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Melanotan 2

Melanotan 2

Other names:Melanotan-II, MT II, MT2, Melanotan 2

Polypeptide Melanotan II, also known as MT-2, is a synthetic version of the peptide hormone -melanocyte-stimulating hormone, which is a naturally occurring molecule in your body that is responsible for the creation of skin-darkening pigments known as melanin. It functions by attaching to melanocortin receptors. Melanotan 2 binds to MC-1R to promote skin and hair darkening. It also increases sexual excitement in women and encourages penile erection by tying to the MC-4R.

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What Is Melanotan 2 (MT-2)?

Melanotan 2 (MT-2) is a synthetic derivative of human alpha-melanocyte-stimulating hormone (α-MSH). It was initially developed in the 1980s at the University of Arizona when researchers discovered that α-MSH induced sexual arousal in rodents and caused skin darkening. Originally intended as a sunless tanning option, MT-2 was later found to have a wide range of effects, including:

  • Increasing sexual arousal
  • Promoting tanning or skin pigmentation
  • Reducing compulsive behavior
  • Controlling addiction
  • Suppressing hunger
  • Decreasing glucagon production
  • Reversing certain features associated with autism.

These findings have sparked interest in exploring the potential applications of MT-2 in various areas. [1]

Melanotan 2 Peptide Structure

Melanotan II

Peptide Sequence: Nle-Asp(1)-His-D-Phe-Arg-Trp-Lys(1)
Molecular Formula: C50H69N15O9
Molecular Weight: 1024.198 g/mol
PubChem CID: 92432
CAS Number: 121062-08-6

melanotan2 structure

Authoritative source:PubChem

Melanotan 2 Research

Melanotan 2 and Melanocortin Signaling

Melanotan 2 exerts its effects by binding to specific receptors known as melanocortin receptors. There are five identified melanocortin receptors, each serving different functions. MT-2 primarily binds to MC-4R and MC-1R, with weaker affinity for MC-3R.

  • MC-1R: Found on melanocytes, stimulation of MC-1R leads to skin and hair darkening.
  • MC-2R: Located in the adrenal glands, MC-2R activation promotes the secretion of adrenal hormones, including cortisol.
  • MC-3R: MC-3R is involved in appetite control and energy regulation, although limited knowledge is available regarding this receptor’s functions.
  • MC-4R: Stimulation of MC-4R induces changes in feeding and sexual behavior. It also influences male erectile function and energy homeostasis.
  • MC-5R: MC-5R is expressed in sweat glands and pancreatic islet cells.

Understanding the specific interactions of Melanotan 2 with these receptors provides insights into its diverse physiological effects. [7]

Melanotan 2 and Autism

The latest research on MT-2 has uncovered a significant finding regarding its potential in addressing certain characteristics of autism spectrum disorder (ASD) in a widely used mouse model. Currently, there is no known cure for ASD, but recent studies have suggested that oxytocin therapy might help alleviate some of the behavioral challenges associated with the disorder. In this context, researchers explored the effects of MT-2, which is known to stimulate oxytocin release, on counteracting ASD or reducing common ASD-related behaviors using a mouse model of maternal immune activation known to induce autism.

The study revealed that the administration of MT-2 effectively reversed the reduced communication, impaired social interaction, and repetitive behaviors associated with autism in this particular model. Interestingly, the researchers also observed that MT-2 administration increased the expression of oxytocin receptors in specific regions of the brain. This finding indicates a direct correlation between oxytocin signaling in those areas and the manifestation of ASD-specific behaviors.

These findings offer promising insights into the potential use of MT-2 as a means to address certain aspects of autism and enhance our understanding of the role of oxytocin in ASD-related behaviors. [2]

melanotan2 autism

Impact of MT-2 on sociability in rats with ASD (MIA) showing that MT-2 returns sociability ratings to near the baseline of control animals (C57).

Authoritative source:PubMed

These findings indicate that MT-2 could potentially serve as an effective treatment for alcohol-related disorders, while also shedding light on a fundamental process of craving and desire in the mammalian brain. This research has the potential to provide insights not only into alcohol abuse and hunger, but also into the role of oxytocin in impulsive behavior. Furthermore, it may assist researchers in identifying craving pathways and advancing our comprehension of human motivation across various aspects of life, including work and relationships.

