638

  12. Ückert, S., Bannowsky, A., Albrecht, K., & Kuczyk, M. A. (2014). Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies. Expert opinion on investigational drugs, 23(11), 1477–1483. httpsdoi.org/10.1517/13543784.2014.934805

  13. Krashes, M. J., Lowell, B://. B., & Garfield, A. S. (2016). Melanocortin-4 receptor-regulated energy homeostasis. Nature neuroscience, 19(2), 206–219. https://doi.org/10.1038/nn.4202

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  16. Eliason NL, Martin L, Low MJ, Sharpe AL. Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food. Neuropeptides. 2022 Dec;96:102289. doi: 10.1016/j.npep.2022.102289. Epub 2022 Sep 16. PMID: 36155088.

  17. Heijboer, A. C., van den Hoek, A. M., Pijl, H., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Corssmit, E. P. (2005). Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Diabetologia, 48(8), 1621–1626. https://doi.org/10.1007/s00125-005-1838-8

  18. Wikberg, J. E., & Mutulis, F. (2008). Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nature reviews. Drug discovery, 7(4), 307–323. https://doi.org/10.1038/nrd2331

  19. Zhou, Y., Chawla, M. K., Rios-Monterrosa, J. L., Wang, L., Zempare, M. A., Hruby, V. J., Barnes, C. A., & Cai, M. (2021). Aged Brains Express Less Melanocortin Receptors, Which Correlates with Age-Related Decline of Cognitive Functions. Molecules (Basel, Switzerland), 26(20), 6266. https://doi.org/10.3390/molecules26206266

  20. Minakova, E., Lang, J., Medel-Matus, J. S., Gould, G. G., Reynolds, A., Shin, D., Mazarati, A., & Sankar, R. (2019). Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism. PloS one, 14(1), e0210389. https://doi.org/10.1371/journal.pone.0210389

  21. Hjuler, K. F., & Lorentzen, H. F. (2014). Melanoma associated with the use of melanotan-II. Dermatology (Basel, Switzerland), 228(1), 34–36. https://doi.org/10.1159/000356389

  22. Wu, J. C., Tsai, H. E., Hsiao, Y. H., Wu, J. S., Wu, C. S., & Tai, M. H. (2020). Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition. International journal of molecular sciences, 21(2), 681. https://doi.org/10.3390/ijms21020681

  23. Nelson, M. E., Bryant, S. M., & Aks, S. E. (2012). Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clinical toxicology (Philadelphia, Pa.), 50(10), 1169–1173. https://doi.org/10.3109/15563650.2012.740637

  24. ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin (2021).

  25. Costantino, H. R., Illum, L., Brandt, G., Johnson, P. H., & Quay, S. C. (2007). Intranasal delivery: physicochemical and therapeutic aspects. International journal of pharmaceutics, 337(1-2), 1–24. https://doi.org/10.1016/j.ijpharm.2007.03.025

  26. Alabsi, W., Eedara, B. B., Encinas-Basurto, D., Polt, R., & Mansour, H. M. (2022). Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols. Pharmaceutics, 14(9), 1870. https://doi.org/10.3390/pharmaceutics14091870