Melanotan II
Also known as: MT-II, MT-2, Melanotan 2
Melanotan II is a synthetic analog of alpha-melanocyte stimulating hormone. It was developed for research into tanning, sexual function, and appetite regulation.
Melanotan II Overview & Molecular Profile
Melanotan II is a cyclic lactam analog of alpha-melanocyte stimulating hormone (α-MSH). Originally developed at the University of Arizona, it has been studied for its effects on skin pigmentation, sexual function, and appetite. The peptide acts on various melanocortin receptors, producing multiple biological effects.
Mechanism of Action: Receptor Agonism & Metabolic Pathways
Melanotan II is a non-selective melanocortin receptor agonist, affecting MC1R (pigmentation), MC3R, MC4R (sexual function, appetite), and MC5R. By activating MC1R on melanocytes, it stimulates melanin production. Its effects on MC3R and MC4R influence sexual behavior and appetite regulation.
Research-Observed Effects
Melanogenesis
Research demonstrates Melanotan II's potent melanogenic effects through direct activation of melanocortin-1 receptors (MC1R) on melanocytes, triggering increased tyrosinase activity and eumelanin production that results in progressive skin darkening. Clinical studies have documented significant increases in melanin index scores within 2-4 weeks of administration, with enhanced tanning response to UV exposure and photoprotection research applications. The peptide induces melanin synthesis through cyclic AMP pathway activation, phosphorylation of CREB transcription factors, and upregulation of melanogenesis-related genes including MITF and TYR. Research has shown that Melanotan II can produce visible skin pigmentation changes even without sun exposure, though UV radiation synergistically enhances the tanning effect and provides more natural appearance outcomes. These melanogenesis promotion properties have significant implications for skin pigmentation research, photoprotection mechanism studies, and understanding the molecular basis of melanin production for potential vitiligo treatment applications and sun damage prevention investigations.
Sexual Function Effects
Extensive research demonstrates Melanotan II's pronounced pro-sexual effects through activation of melanocortin-3 and melanocortin-4 receptors (MC3R/MC4R) in hypothalamic nuclei controlling sexual behavior and arousal. Clinical studies in both men and women have documented increased spontaneous erections, enhanced libido, and improved sexual satisfaction scores following subcutaneous administration of the peptide. The sexual enhancement effects occur through central nervous system mechanisms independent of peripheral vascular changes, involving activation of oxytocinergic pathways and modulation of dopamine signaling in reward-related brain circuits. Research has shown onset of sexual function effects within 1-3 hours of administration, with duration of action extending up to 72 hours in some study subjects, making it distinct from fast-acting vasodilator treatments. These findings have positioned Melanotan II as an important research compound for investigating central regulation of sexual function, libido enhancement mechanisms, and the neurobiological connections between melanocortin signaling and sexual motivation pathways.
Appetite Modulation
Research indicates Melanotan II produces significant appetite-suppressing effects through activation of melanocortin-4 receptors (MC4R) located in the paraventricular nucleus and other hypothalamic regions controlling food intake and energy balance. Animal studies have demonstrated reduced food consumption, decreased body weight gain, and altered feeding behaviors following chronic Melanotan II administration, with effects mediated through the central melanocortin-leptin signaling axis. The peptide's anorectic properties appear to involve modulation of neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons that normally stimulate appetite, creating a shift toward reduced hunger signals. Clinical observations have noted decreased appetite and potential weight management effects in human subjects receiving Melanotan II for other research purposes. These appetite regulation effects have generated interest in melanocortin pathway research for obesity treatment development, eating disorder mechanisms, and understanding the complex neuroendocrine control of energy homeostasis and metabolic health improvement.
