Melanotan-2 Peptides: Consequences for Future Study

Melanotan-2 Peptides: Consequences for Future Study

Synthetic Melanotan 2 peptide is an analog of natural -MSH. Research suggests the impact, receptor specificity, and possible action of MSH 2 may be identical to those of MSH 1. It may more readily cross the blood-brain barrier, and may have a prolonged half-life, as suggested by clinical trials.

Studies suggest that melanocyte-stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), five G-protein coupled receptors (MR1R-MR5R), and natural inhibitors may make up the melanocortin system (Agouti & Agouti-related proteins). Alpha-MSH, agouti-related proteins, MC3R, and MC4R comprise the central melanocortin system. The functions of these melanocortins in numerous intricate biochemical processes have been suggested through research.

Melanotan-2 Research Studies

Melanotan-2 And Pigment

Melanin gives the skin, hair, and eyes natural colors. Melanocytes, which are epidermis cells, generate it in organelles called melanosomes. Research suggests that, in this case, MC1R stimulation may trigger a signaling chain.

Studies suggest Melanotan 1 or 2 may bind to MC1R and initiate its activity. This process stimulates cAMP production by activating adenylate cyclase AC [i]. Protein kinase A (PKA) is activated in reaction to cAMP, which phosphorylates cAMP response element-binding CREB.

After attaching to CRE on the MTIF gene, which is linked with microphthalmia, this modified CREB triggers the creation of the MTIF protein. As a result, more melanogenic enzymes are produced by melanocytes. Research speculates that polymorphisms in the MC1R gene may cause ethnic differences in the skin’s reaction to UV rays.

Melanotan-2 And Impotence

Researchers have looked into potentially using melanocortins for genital problems in both sexes. The MC3R has been suggested in studies to play an important part in peripheral and central receptors. Bremelanotide (PT-141), an aphrodisiac that may stimulate pre-copulatory activity in female rodents, has been speculated to have a significant aphrodisiac impact in some experiments.

Melanotan-2 has been suggested in some early clinical trials to increase arousal in test subjects potentially. [ii] It has also been speculated that melanocortin peptides may play a part in libido via dopaminergic signaling.

Melanotan-2 and Defense

Although inflammation initially serves to defend the host, it can weaken the immune system if allowed to persist for too long. This aspect is evident in IBD and other persistent inflammatory conditions. One research suggested that MC1R, MC3R, MC4R, and MC5R may be crucial in controlling the host’s inflammation reaction

Research implies that melanocortin receptors may be highly represented among the inflammation cells. The MC1R, MC3R, and MC5R are found on monocytes, macrophages, lymphocytes, and microglia. By adjusting the levels of these receptors, researchers might suppress inflammatory pathways [iii] despite proinflammatory molecules like interferon-gamma, tumor necrosis factor-alpha, interleukin-1, interleukin-6, interleukin-8, and growth-regulated oncogene alpha.

Studies suggest that multiple mechanisms may allow alpha-MSH to exert its anti-inflammatory effects:

  • Potentially inhibiting the production of IL-8 receptors and other non-cytokine molecules like NO2 and iNOS.
  • Potentially reducing the production of cell-adhesion molecules and decreasing the movement of inflamed cells.
  • Potentially increasing IL-10’s effectiveness as an anti-inflammatory mediator.
  • Potentially stopping the pathogenic NF-kB pathway.
  • Potentially decreasing neutrophil chemotaxis because superoxide radical generation is blocked.

Further research speculates that MC1R may significantly impact the immune system by possibly eliminating inflammation molecules. Agonists for the MC1R may increase the efficacy of the blood-brain barrier and block the insertion of inflammatory cells into the central nervous system. In neuroinflammatory conditions like multiple sclerosis, this may be of tremendous help.

Additional studies suggest that the vagus nerve and alpha-7 receptors are part of an acetylcholine anti-inflammatory system through which melanocortin receptors (primarily MC3R and MC4R) may exert their anti-inflammatory actions. This aspect is important in preventing brain and cardiac attacks and controlling the defense system.

