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Melanotan II (MT-II, MT2) is a synthetic partial analog of alpha melanocyte-stimulating hormone (a-MSH), one of the melanotropin peptides. Melanocortins are commonly associated with pigmentation, sexual function, lipolysis and oxidation of fatty tissues, appetite and meal frequency, and interplay with the leptin system. Melanotan II has been investigated for years as a treatment for a variety of uses or conditions such as safer tanning or UV chemoprevention, sexual dysfunction, and obesity.
Physiologically and pharmaceutically, melanotropin peptides primarily act through the melanocortin (MC) system of receptors. The leptin system’s primary mechanism of action in the brain is vis-a-vis the melanocortin system.
A pilot trial study using human subjects (Dorr et al, 1996) noted significant change in pigmentation ( darkening) after five applications of MTII (applied every other day via subcutaneous injection) when measured by visual perception as well as by quantitative reflection. Dorr et al also noted penile erection consistently occurred concomitantly with "stretching and yawning" between one and five hours after application of MTII in their study. The next most common side-effect at most MTII dosage levels was nausea; although no treatment was allowed for nausea, all subjects volunteered to continue the trials for the duration of the two-week study.
In a trial focused specifically on erections in males and therapeutic potential (Wessells et al, 1998) the authors concluded:
Melanotan-II is a potent initiator of erections in men with psychogenic erections in men with psychogenic erectile dysfunctions and has manageable side effects at a dose of 0.025mg/kg...: In 8 of 10 men treated with Melanotan-II clinically apparent erections developed. Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo (p=0.0045). Transient side effects of nausea, stretching and yawning, and decreased appetite were reported more frequently after injections of Melanotan-II than placebo but none required treatment" .
Melanotan II exhibits several different mechanisms that make it an attractive candidate for development as an obesity treatment. Through the MC3R and MC4R, MT2 exhibits an anorectic and thermogenic effect, even where receptors are relatively absent; further benefits may occur due to leptin system interplay. Additionally, the pro-erectile effects it exhibits could help address erectile dysfunction, a common issue among obese men.
 Hruby VJ, Lu D, Sharma SD, Castrucci AL, Kesterson RA, al-Obeidi FA, et al. Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4–10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J Med Chem 1995;38(18):3454–61.
 Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT- 141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci 2003;994:96–102.
 PEPTIDES IN ENERGY BALANCE AND OBESITY (Book), Gema Frühbeck (ed.), CAB International 2009, Subsection: Anorexigenic Peptides, Perboni, S., Ueno, G., Mantovani, and Inui, A. pp. 45-47
Dorr R.T., Lines R, Levine N., Brooks C., Xiang L., Hruby V.J., Hadley M.E. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci, 1996;58(20), pp.1777-84.
 Wessells H., Fuciarelli K., Hansen J., Hadley M.E., Hruby V.J., Dorr R., Levine N. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998 Aug;160(2): pp. 389-93.
Li G, Zhang Y, Wilsey JT, Scarpace PJ. Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression. J Endocrinol. 2004 Jul;182(1):123-32.