Melanotan 2 and Erectile Dysfunction

Erectile dysfunction (ED) is often attributed to vascular issues and can be effectively treated in the majority of men with medications such as sildenafil (Viagra) that improve blood flow by reducing vascular resistance. However, not all cases of ED are solely caused by vascular issues, making drugs like sildenafil ineffective in a small percentage of men and the majority of women who suffer from hypoactive sexual desire disorder. While it has been known for some time that MT-2 is an effective treatment for ED, research suggests that its actions in the central nervous system give it a broader range of applications compared to drugs like sildenafil. In a study involving men who had not responded to Viagra treatment, eighty percent showed a positive response to MT-2 treatment. MT-2 has been actively investigated as a potential treatment for both male and female sexual desire disorders.[4]

Melanotan 2 Impacts Wakefulness

Our understanding of sleep and arousal is still limited, as the regulation of consciousness is a complex aspect of higher brain function. However, research has revealed that various populations of neurons in the brain play crucial roles in different aspects of arousal, including sleep onset, depth of consciousness, and sleep duration. One specific brain region involved in regulating arousal in response to stress, social interaction, feeding, and other cues is the paraventricular nucleus of the hypothalamus.[5][6]

Studies conducted on mice have shown that stimulation with melanotan 2 can increase arousal by interacting with neuronal fibers in the paraventricular nucleus. Interestingly, this pathway’s stimulation can lead to an immediate transition from both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep to wakefulness. Further research in this field may uncover insights on improving sleep quality and enhancing concentration through modulation of the melanocortin system. This knowledge opens up the possibility of peptides like melanotan 2 being explored as potential nootropics.[7]

Melanotan 2 and Alzheimer’s Disease

Previous studies have demonstrated that the activation of neuropeptides derived from pro-opiomelanocortin (POMC) can rescue synaptic dysfunction caused by neurofibrillary tangles associated with Alzheimer’s Disease. Melanocortin receptors can activate POMC-derived neuropeptides, prompting researchers to investigate the potential utility of melanotan 2 in this context using mouse models. The results of this research indicated that melanotan 2 significantly reduces amyloid accumulation and prominently decreases the presence of the A1 subtype of reactive astrocytes. This is noteworthy because A1 astrocytes are believed to play a key role in neurotoxicity and neuronal death in Alzheimer’s Disease. These findings suggest that activating melanocortin receptors may serve as a potential therapeutic approach for treating Alzheimer’s Disease. Furthermore, this represents a novel avenue for exploring treatments for Alzheimer’s Disease and may also offer a means of mitigating neurotoxicity in other degenerative brain disorders.

MT-2 Research

MT-2 has been extensively studied as a peptide, particularly in relation to human behavior, sexual desire, and impulse control. Clinical trials have been conducted with different forms of the peptide; however, challenges with administration routes have prompted scientists to reassess their approach. Active and ongoing research is being conducted to explore the potential benefits of this specific peptide.

MT-2 has shown to have minimal to moderate side effects and exhibits low oral bioavailability but excellent subcutaneous bioavailability in mice. It is important to note that dosage per kilogram in mice does not directly translate to humans. At Peptide Sciences, the sale of MT-2 is restricted to educational and scientific research purposes only, and it is not intended for human consumption. It is advised to purchase MT-2 only if you are a licensed researcher.

Referenced Citations

[1] E. Minakova et al., “Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism,” PLoS ONE, vol. 14, no. 1, Jan. 2019. 

[2] A. van der Klaauw et al., “Role of melanocortin signaling in the preference for dietary macronutrients in human beings,” Lancet Lond. Engl., vol. 385 Suppl 1, p. S12, Feb. 2015. 

[3] H. Shimizu, K. Inoue, and M. Mori, “The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure,” J. Endocrinol., vol. 193, no. 1, pp. 1–9, Apr. 2007. 

[4] C. Bjørbaek and A. N. Hollenberg, “Leptin and melanocortin signaling in the hypothalamus,” Vitam. Horm., vol. 65, pp. 281–311, 2002. 

[5]  F. Guo, K. Bakal, Y. Minokoshi, and A. N. Hollenberg, “Leptin Signaling Targets the Thyrotropin-Releasing Hormone Gene Promoter in Vivo,” Endocrinology, vol. 145, no. 5, pp. 2221–2227, May 2004. 