Melanotan-2 and Metabolism

Clinical trials suggest Melanotan 2 peptide may mediate improved lipid and glucose metabolism via MC4R binding. The efferent branch of the brain melanocortin system, comprised of MC4R triggered by alpha-MSH, possibly regulating energy balance and body weight. [iv]

In one study, MC4R inhibitors may have caused weight increases, while the agonist had the opposite action. Adrenoceptor inhibition may possibly mitigate hypertension caused by prolonged MC4R activation, which occurs despite a reduction in body weight.

Melanotan-2 Peptide and Brain Inflammation

Researchers speculate that melanocortin receptors may aid in inflammatory resolution by regulating NF-kappaB-mediated transcription after brain damage. Studies suggest brain cells might be protected by alpha-MSH. The melanocortins may hasten neuro-physical healing following spinal cord damage and surgery, as research speculates. [v]

Melanotan-2 And Substance Addiction 

Numerous studies have suggested Melanotan 2 peptide’s potential involvement in opiate and alcohol dependency. Research speculates that the melanocortin system’s MC4R may facilitate tolerance to the analgesic effects of morphine. The neuroanatomical foundation for this impact is found in the similar distribution of MC4R and opioid receptors in several brain and spinal cord regions. [vi]

Research findings suggest that Melanotan 2 peptide may boost naltrexone’s ability to reduce alcohol consumption when tested in a laboratory setting. Studies suggest that the melanocortin system may allegedly participate in reward-based addiction by controlling the mesostriatal and mesolimbic dopamine networks.

Melanotan-2 and The Coronary System

Research suggests that alpha-MSH (via MC4R) and gamma-MSH (via sodium channels in the central nervous system) may increase heart rate and blood pressure by stimulating the autonomic nervous system.

It has been hypothesized that melanocortin peptides, via MC3R and the acetylcholine anti-inflammatory pathway, may help to reduce inflammation and protect against reperfusion damage after ischemia.

Only academic an d scientific institutions are permitted to use Melanotan -2. If you are a researcher interested in purchasing Melanotan peptides for your clinical studies, you can do so by visiting Biotech Peptides. Please note that none of the items listed are approved for human or animal consumption. Laboratory research chemicals are only for in-vitro and in-lab use. Any kind of physical introduction is illegal. Only authorized academics and working professionals may make purchases. The content of this article is intended only for instructional purposes.


[i] McMillan TR, Forster MAM, Short LI, Rudecki AP, Cline DL, Gray SL. Melanotan II, a melanocortin agonist, partially rescues the impaired thermogenic capacity of pituitary adenylate cyclase-activating polypeptide deficient mice. Exp Physiol. 2021 Feb;106(2):427-437. doi: 10.1113/EP088838. Epub 2020 Dec 17. PMID: 33332767.

[ii] Giuliano F, Clément P, Droupy S, Alexandre L, Bernabé J. Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience. 2006;138(1):293-301. doi: 10.1016/j.neuroscience.2005.11.008. Epub 2005 Dec 19. PMID: 16360286.v

[iii] Getting SJ, Di Filippo C, Christian HC, Lam CW, Rossi F, D’Amico M, Perretti M. MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct. J Leukoc Biol. 2004 Oct;76(4):845-53. doi: 10.119/jlb.0306175. Epub 2004 Jul 26. PMID: 15277567.

[iv] do Carmo JM, da Silva AA, Rushing JS, Pace B, Hall JE. Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons. Am J Physiol Regul Integr Comp Physiol. 2013 Aug 15;305(4):R359-68. doi: 10.1152/ajpregu.00518.2012. Epub 2013 Jul 10. PMID: 23842677; PMCID: PMC3833394.

[v] Muceniece R, Zvejniece L, Liepinsh E, Kirjanova O, Baumane L, Petrovska R, Mutulis F, Mutule I, Kalvinsh I, Wikberg JE, Dambrova M. The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model. Peptides. 2006 Jun;27(6):1443-50. doi: 10.1016/j.peptides.2005.12.002. Epub 2006 Jan 18. PMID: 16414147.

[vi] Navarro M, Cubero I, Knapp DJ, Thiele TE. MTII-induced reduction of voluntary ethanol drinking is blocked by pretreatment with AgRP-(83-132). Neuropeptides. 2003 Dec;37(6):338-44. doi: 10.1016/j.npep.2003.10.003. PMID: 14698676.