Melanotan 2 Peptide
Melanotan 2 peptide is a synthetic analog developed to mimic the mechanism of action of alpha-MSH. Melanocyte-stimulating hormone 2 (MSH-2) is similar to MSH-1 in potency, range of receptors, and effect, but possesses greater in vivo stability, blood-brain permeability, and longer half-life.
The melanocortin system consists of melanocyte-stimulating hormone (MSH), ACTH, five G-protein coupled receptors (MR1R-MR5R), and endogenous antagonists (Agouti & Agouti-related proteins). The central melanocortin system consists of alpha-MSH, agouti-related proteins, and MC3R and MC4R. Studies have established the roles of these melanocortins in various complex biological pathways.
Melanin is a compound that imparts pigment to the skin, hair, and eyes. It is produced by skin cells called melanocytes in cell structures called melanosomes. It has a pivotal role in photoprotection and prevents the development of melanoma.
The mechanism involves a signaling cascade by activation of MC1R. Research studies in the synthetic Melanotan peptides suggest MC1R is activated by binding of Melanotan 1 or 2. This activates adenylate cyclase AC leading to cAMP stimulation. cAMP causes phosphorylation of cAMP response-element-binding CREB by activating protein kinase A PKA. This phosphorylated CREB, after binding to CRE on the microphthalmia-associated transcription factor MTIF gene, causes the production of MTIF protein. All this leads to an increased quantity of melanogenic enzymes in melanocytes. MC1R polymorphism is responsible for the ethnic variability in skin color in response relative to ultraviolet radiation exposure.
2. Sexual and Erectile Dysfunction
Melanocortin peptides have been studied for their potential effects in erectile functioning and female sexual dysfunctions. Studies have suggested a significant role of MC3R in peripheral and central receptors. In some studies, Bremelanotide (PT-141) administration – acting on MC4R – has profound aphrodisiac potential in female rats, promoting pre-copulatory behavior.
Some preliminary clinical studies have also been shown to enhance sexual drive in women. Studies have also suggested the role of melanocortin peptides in sexuality through dopaminergic transmission.
3. Immunity Research
Inflammation is a natural host protective phenomenon, but unchecked and prolonged inflammation can deteriorate the host immune system. We see this in chronic inflammatory diseases such as inflammatory bowel disease. A study has shown the potential of receptors MC1R, MC3R, MC4R, and MC5R in regulating host inflammatory response.
The inflammatory cells express melanocortin receptors. Monocytes, macrophages, lymphocytes, and microglia possess MC1R, MC3R, and MC5R. By modulating these receptors, scientists can downregulate inflammatory pathways even in the presence of proinflammatory mediators such as cytokine interferon-gamma, TNF-alpha, IL-1, IL-6, IL-8, and growth-regulated oncogene-alpha.
Naturally occurring Alpha-MSH plays its anti-inflammatory role in several ways, such as:
- Downregulating IL-8 receptors and non-cytokine mediators, e.g., NO2 and iNOS.
- Reduction in migration of inflammatory cells and cell-adhesion molecule expression.
- Enhancing the activity of anti-inflammatory cytokine IL-10.
- Inhibition of NF_kB proinflammatory pathway.
- Reduction in chemotaxis of neutrophils by inhibiting superoxide radical production.
MC1R plays a significant role in various chronic inflammatory diseases by regulating the immune system to combat proinflammatory mediators. MC1R agonists improve blood-brain barrier efficiency and prevent penetration of inflammatory cells into the CNS. This is of great value in neuroinflammatory diseases such as multiple sclerosis.
Another mechanism by which melanocortin receptors (mainly MC3R and MC4R) express anti-inflammatory effects is a cholinergic anti-inflammatory pathway through the vagus nerve and alpha-7 receptors. This plays its role in ischemic brain and heart conditions and autoimmune regulation.
Melanotan 2 peptide has been suggested to enhance body metabolism via MC4R binding and researchers hypothesize that it can potentially improve cholesterol and glucose metabolism. MC4R activated by alpha-MSH comprises the brain melanocortin system’s efferent limb and maintains body weight homeostasis.
The pharmacological antagonists of MC4R led to weight gain, while the agonist led to the contrary in laboratory experiments. It was reported that chronic activation of MC4R leads to persistent high BP despite weight loss, and this BP can be controlled by adrenoceptor blockade.
Melanin is present in excess in the adipose tissue of obese individuals owing to its anti-inflammatory and anti-oxidative properties. The body of these individuals is under oxidative stress.
6. Brain Inflammation
The melanocortin receptors help resolve inflammation in brain tissue by modulating NF-kappaB-mediated transcription following brain injury. Naturally occurring Alpha-MSH has also been demonstrated to hold neuroprotective properties. The melanocortins accelerate neuro-physical recovery after spinal cord injury and repair. MC1R and MC4R modulation may have many beneficial effects in treating Alzheimer’s, depression, autism spectrum disorder, and schizophrenia.
7. Alcohol and Drug Abuse
Many research studies have suggested the potential of Melanotan 2 peptide for supporting opioid and alcohol addiction treatments. The melanocortin system promotes tolerance to the antinociceptive property of morphine through MC4R. MC4R and opioid receptors’ distribution significantly overlap in various brain and spinal cord areas, thus providing the neuroanatomical basis for this effect.
There are laboratory study reports supporting the theory that Melanotan 2 peptide may enhance the impact of naltrexone to blunt ethanol intake. The melanocortin system also plays its part by regulating mesostriatal and mesolimbic dopamine systems in the reward-based addiction phenomenon.
8. Role in Cardiovascular System
Alpha and gamma-MSH raise heart rate and blood pressure through sympathetic system stimulation by activating alpha-MSH by MC4R and gamma-MSH by sodium channels in CNS.
Studies have suggested the role of melanocortin peptides in resolving inflammation and preventing reperfusion injury following ischemia through MC3R in association with the cholinergic anti-inflammatory pathway.
The peptide available for sale is strictly for research and laboratory use, and is unapproved for human consumption or personal use.
NOTE: The information found in this article is intended for educational or informational purposes only. Some or all of the content in these articles is not substantiated by a medical professional and may be based on the writer’s opinions, who may not be a medical or accredited professional. Not intended for personal use. Please review our Terms and Conditions.
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.