Description of Melatonan 2

A synthetically produced peptide Melatonan 2, a variant of Melatonan 1, mimics non-selectively the action of melanocortin peptides by binding their receptors, which are involved in various functions in human body as pigmentation, immune response or even in sexual functions. Melatonan 2 was researched in many fields of therapeutic use as controlling addiction behavior, hunger or reversing features of autism. It also stimulates production of melatonin and eumelanin responsible for skin or hair pigmentation and tanning. Now, let us demonstrate particular results of various studies, which has revealed mechanisms how this peptide can work.

Research Confirmed Effects

1. Melatonan 2 and Melanocortin Receptors

Melatonan 2 operates through the activation of certain melanocortin receptors, specifically MC-1R receptors responsible for signaling the production of melanin, and so darkening the skin and hair color. Additionally, studies report that MT2 binds also MC-4R receptors and thus improves glucose and cholesterol metabolism or sexual behavior, and induces enhanced thermogenic and anorexic responses. It also slightly binds to MC-3R receptors responsible mostly for appetite control and energy regulation. The melanocortin system, a network of hormonal and neuropeptidergic pathways, plays a crucial role in various physiological processes.

2. Melatonan 2 and Its Impacts in Autism

Melanotan 2, a melanocortin receptor 4 (MC-4R) agonist, has shown potential to reverse certain autistic features in a mouse model of autism spectrum disorder (ASD). In a study involving a maternal immune activation (MIA) model, adult male mice with autism-like features were treated with Melanotan 2 over seven days. The results demonstrated that MT2 administration improved social behavioral metrics, which had been impaired in the MIA mice. These mice typically exhibit decreased social interaction, diminished vocal communication, and increased repetitive behaviors—common traits of ASD. Following treatment with Melanotan 2, these autism-like behaviors were notably reduced, suggesting a therapeutic role for the peptide in modulating oxytocin-related pathways.

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3. Melatonan 2 and Hunger

Melanotonan 2 can evidently reduce fat and hunger behavior in animal models, as it was found that MC-4R receptor plays important role in food intake. Research into the role of melanocortin signaling in human dietary preferences has revealed that mutations in MC-4R can affect the intake and preference for fats and sugars. A study that compared 24 obese patients with MC-4R deficiency to 80 healthy controls (40 obese and 40 lean) found that those with MC-4R mutations consumed significantly more high-fat meals. In an ad-libitum meal experiment with varying fat content, patients with MC-4R mutations consumed 95% more of the high-fat meal compared to lean controls, and 65% more compared to obese controls. This indicates that the melanocortin pathway plays a significant role in fat preference.

Further research into the leptin-melanocortin system has illuminated its critical role in human weight regulation and the pathogenesis of obesity. Genetic mutations leading to obesity in both humans and murine models reveal that defects in the leptin-melanocortin pathway can cause severe obesity as a dominant phenotypic feature. Conditions such as leptin deficiency, leptin receptor deficiency, proopiomelanocortin (POMC) deficiency, and MC-4R deficiency can lead to substantial weight gain.

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4. Melatonan 2 and Diabetes

Glucagon, a hormone involved in glucose homeostasis, has a key role in the development of diabetes. Research indicates that glucagon excess, rather than insulin deficiency, is crucial for diabetes pathogenesis. Hyperglucagonaemia, or high glucagon levels, is a common feature in all forms of diabetes. Glucagon stimulates hepatic glucose production, leading to hyperglycemia. Glucagon receptor null mice do not develop diabetes even with beta cell destruction, indicating that glucagon receptor activation is necessary for diabetes development. Studies also show that insulin alone cannot effectively manage diabetes because it doesn't address glucagon's catabolic effects, whereas treatments targeting glucagon suppression, such as leptin or glucagon receptor antibodies, could lead to better glucose regulation.

Leptin and melanocortin receptors (MCRs) have been linked to glucose regulation in peripheral tissues through the medial hypothalamus. Research suggests that the ventromedial hypothalamus (VMH) plays a central role in leptin-induced glucose uptake in skeletal muscle, brown adipose tissue (BAT), and heart tissue. Injection of the melanocortin receptor agonist Melanotan 2 (MT2) into the VMH also increased glucose uptake in these tissues, indicating that both leptin and MT2 operate through MCRs to modulate glucose metabolism. However, the arcuate nucleus (ARC) of the hypothalamus showed increased glucose uptake only in BAT after leptin injection, while other nuclei like the dorsomedial hypothalamus (DMH) or the paraventricular hypothalamus (PVH) had no effect on glucose uptake when injected with leptin or Melatonan 2. These findings demonstrate that different regions of the hypothalamus have distinct roles in mediating glucose uptake, which can inform future therapeutic strategies for managing diabetes through targeted modulation of specific hypothalamic nuclei.

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5. Melatonan 2 and Reduced Alcohol Intake

Melanotan 2 (MT-2), known for its effects on the melanocortin-4 receptor (MC-4R), has been found to play a role in reducing alcohol intake. Studies involving rats demonstrated that MT-2 reduced alcohol consumption while increasing water intake, indicating its potential impact on impulse control and preference for beverages. Interestingly, an antagonist of MC-4R had an opposite effect, suggesting that MC-4R activation by MT-2 influences preference for alcohol. The amygdala, a brain region involved in emotion and behavior regulation, appears to be the site of this action, highlighting the complexity of neural pathways involved in regulating alcohol consumption.

Further studies showed that combining MT-2 with naltrexone, a commonly used drug for treating alcohol abuse, can increase the effectiveness of naltrexone in reducing binge-like alcohol drinking. This synergistic effect, with MT-2 boosting naltrexone's efficacy more than seven-fold, suggests a promising avenue for treating alcohol-related disorders. The findings point towards a broader role of MC-4R in impulse control and behavioral regulation, hinting at new approaches for understanding and treating impulsivity, cravings, and possibly even other forms of addictive behavior. These insights into MT-2 and MC-4R could eventually lead to novel therapeutic strategies not only for alcohol abuse but also for other disorders involving impaired impulse control and craving.

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6. Melatonan 2 and Erectile Dysfunction

Melanotan 2 has demonstrated effectiveness in treating psychogenic erectile dysfunction in men. In a double-blind, placebo-controlled crossover study involving men with erectile dysfunction (ED) of non-organic origin, MT2 induced clinically apparent erections in 8 out of 10 participants, with a mean duration of tip rigidity greater than 80% lasting 38 minutes, compared to only 3 minutes with a placebo. The study showed that MT2 is a potent initiator of erections in men with psychogenic ED, with manageable side effects such as nausea, stretching, yawning, and decreased appetite. These results suggest that Melatonan 2 may be a viable treatment option for individuals with psychogenic ED and could have broader applications in addressing sexual desire disorders, expanding the scope of ED treatment beyond traditional medications like sildenafil (Viagra). Further research into the mechanism of action for MT-II revealed that the peptide induces penile erection through both brain and spinal pathways, mediated by melanocortin receptors

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References

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13. M. T. Islam et al., “Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons,” Curr. Biol. CB, pp. S0960-9822(22)01121–6, Jul. 2022, doi: 10.1016/j.cub.2022.07.020.
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