Melanotan 2 Peptide overview and research applications

Melanocortins are a class of tiny protein hormones produced when the proopiomelanocortin (POMC) gene is cut during translation. The recognized melanocortin hormones are alpha-, beta-, and gamma-melanocyte-stimulating.

Adrenocorticotropic hormone is another name for this group of hormones. Among the five known melanocortin receptors (MC1R–MC5R), most exhibit tissue-specific expression patterns and variable binding affinities for the various melanocortin hormones.

Alpha-MSH, AGRP, MC3R, and MC4R comprise the central melanocortin system. It is thought that AGRP acts as an MC3R antagonist, whereas alpha-MSH acts as an MC4R agonist. Researchers believe this central melanocortin system may be crucial for regulating food intake and overall body mass index.

Pigmentation, lipolysis, thermogenesis, sexual behavior, memory, and inflammatory response are just a few of the complex processes in which melanocortins have been implicated via genetic research and knock-out mouse models.

Melanocortins and their receptors have recently been the focus of pharmacological interventions in the context of physiological functions. MCIR has anti-inflammatory potential, and MC2R is believed to hold potential in the context of glucocorticoid deficit.

Studies suggest MC3R and MC4R may be probable targets for weight management. Although MC5R's exact function is unknown, the available data indicate an exocrine gland function.

Melanotan II Peptide: What is it?

Studies suggest that Afamelanotide, or Melanotan I, has a shorter half-life than Melanotan II, a synthetic cyclic lactam analog of naturally occurring α-MSH (Melanocyte-stimulating hormone). Melanotan I [Nle4, D-Phe7] α-MSH is hypothesized to be an effective, non-selective version of α-MSH that binds to and may activate the MC1R, MC3R, MC4R, and MC5R receptors.

Research suggests it might have high biodistribution and stability in living organisms, although it has limited permeability to the blood-brain barrier.

The cyclic structure of Melanotan II (MTII), also known as Ac-Nle-c[Asp5, DPhe7, Lys10] α -MSH-NH2, gives it improved stability (T1/2: 1-2 h) and blood-brain barrier permeability, researchers suggest. Investigations purport that, at the same time, it may be just as potent and has the same spectrum of effects as MTI.

Reportedly, Melanotan II may engage signaling pathways more comparably analogized to endogenous melanocortins. Findings imply the melanocortin receptors MC1R, MC3R, MC4R, and MC5R may be non-selectively agonistically activated by Melanotan II.

Peripheral MC1R binding is the primary mechanism by which Melanotan II is believed to induce melanogenesis. Crucial to MC4R and MC3R are their impacts on metabolism and arousal.

Melanotan II Peptide and Sexual Dysfunction

The regulation of sexual function, including the stimulation of lordosis in female rats and erectile activity in male rats, is also connected to central melanocortin receptors. There is a correlation between lordosis and MC3R, and erectile function and peripheral and central MC4R are also linked.

There have been clinical studies looking at melanocortins as potential adjuvants for erectile dysfunction and female sexual dysfunction.

It seems that the first "true" aphrodisiac, bremelanotide (PT-141, another melanocortin MC4R specific), was given to female rats and appeared to increase their soliciting behavior in laboratory trials considerably.

Animal studies have suggested that it may stimulate sexually aroused behaviors in female rats before copulatory activity, and early clinical results also point to a potential function in enhancing sexual desire and arousal in female models.

In addition to their potential for sexuality via reward-based neuropharmacology, melanocortin peptides have been speculated to influence dopaminergic neurotransmission.

Melanotan II Peptide and Immunity

At first, the host immune system's reaction to an infection involves inflammation and proinflammatory mediators. Nevertheless, inflammatory bowel illnesses (such as ulcerative colitis, irritable bowel syndrome, and Crohn's) are among several inflammatory diseases in which persistent, uncontrolled inflammation plays a harmful role.

The importance of MC1R, MC3R, MC4R, and MC5R in alleviating chronic inflammation has been suggested in studies.

Melanocortin receptors are expressed by inflammatory cells, monocytes/macrophages, neutrophils, and cells derived from tissues, such as mast cells. Lymphocytes express MC1R, MC3R, and MC5R in addition to monocytes/macrophages and microglia.

Lymphocytes' proinflammatory effects may have shifted to inhibitory ones due to signaling via these receptors, which may impact antigen-presenting cells like monocytes and macrophages.

Multiple in vitro studies have purported that signaling via the melanocortin receptor may result in immunomodulatory and anti-inflammatory effects.

In the presence of a proinflammatory stimulus and mediating molecules like IL-1β, α-MSH has been speculated to decrease the production or secretion of the proinflammatory cytokines interferon-γ, TNF-α, IL-1, IL-6, IL-8, and growth-regulated oncogene-α (Gro-α) in vitro.

Uveitis, dry eye, rheumatoid arthritis, inflammatory bowel illnesses (IBD, Crohn's, ulcerative colitis), nephritis, and dermatologic indications are among the inflammatory diseases in which MC1r is hypothesized to be elevated.

Research suggests the MC1r peptides may control the immune system and resolve proinflammatory responses; they may also have an anti-inflammatory impact.

In progressive neuroinflammatory illnesses like multiple sclerosis (MS), MC1R agonists might have the potential to restore the integrity of the blood-brain-barrier (BBB), which in turn may improve Treg activity and prevent immune cell infiltration into the central nervous system (CNS).

Visit Core Peptides for more educational articles and high-quality research peptides.

References

[i] Cai M, Mayorov AV, Ying J, et al. Design of novel melanotropin agonists and antagonists with high potency and selectivity for human melanocortin receptors. Peptides. 2005;26:1481–1485.

[ii] Kim ES, Garnock-Jones KP. Afamelanotide: A review in erythropoietic protoporphyria. Am J Clin Dermatol. 2016;17(2):175-85.

[iii] Langendock JG, Balwani M, Anderson KE, et al. Afamelanotide for Erythropoietic Protoporphyria. N Eng J Med. 2015;373(1):48-59.

[iv] Adan RAH, Tisesjema B, Hillebrand JJG, et al. The MC4 receptor and control of appetite. Br J Pharmacol. 2006;149(7):815-27.

[vi Wessells H, Levine N, Hadley ME, et al. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12 (Suppl 4):S74-9.

[vii King SH, Mayorov AV, Balse-Srinivasan P, et al. Melanocortin receptors, nootropic peptides and penile erection. Curr Top Med Chem. 2007;7(11):1098-1106.

[vii] Ven der Ploeg LHT, Martin WJ, Howard AD, et al. A role for the melanocortin 4 receptor in sexual function. PNAS.2002;99(17):11381-11386.

#FeatureByAttiqButt