[6] Y. H. Lee, M.-Y. Wang, X.-X. Yu, and R. H. Unger, “Glucagon is the key factor in the development of diabetes,” Diabetologia, vol. 59, no. 7, pp. 1372–1375, 2016. 

[7] C. Toda et al., “Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues,” Diabetes, vol. 58, no. 12, pp. 2757–2765, Dec. 2009.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497767/

Referenced Citations

[1] Wessells H, Levine N, Hadley ME, Dorr R, Hruby V.  Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000 Oct;12 Suppl 4:S74-9. doi: 10.1038/sj.ijir.3900582. PMID: 11035391.

[2] Hadley, M. E., & Dorr, R. T. (2006). Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides, 27(4), 921–930.

[3] M. M. Sirufo, L. M. Magnanimi, L. Ginaldi, and M. De Martinis, “Anorexia nervosa and autoimmune comorbidities: A bidirectional route?,” CNS Neurosci. Ther., vol. 28, no. 12, pp. 1921–1929, Sep. 2022, doi: 10.1111/cns.13953.

[4] Li G, Zhang Y, Wilsey JT, Scarpace PJ. Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression. J Endocrinol. 2004 Jul;182(1):123-32. doi: 10.1677/joe.0.1820123. PMID: 15225137.

[5] Olney JJ, Sprow GM, Navarro M, Thiele TE. The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II (MTII), against binge-like ethanol drinking are facilitated by deletion of the MC3 receptor in mice. Neuropeptides. 2014;48(1):47-51. doi:10.1016/j.npep.2013.11.001.

[6] Hjuler, K. F., & Lorentzen, H. F. (2014). Melanoma associated with the use of melanotan-II. Dermatology (Basel, Switzerland), 228(1), 34–36.

[7] J. K. van den Heuvel et al., “Inhibitory Effect of the Melanocortin Receptor Agonist Melanotan-II (MTII) on Feeding Depends on Dietary Fat Content and not Obesity in Rats on Free-Choice Diets,” Front. Behav. Neurosci., vol. 9, p. 358, Dec. 2015, doi: 10.3389/fnbeh.2015.00358.

[8] Zhang Y, Collazo R, Gao Y, Li G, Scarpace PJ. Intermittent MTII application evokes repeated anorexia and robust fat and weight loss. Peptides. 2010;31(4):639-643. doi:10.1016/j.peptides.2009.12.019.

[9] Han D, Wang Y, Chen J, Zhang J, Yu P, Zhang R, Li S, Tao B, Wang Y, Qiu Y, Xu M, Gao E, Cao F. Activation of melatonin receptor 2 but not melatonin receptor 1 mediates melatonin-conferred cardioprotection against myocardial ischemia/reperfusion injury. J Pineal Res. 2019 Aug;67(1):e12571. doi: 10.1111/jpi.12571. Epub 2019 Apr 12. PMID: 30903623.

[10] Wang W, Guo DY, Lin YJ, Tao YX. Melanocortin Regulation of Inflammation. Front Endocrinol (Lausanne). 2019;10:683. Published 2019 Oct 9. doi:10.3389/fendo.2019.00683.

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

[12]Krashes, M. J., Lowell, B://. B., & Garfield, A. S. (2016). Melanocortin-4 receptor-regulated energy homeostasis. Nature neuroscience, 19(2), 206–219.

Author of this article:

Dr. Jean Zeng graduated from king’s college london Faculty of Life Sciences & Medicine.

Scientific Journal paper Author:
  1. Mariël P Ter Laak 

Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands

  1. Joakim Riikonen

Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland

  1. Ryouichi Banno

Department of Metabolic Diseases, Field of Internal Medicine, Nagoya University Graduate School of Medicine

  1. Hiroshi Arima

Department of Metabolic Diseases, Field of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

Institute of Pharmacology, Russian Academy of Medical Sciences, 8 Baltiyskaya Street, 125315 Moscow, Russia

In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. peptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide.

Author of this article:

Dr. Jean Zeng graduated from king's college london Faculty of Life Sciences & Medicine.

Scientific Journal paper Author:

Stephen C. Bain
Diabetes Research Group, Swansea University Medical School, Swansea, SA2 8PP, UK
Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, SA2 8QA, UK

In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. Polypeptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide.