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Melanotan 2 (MT-2) is a synthetic analogue of alpha-melanocyte-stimulating hormone, created in the 1980s. It has been found to act as a non-selective agonist of melanocortin receptors MC1, MC3, MC4 and MC5.
It has been clinically documented that melanotan II activates MC1 receptor, which leads to melanogenesis, which is why this particular peptide was deemed “barbie drug.”
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Melanotan 2 is a synthetic form of alpha-melanocyte-stimulating hormone (a-MSH), which is naturally found in humans. It first appeared in the 1980s and was developed by scientists working at the University of Arizona after they discovered that a-MSH can cause sexual arousal in rodents, along with darkening of their skin.
Initially created as a way to get a tan without sunbathing, Melanotan 2 is believed to have a diverse range of effects in laboratory settings.
This peptide works by interacting with melanocortin receptors. There are five of them available, each having different functions.
MC-1R: Stimulating this receptor causes darkening of the skin and hair. It is found in melanocytes.
MC-2R: Located in adrenal glands, MC-2R initiates the secretion of cortisol.
MC-3R: It is involved in energy regulation and appetite control.
MC-4R: It causes changes in sexual behavior and feeding. MC-4R may also affect male erectile dysfunction in rodents and energy hemostasis.
MC-5R: This receptor is expressed on pancreatic islet cells and sweat glands.
In laboratory settings involving mice, Melanotan 2 has shown a potential to reverse certain autistic features, mostly concerning ASD or autism spectrum disorder. While there is no treatment available, some research involving oxytocin therapy indicates this compound could mitigate some behavioral problems associated with ASD.
Using the same mice model of maternal immune activation, which can lead to autism, scientists have investigated if MT2 could counteract or reduce ASD behaviors, mostly because MT2 was able to stimulate oxytocin release. In their research, they discovered that the administration of MT-2 reversed impaired communication and decreased social interaction, along with repetitive behaviors linked to autism.
Scientists also found that Melanotan 2 could boost the expression of oxytocin receptors in particular parts of the brain, signaling a direct link between oxytocin and ASD. These findings not only imply potential opportunities for developing treatments for ASD but also preventive measures that could help address issues concerning autism.
Solid evidence suggests that Melanotan 2 can minimize hunger behavior and fat storage in animal models. Researchers have discovered that MC-4R plays a role in food intake and food preferences and that MT-2 is a powerful agonist of MC-4R.
When given to mice, MT-2 caused a significant reduction in food intake and changed their preferences for fatty food. Mice that were given MT-2 ignored fatty foods, which they would have taken otherwise. On the other hand, mice lacking MC-4R receptors consumed fatty foods almost exclusively and were immune to the effect of MT-2.
The studies indicate that the effects of MT-2 are similar to the effects of the hormone leptin. This hormone is also called satiety hormone because it decreases food intake and carvings. However, leptin has never been successful in treating obesity.
A high blood sugar level, increased secretion of glucagon, and production of ketone bodies characterize diabetes. For quite some time, it has been known that leptin prevents these factors by boosting the uptake of glucose, minimizing glucagon production, and obstructing the pathway leading to ketone body formation. It’s important to mention that this doesn’t depend on insulin, while leptin is actively investigated as an alternative solution, which scientists could use to treat diabetes in animal models.
Studies have discovered that leptin’s effects on blood sugar levels are regulated via melanocortin receptors, and that MT-2 generates similar effects.
Considering that Melanotan 2 may affect oxytocin release and behavior in ASD, studies also revealed that MC-4R receptors may play a significant role in impulse control. Previous trials in rats have discovered that MT-2 minimizes alcohol intake while enhancing water intake, even in rodents that prefer alcohol.
These findings demonstrate that MT-2 may not only be successful in treating alcohol-related disorders but also in minimizing desire in the mammalian brain. These studies may open new opportunities for a deeper understanding of not only hunger and alcohol abuse but also the role of oxytocin in impulsive behavior.
