Melanotan II is a cyclic lactam analog of the melanocortin alpha-Melanocyte Stimulating Hormone (α-MSH), a multifunctional peptide that regulates a broad array of physiological functions, including the stimulation of melanogenesis and aphrodisiac effects via melanocyte receptor activation. Melanotan II has not been approved for human use outside of clinical trials; however, it has been studied extensively for use in protecting against the harmful effects of ultraviolet radiation from sunlight due to its melanogenesis stimulating properties. Resultantly, it was conceived that Melanotan II could be used to stimulate skin melanogenesis and development as a photoprotective or cosmetic drug. Additionally, Melanotan II and a similar α-MSH analogue, know as PT-141 or Bremelanotide, have been studied at length as a potential remedy for the treatment of sexual dysfunction; specifically, male erectile dysfunction.
The initial creation of the synthetic Melanotan II peptide can be credited to the University of Arizona. During the course of scientific research aimed at developing a defense against skin cancer, focus was placed on developing a method of stimulating natural melanogenesis or the natural production of melanin in the skin. Initially, University of Arizona scientists attempted to directly administer the naturally occurring hormone α-MSH in order to elicit this desired result.
Although this strategy exhibited promising results, it was determined that the naturally occurring α-MSH had a prohibitively short half-life to be of realistic use as a possible future therapeutic remedy. However, the positive results gleaned from α-MSH administration encouraged further research into the development of a compound that would exhibit similarly beneficial effects whilst possessing an extended half-life for functional therapeutic utilization. Subsequent research and development yielded the synthesis of Melanotan-1, a peptide vastly more powerful in its melanogenesis-promoting effects than α-MSH. After additional studies, researchers developed Melanotan II, a compound believed to be 1,000 times more powerful than α-MSH.
It is known that the effects of α-MSH are mediated by melanocortin receptors. MC1R is expressed in skin cells and has a high affinity for α-MSH and is the main receptor by which α-MSH signals. Based on this fundamental information, and observations of how α-MSH impacts melanomic cells, one study has hypothesized that "α-MSH acts initially to reduce initial tumor spread, but then paradoxically protects those cells that escape from the primary tumor." As an analog of α-MSH, it is logical to believe that Melanotan II may have similar effects.
Melanotan-1, the precusor to Melanotan II, would eventually be licensed for commercialization as a tanning agent and has been in development for use as a potential "therapeutic tan," with minimal need for prolonged sun exposure. In the initial clinical testing of Melanotan II, an immediate and unexpected response was noted. The main subject experienced an erection shortly after administration. It was suggested that Melanotan II "may prove equally effective in women" as a "treatment of female sexual dysfunction. At least one study has observed that administration of Melanotan II may increase sexual desire, which should warrant further "investigation of centrally acting agents on disorders of sexual desire."
Theoretically, Melanotan II may enhance sexual function in males (erectile activity) and females (increased levels of sexual desire and genital arousal). Unlike other sexual-enhancement drugs, it is hypothesizedd that Melanotan II works at a neurological level, eliciting a more "natural" sexual response with minimal side effects. It was suggested that Melanotan II "may prove equally effective in women" as a "treatment of female sexual dysfunction. At least one study has observed that administration of Melanotan II may increase sexual desire, which should warrant further "investigation of centrally acting agents on disorders of sexual desire."
A pilot Phase I clinical trial published in 1996 conducted on three males by the College of Medicine, Pharmacology Department, University of Arizona in Tucson, Arizona reported that "Melanotan II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection." The side effects reported were mild nausea and a "stretching and yawning complex" that correlated with spontaneous penile erections.
The Department of Pharmacology, University of Arizona College of Medicine published a study in 1998 that involved ten men who suffered from psychogenic erectile dysfunction. Their trial concluded that "Melanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dosage of 0.025 mg./kg."
A clinical study published in 2000 of 20 men with psychogenic and organic erectile dysfunction conducted at the Section of Urology of The University of Arizona College of Medicine concluded that "Melanotan II is a potent initiator of penile erection in men with erectile dysfunction."
A study at the University of Arizona’s College of Medicine further demonstrates Melanotan II’s libido-enhancing properties. The study, which focused on ten men with psychogenic erectile dysfunction, reached the conclusion that Melanotan II is a powerful stimulator of erections in male subjects suffering from this ailment. Importantly, the researchers conducting the study also concluded that the peptide had mild, if any, side effects during the course of the trial.
Melanotan II studies conducted on laboratory mice have also demonstrated the peptides profound effect on lipid metabolism and caloric intake. Specifically, six days of administration in laboratory mice resulted in a significant reduction in body weight and fatty tissue along with a decrease in the amount of calories ingested by the mice. Moreover, it was also demonstrated that Melanotan II administration promoted an increase in the utilization of oxygen in the obese subjects. Studies have also suggested that Melanotan II administration may enhance catabolism of fat in muscle tissue and promote an improvement in cholesterol metabolism as well.
Studies have already shown the importance of melanocortins within the nervous system, but one study "intended to further explore the possible beneficial effects of [Melanotan II] in peripheral nerve regeneration and neuroprotection" in rats. Therein, the data demonstrated that Melanotan II "enhanced recovery of sensory function following a crush lesion of the sciatic nerve" in the subect rats, and further that "Melanotan II protected against neuropathy induced by cisplatin." One study has also stated that it appears as though Melanaton II "increases fat loss (catabolism) in skeletal muscle, and improves glucose and cholesterol metabolism" in specific rats.
 Hadley, Mac E., et al. "Discovery and development of novel melanogenic drugs." Pharmaceutical Discovery and Development. Springer US, 1998. 575-595.  Eves, Paula C., Sheila MacNeil, and John W. Haycock. "α-Melanocyte stimulating hormone and human melanoma." Peptides 27.2 (2006): 444-452.  See Footnote 2.  See Footnote 2.  See Footnote 1.  Wessells, Hunter, et al. "Effect of an α-MSH analog on penile erection and sexual desire in men." Urology 56.4 (2000): 641-646.  F.L. Strand, L.A. Zuccarelli, S.E. Alves Melanotropins as growth factors Ann. N. Y. Acad. Sci., 31 (680) (1993), pp. 29-50.  Ter Laak, Mariel P., et al. "Melanotan-II promotes peripheral nerve regeneration ... in the rat." European journal of pharmacology 462.1 (2003): 179-183.  See Note 4.  Li, G., et al. "Anorexic and enhanced thermogenic responses to melanotan II..." Journal of endocrinology 182.1 (2004): 123-132.