Fat Metabolism Effects
Emerging research suggests Melanotan II may influence fat metabolism through melanocortin receptor activation in both central and peripheral tissues, with studies documenting effects on lipolysis and adipocyte function. Animal research has shown MC4R activation increases sympathetic nervous system activity to adipose tissue, promoting fatty acid release and oxidation through enhanced beta-adrenergic signaling pathways. Studies indicate the peptide may preferentially affect visceral fat stores, which have higher melanocortin receptor expression than subcutaneous adipose depots, suggesting potential applications in abdominal fat reduction research. Research has documented increased energy expenditure and thermogenesis in treated animals, contributing to negative energy balance independent of appetite suppression effects. These fat metabolism optimization properties position Melanotan II as a research tool for investigating melanocortin-mediated metabolic regulation, body composition modification mechanisms, and the development of novel approaches to obesity and metabolic syndrome research.
Research Dosing Information
Research studies have used varying dosages, typically in the range of 0.25-1 mg. Administration is subcutaneous in research protocols.
Note: Dosing information is provided for research reference only and is based on published studies using research subjects. This is not a recommendation for any use.
Research Studies & References
Clinical studies of melanocortin agonists for tanning and erectile dysfunction
Dorr RT, Wessells H, et al. (1996). Peptides
This pioneering clinical study evaluated Melanotan II's dual effects on skin pigmentation and erectile function in healthy male volunteers, establishing the foundation for melanocortin peptide research in both dermatology and sexual medicine. Researchers administered escalating subcutaneous doses ranging from 0.01 to 0.025 mg/kg and documented dose-dependent increases in skin melanin content measured by spectrophotometry, with visible tanning occurring within days of treatment initiation. The study simultaneously observed spontaneous penile erections in multiple subjects independent of sexual stimulation, leading to the unexpected discovery of Melanotan II's pro-erectile properties mediated through central melanocortin pathways. Analysis of side effect profiles identified transient nausea, facial flushing, and fatigue as common dose-limiting factors, informing subsequent dosing optimization research. These findings established Melanotan II as a multi-functional melanocortin agonist and led to the development of PT-141 (Bremelanotide) as a sexual dysfunction-focused derivative peptide.
Melanocortin peptides and their receptor in the regulation of pigmentation
Abdel-Malek ZA, Suzuki I, et al. (1999). Pigment Cell Research
This comprehensive mechanistic study investigated the molecular pathways through which Melanotan II and related melanocortin peptides regulate melanin synthesis in human melanocytes, providing crucial insight into MC1R signaling mechanisms. Using cultured human melanocytes from donors of varying skin types, researchers demonstrated that Melanotan II treatment significantly increased tyrosinase activity, melanin content, and dendricity in a dose-dependent manner across all skin phenotypes tested. The study revealed that MC1R activation triggers the cAMP-PKA-CREB signaling cascade, leading to upregulation of MITF transcription factor and downstream melanogenic enzymes including tyrosinase and tyrosinase-related proteins. Importantly, research showed that Melanotan II preferentially stimulates eumelanin over pheomelanin production, suggesting potential photoprotective benefits beyond cosmetic tanning effects. These findings established the molecular basis for melanocortin-mediated pigmentation and have informed ongoing research into therapeutic applications for pigmentary disorders and skin cancer prevention.
Melanotan II affects sexual arousal in female subjects
Diamond LE, Earle DC, et al. (2006). Journal of Sexual Medicine
This controlled clinical trial examined Melanotan II's effects on sexual arousal and desire in premenopausal women with female sexual arousal disorder, demonstrating the peptide's efficacy in female sexual dysfunction research. Researchers administered intranasal Melanotan II to study participants and measured physiological arousal response using vaginal photoplethysmography during erotic visual stimulation. Results showed significant increases in genital arousal parameters and subjective ratings of sexual desire compared to placebo, with effects occurring within 30-60 minutes of administration. The study documented that Melanotan II's sexual effects in women, like in men, are mediated through central nervous system melanocortin pathways rather than peripheral vascular mechanisms. These findings expanded understanding of melanocortin involvement in female sexual function and contributed to the development pathway for PT-141 as a treatment for hypoactive sexual desire disorder in women.