ED, or erectile dysfunction, is believed to be a vascular issue, and men often treat it with Viagra and other drugs that enhance blood flow because it reduces vascular resistance. In animal models, scientists discovered that MT-2 could be effective in treating erectile dysfunction. The research also suggests that MT-2 may have a more wide-ranging application than drugs similar to Viagra because of its effect on the central nervous system.
While this peptide showed significant positive effects in animal models, more testing is required before they are used on humans. However, one thing is sure: with how science is developing and research in this field, we hope to experience many positive sides of Melanotan 2.
References:
Minakova E, Lang J, Medel-Matus JS, Gould GG, Reynolds A, Shin D, Mazarati A, Sankar R. Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism. PLoS One. 2019 Jan 10;14(1):e0210389. doi: 10.1371/journal.pone.0210389. PMID: 30629642; PMCID: PMC6328175.
van der Klaauw A, Keogh J, Henning E, Stephenson C, Trowse VM, Fletcher P, Farooqi S. Role of melanocortin signalling in the preference for dietary macronutrients in human beings. Lancet. 2015 Feb 26;385 Suppl 1(Suppl 1):S12. doi: 10.1016/S0140-6736(15)60327-0. PMID: 26312834; PMCID: PMC6548551.
Bjørbaek C, Hollenberg AN. Leptin and melanocortin signaling in the hypothalamus. Vitam Horm. 2002;65:281-311. doi: 10.1016/s0083-6729(02)65068-x. PMID: 12481551.
Guo F, Bakal K, Minokoshi Y, Hollenberg AN. Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo. Endocrinology. 2004 May;145(5):2221-7. doi: 10.1210/en.2003-1312. Epub 2004 Feb 5. PMID: 14764630.
Lee YH, Wang MY, Yu XX, Unger RH. Glucagon is the key factor in the development of diabetes. Diabetologia. 2016 Jul;59(7):1372-1375. doi: 10.1007/s00125-016-3965-9. Epub 2016 Apr 26. PMID: 27115412.
Toda C, Shiuchi T, Lee S, Yamato-Esaki M, Fujino Y, Suzuki A, Okamoto S, Minokoshi Y. Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues. Diabetes. 2009 Dec;58(12):2757-65. doi: 10.2337/db09-0638. Epub 2009 Sep 14. PMID: 19752162; PMCID: PMC2780865.
York DA, Boghossian S, Park-York M. Melanocortin activity in the amygdala influences alcohol intake. Pharmacol Biochem Behav. 2011 Mar;98(1):112-9. doi: 10.1016/j.pbb.2010.12.010. Epub 2010 Dec 15. PMID: 21167196.
Navarro M, Carvajal F, Lerma-Cabrera JM, Cubero I, Picker MJ, Thiele TE. Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice. Alcohol Clin Exp Res. 2015 Aug;39(8):1425-33. doi: 10.1111/acer.12774. Epub 2015 Jun 24. PMID: 26108334; PMCID: PMC4515169.
Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998 Aug;160(2):389-93. PMID: 9679884.
WESSELLS, H. , HRUBY, V. J., HACKETT, J. , HAN, G. , BALSE‐SRINIVASAN, P. and VANDERAH, T. W. (2003), MT‐II Induces Penile Erection via Brain and Spinal Mechanisms. Annals of the New York Academy of Sciences, 994: 90-95
Wessells, H. (1998). Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: Doubleblind placebo controlled crossover study. Nature.com. Available at:
Islam MT, Rumpf F, Tsuno Y, Kodani S, Sakurai T, Matsui A, Maejima T, Mieda M. Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons. Curr Biol. 2022 Sep 26;32(18):3871-3885.e4. doi: 10.1016/j.cub.2022.07.020. Epub 2022 Jul 30. PMID: 35907397.
Lau JKY, Tian M, Shen Y, Lau SF, Fu WY, Fu AKY, Ip NY. Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer's disease transgenic mouse model. Sci Rep. 2021 Feb 23;11(1):4359. doi: 10.1038/s41598-021-83932-4. PMID: 33623128; PMCID: PMC7902646.
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