Melanotan 2

Melanotan II (also written melanotan 2, MT-II or MT2) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH): Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, with a lactam bridge between Asp and Lys and a C-terminal amide (PubChem CID 92432). The compound was first reported in a 1989 design study of cyclic lactam α-MSH(4-10) analogs (Al-Obeidi et al., 1989) and acts as a nonselective melanocortin receptor agonist (Wessells et al., 2000).

It is not for use in people, and this page makes no claim of any cosmetic or other effect.

Published work on melanotan II falls into six areas. Each summary below states the model used. The human studies were small early-phase trials published between 1996 and 2000, not studies of the research material sold here.

Design and receptor pharmacology

In the 1989 study, the Asp5 to Lys10 lactam analog that corresponds to MT-II was about 90 times as potent as α-MSH in a lizard skin bioassay, and analogs with this 23-membered ring showed prolonged activity, while larger or smaller rings reduced potency (Al-Obeidi et al., 1989).

On cells expressing human MC1, MC3, MC4 and MC5 receptors, MT-II and the related lactam SHU9119 bound with higher overall affinity than cyclic disulfide analogs, and replacing D-Phe7 with D-Nal(2')7 shifted selectivity toward MC4 (Schiöth et al., 1997). An alanine scan at human MC3, MC4 and MC5 receptors found that replacing His left affinity and potency largely unchanged, replacing Arg cut potency about 100-fold and replacing D-Phe or Trp abolished activity at micromolar concentrations (Bednarek et al., 1999).

Feeding, energy balance and stress models in rodents

In mice, intracerebroventricular MT-II inhibited feeding in four models of hyperphagia, including fasted, ob/ob and A(Y) mice, and the melanocortin antagonist SHU9119 blocked the effect. SHU9119 alone increased nocturnal and fast-induced feeding, which the authors took as evidence that melanocortin neurons tonically inhibit feeding (Fan et al., 1997). In male rats under chronic unpredictable stress, MT-II, tested alongside Semax, reversed or attenuated anhedonia, suppression of body-weight gain, adrenal hypertrophy and the fall in hippocampal BDNF (Inozemtseva et al., 2024).

Sexual behavior models in rats

In anesthetized rats, MT-II given systemically or into the paraventricular nucleus of the hypothalamus elicited erectile events and shortened their latency, and systemic administration enhanced erectile responses to cavernous nerve stimulation, an effect abolished by removing the lumbar paravertebral sympathetic chain (Giuliano et al., 2006). In ovariectomized female rats primed with estradiol and progesterone, MT-II increased hops and darts and ear wiggling without changing pacing or lordosis, and it had no effect in rats primed with estradiol alone (Rössler et al., 2006).

Early clinical studies

A pilot phase 1 study in three healthy men reported mild nausea at most levels tested, somnolence and fatigue in one participant and a stretching and yawning complex that coincided with spontaneous penile erections; two participants showed increased skin pigmentation measured by reflectance (Dorr et al., 1996).

In a placebo-controlled crossover study of ten men with psychogenic erectile dysfunction, eight developed erections after MT-II, with nausea, stretching, yawning and decreased appetite reported more often than with placebo (Wessells et al., 1998). The same group's review of 20 men with psychogenic or organic erectile dysfunction reported erections in 17 and frequent nausea and yawning (Wessells et al., 2000).

Physicochemical and analytical studies

Preformulation work measured pKa values of 6.54 for histidine and 11.72 for arginine and an octanol partition coefficient of 2.82 at pH 7.35 (Lan et al., 1994). An LC-MS/MS method quantified MT-II in mouse plasma and brain down to 0.5 ng/mL and 2.5 ng/g and showed rapid plasma clearance with low brain penetration (Hatziieremia et al., 2007).

LC-UV-MS/MS testing of vials bought online found 4.32 to 8.84 mg of peptide against a 10 mg label (Breindahl et al., 2015). High-resolution mass spectrometry has also characterized melanotan II and bremelanotide in confiscated samples (Mestria et al., 2021).