What it is
Melanotan II (MT-II) is a synthetic, cyclic and truncated analogue of alpha-melanocyte-stimulating hormone (α-MSH), one of two melanotropic peptides, with the linear melanotan I, that a University of Arizona group patented and took into human testing (Hadley and Dorr 2006). It entered research as a candidate tanning agent, and erections seen in its first human pilot study led to small studies in men with erectile dysfunction. PT-141 (bremelanotide) was later developed by Palatin Technologies as an MT-II analogue.
Mechanism of action
Melanotan II is described as a non-selective agonist of melanocortin receptors, the family of five receptors (MC1R to MC5R) that respond to α-MSH (Wessells et al. 2000). Hadley and Dorr (2006) describe the melanotan analogues as designed to be more potent, longer acting and more resistant to enzymatic breakdown than the native hormone. MC1R on pigment-producing melanocytes controls melanin production, which is thought to explain the increased skin pigmentation seen in the 1996 pilot study. Melanocortin receptors in the brain are thought to account for the other effects reported in men: spontaneous erections, increased sexual desire, stretching and yawning, and decreased appetite. Because the compound stimulates melanocytes, dermatologists have asked whether it can also drive changes in moles (melanocytic nevi). Cardones and Grichnik (2009) interpreted one case as evidence that synthetic α-MSH peptides can drive proliferation of abnormal melanocytes in predisposed people, but a causal link has not been established.
What it’s most studied for
Melanotan II was first studied as a tanning agent: the pilot study by Dorr et al. (1996) measured skin pigmentation in healthy men. Spontaneous erections were also reported in that study, and Wessells et al. then tested it in small crossover studies in men with psychogenic and organic erectile dysfunction between 1998 and 2000. Later clinical development focused on its analogue PT-141. Since then, most published work on melanotan II consists of dermatology case reports and reviews describing unlicensed use for tanning, with attention to new or changing moles and melanoma.
Notable findings
Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.
Pilot phase 1 study of tanning
Dorr et al. (1996) gave melanotan II or saline on alternating days to three healthy men, escalating the dose four times to find the maximally tolerated dose. Two of the three showed increased skin pigmentation, assessed both visually and with objective measurement. Mild nausea was the most common complaint, one subject had grade II somnolence and fatigue at the highest dose, and spontaneous erections were reported.
- Dose studied
- Subcutaneous injection starting at 0.01 mg/kg, given on weekdays over two weeks alternating with saline, with four dose escalations, healthy men (n=3)
[2] Dorr RT et al. · 1996 · PMID 8637402 ↗
Erections in psychogenic erectile dysfunction
Wessells et al. (1998) studied ten men with erectile dysfunction of no known organic cause, measuring erections with RigiScan monitoring. Clinically apparent erections developed in 8 of 10 men after melanotan II, and mean time at more than 80% tip rigidity was 38.0 minutes versus 3.0 minutes with placebo (p=0.0045). Nausea, stretching and yawning, and decreased appetite were reported more often after melanotan II than placebo; none required treatment.
- Dose studied
- 0.025 mg/kg by subcutaneous injection, compared with placebo injection in a crossover design, men with psychogenic erectile dysfunction
[3] Wessells H et al. · 1998 · PMID 9679884 ↗
Erections and desire in 20 men
Wessells et al. (2000) reported the group's human studies in 20 men with psychogenic or organic erectile dysfunction. Without sexual stimulation, melanotan II produced erections in 17 of 20 men, and increased sexual desire was reported after 13 of 19 melanotan II doses (68%) versus 4 of 21 placebo doses (19%, P<0.01). Nausea and yawning were common, and 12.9% of subjects had severe nausea at 0.025 mg/kg.
- Dose studied
- Subcutaneous injection, with the severe-nausea rate reported at 0.025 mg/kg, men with psychogenic or organic erectile dysfunction
[4] Wessells H et al. · 2000 · DOI 10.1038/sj.ijir.3900582 ↗
Changing moles after α-MSH analogue use
Cardones and Grichnik (2009) described a 40-year-old man with a history of melanoma and multiple dysplastic nevi who self-administered a synthetic α-MSH analogue. He developed new pigmented nevi with atypical features, and existing nevi darkened and showed signs of growth; the lesions lightened and lost those features after he stopped. The authors concluded that such peptides can drive proliferation of abnormal melanocytes in predisposed patients.
- Dose studied
- Self-administered synthetic α-MSH analogue; product content and amount not verified (case report)
[5] Cardones AR and Grichnik JM · 2009 · DOI 10.1001/archdermatol.2008.623 ↗
Melanoma after melanotan II and sunbed use
Hjuler and Lorentzen (2014) reported a 20-year-old woman with fair skin (Fitzpatrick type II) who presented with a suspicious dark lesion on the buttock that proved to be melanoma on excision. Three months earlier she had injected melanotan II for 3 to 4 weeks to enhance sunbed tanning. The authors described the melanoma as coinciding with melanocyte stimulation by melanotan II combined with sunbed use, without establishing that the drug caused it.
- Dose studied
- Self-injected melanotan II for 3 to 4 weeks alongside sunbed use; amount not reported in the sources reviewed (case report)
[6] Hjuler KF and Lorentzen HF · 2014 · DOI 10.1159/000356389 ↗
Study quality
Human evidence for melanotan II is weak: a pilot study in 3 healthy men and small crossover studies in 10 to 20 men with erectile dysfunction, all from one University of Arizona group in 1996 to 2000, plus later case reports. Its design rested on preclinical melanocortin receptor research. No controlled trial has tested it for tanning beyond the pilot study, and none of these studies enrolled women or followed participants long term. Adverse effects in the early studies were nausea (severe in 12.9% of subjects at 0.025 mg/kg), stretching and yawning, decreased appetite, somnolence and fatigue, and spontaneous erections. Evidence on unlicensed use comes from case reports, which describe new or changing moles and melanoma; Habbema et al. (2017) counted four reports of melanoma arising in existing moles during or shortly after melanotan use but noted that conclusive evidence of a causal link is lacking. Many cases also involved sunbed use, and the content of unlicensed products is unverified.
References
- 1Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. PMID 16412534
- 2Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences. PMID 8637402
- 3
- 4Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. International Journal of Impotence Research. DOI 10.1038/sj.ijir.3900582
- 5α-Melanocyte-stimulating hormone-induced eruptive nevi. Archives of Dermatology. DOI 10.1001/archdermatol.2008.623
- 6Melanoma associated with the use of melanotan-II. Dermatology. DOI 10.1159/000356389
- 7Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. International Journal of Dermatology. DOI 10.1111/ijd.13585
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