Melanotan-2

Research summary

Melanotan-2 (melanotan II, MT-II) is a synthetic cyclic seven-residue analog of alpha-melanocyte-stimulating hormone (alpha-MSH), designed at the University of Arizona. It activates several melanocortin receptors and is used in research as a reference agonist for pathways involved in pigmentation, appetite and sexual function. It has never been approved as a medicine, and Peptides Only supplies it for laboratory research only.

Also known as

Melanotan II · MT-II · MTII · Melanotan 2

Sequence

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

What is Melanotan-2?

Melanotan II is a lactam-bridged cyclic heptapeptide, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2, based on positions 4 to 10 of alpha-MSH. Its first human study described it as a superpotent melanotropic peptide¹, and its designers describe this family of analogs as long-acting and resistant to enzymatic breakdown².

It was one of two analogs developed by Hadley, Hruby, Dorr and colleagues in Tucson. The linear analog, melanotan I, went into clinical studies of skin tanning, while the cyclic, truncated melanotan II was studied for male erectile dysfunction. A later analog of melanotan II, PT-141, was taken forward by Palatin Technologies²; by 2007, as bremelanotide, it was the only melanocortin agent that had been studied clinically in both men and women³.

Melanocortin receptors and how MT-II is used

Melanocortin receptors are a family of five G protein-coupled receptors involved in pigmentation, steroid production and energy balance. Synthetic alpha-MSH derivatives, among them NDP-MSH (melanotan I), melanotan II and the antagonist SHU9119, have become standard tool compounds for studying them and served as scaffolds for FDA-approved drugs⁴.

MT-II acts on more than one subtype. Its skin-darkening effect in people¹ reflects the pigment pathway that alpha-MSH controls, while appetite research has focused on its agonist activity at the brain MC3 and MC4 receptors⁵.

What the research has examined

Pigmentation. In a small pilot phase I study, MT-II produced measurable darkening of the face, upper body and buttocks in two participants, assessed by reflectance a week after the last administration. Mild nausea was reported at most levels tested, somnolence and fatigue in one participant at the highest, and a stretching and yawning response accompanied spontaneous erections¹.

Erectile function. The same Arizona group then ran a double-blind, placebo-controlled crossover study in 10 men with psychogenic erectile dysfunction: 8 developed erections after MT-II, and the mean duration of high tip rigidity was 38 minutes, against 3 minutes on placebo. Nausea, stretching and yawning, and reduced appetite were more common than with placebo⁶.

Appetite. In mice, MT-II delivered into the brain ventricles suppressed feeding in four models of overeating, and the melanocortin antagonist SHU9119 blocked the effect. The experiment helped show that melanocortin neurons exert a tonic brake on feeding and explained the agouti obesity syndrome⁵.

Safety reports and regulatory status

MT-II never completed clinical development, yet products labeled as melanotan are sold through unregulated channels for tanning. A 2017 review of that use summarized case reports of changes in existing moles, new and sometimes dysplastic nevi, and four melanomas arising during or shortly after melanotan use. It stressed that conclusive evidence of causation is lacking, and noted that multiple national health organizations have issued safety warnings about melanotan I and II⁷. In the UK, the Medicines and Healthcare products Regulatory Agency has highlighted the potential impurity of these unregulated products⁸.

In one documented case, a man with a history of melanoma and dysplastic nevi developed crops of new atypical nevi after self-administering a synthetic alpha-MSH, and they faded after he stopped⁹. Forensic laboratories have also had to characterize seized black-market MT-II and bremelanotide without reference standards¹⁰, a reminder that identity cannot be assumed without analytical testing.

Limitations of the evidence

• Human data are limited to small pilot and crossover studies and to uncontrolled case reports.
• Key mechanistic findings come from rodents given MT-II directly into the brain, which does not reflect systemic exposure.
• Because MT-II acts at several receptor subtypes, a given effect is hard to assign to one receptor without selective antagonists such as SHU9119 or knockout models^4,5.

Sourcing Melanotan-2 for research

Peptides Only supplies Melanotan-2 as a lyophilized powder for laboratory research only. Every lot ships with a lot-matched certificate of analysis from an independent lab, reporting HPLC purity and mass-spectrometry identity, published in our COA library; our testing standard explains what is checked. Its closest relative is PT-141, and the article PT-141 vs Melanotan-2 compares the two in detail.

Further reading

• PT-141 vs Melanotan-2: How Bremelanotide and Melanotan II Compare