Melanotan-2

What Melanotan II is and how it works

Melanotan II is a cyclic seven-residue peptide derived from alpha-melanocyte-stimulating hormone. It came out of a University of Arizona programme in the 1980s, where the physiologist Mac Hadley, the chemist Victor Hruby and the pharmacologist Robert Dorr sought a way to darken skin without ultraviolet exposure, reasoning that this might reduce skin cancer risk. Their first compound, melanotan I, was linear. Melanotan II followed as a smaller ring closed by a lactam bridge, more potent in laboratory assays and more resistant to enzymatic breakdown.

The ring binds melanocortin receptors, a family of five with distinct jobs. MC1R on melanocytes drives production of the dark pigment eumelanin. MC2R is the adrenal receptor for ACTH. MC3R and MC4R sit largely in the brain and take part in energy balance and appetite, and MC4R is also involved in sexual function. MC5R is found in exocrine glands. Melanotan II is an agonist at MC1R, MC3R, MC4R and MC5R, so one dose reaches skin, appetite and sexual pathways at once. That lack of selectivity is the central fact about the molecule, and it is why its effects cannot be separated from one another.

Its selectivity problem is also its legacy. Unexpected erections in the first volunteers opened a separate line of work that produced bremelanotide, better known as PT-141. The linear melanotan I became afamelanotide, an authorised medicine for a rare light-sensitivity disorder. Melanotan II itself never completed a development programme.

What the research on Melanotan II shows

The human data are small and old. In a pilot phase I study (Dorr et al., Life Sciences, 1996), three healthy men received subcutaneous Melanotan II or saline on alternating weekdays for two weeks. Two developed increased pigmentation of the face, upper body and buttocks, still measurable a week after dosing ended. The study also recorded mild nausea at most dose levels, a stretching and yawning complex, spontaneous erections lasting one to five hours, and somnolence at the highest dose. Three subjects is a tolerability exercise, not evidence of efficacy or safety.

Wessells and colleagues (Journal of Urology, 1998) then gave Melanotan II to ten men with erectile dysfunction of no known organic cause, in a double-blind, placebo-controlled crossover study with instrumented monitoring. Eight of the ten developed clinically apparent erections, and mean duration of tip rigidity above 80% was 38 minutes against 3 minutes on placebo. Nausea, yawning and reduced appetite were more frequent on the peptide.

Animal work is where the compound earned its place in the literature. Fan and colleagues (Nature, 1997) showed that Melanotan II injected into the brain ventricles suppressed feeding in several mouse models of overeating, a result that helped put MC4R at the centre of appetite research. It remains a standard tool compound for central melanocortin signalling, which is a different thing from being a candidate medicine. Almost everything else published about its use in people is case reports, which describe harms but cannot measure their frequency.

Melanotan II doses used in published research

The human figures come from two small studies in the 1990s that explored tolerability in a handful of men. They are not a validated dose: Melanotan II has no approved human use anywhere, and the 1996 escalation stopped where side effects appeared. The table records published study designs; it is not instructions for use in people.

Melanotan II safety and side effects

The safety picture comes from two small studies in the 1990s and from case reports of unsupervised use.

• Nausea and flushing. Nausea was the most consistent effect in the controlled studies. Facial flushing is commonly described by users and is a recognised melanocortin effect; with bremelanotide it affected about a fifth of trial participants.
• Spontaneous erections. Acting through MC4R, the peptide can trigger erections without sexual stimulation. Overdose has been linked to priapism, a medical emergency.
• Yawning, stretching and appetite loss. Central melanocortin effects, present in both controlled studies and dose related.
• New or changing moles. Darkening of existing moles and eruption of new ones have been reported, and there are published case reports of melanoma in users. Case reports cannot establish cause, so the question of long-term skin risk is open rather than answered.
• Systemic toxicity. A 2012 case report described rhabdomyolysis, a heart rate peaking at 146 beats per minute and kidney dysfunction in a man who injected 6 mg at once.

Regulatory status of Melanotan II in Europe

Melanotan II is not authorised as a medicine in the EU or anywhere else. Several European medicines regulators have warned the public about unlicensed melanotan injections and nasal sprays, among them the UK medicines agency and the Irish Medicines Board, now the HPRA, citing unknown side effects and uncertain product content. In EU law such a substance is a medicinal product and needs authorisation, so material offered in Europe can only be sold as a research chemical. Rules on possession and personal import differ between member states, as our buying guide sets out.

The contrast with afamelanotide is the useful one. Afamelanotide, formerly melanotan I, was authorised in the EU in 2014 as Scenesse, an implant for adults with erythropoietic protoporphyria, an inherited disorder in which sunlight causes severe pain. It is a different, linear molecule, it went through controlled trials, and it is prescribed in specialist porphyria centres. Melanotan II has none of that behind it. For athletes, the WADA list bans under S0 any pharmacological substance without approval for human therapeutic use, a description that fits Melanotan II exactly.

Sourcing and quality of Melanotan II

King Peptides stocks Melanotan II 10 mg for laboratory research. The certificate of analysis should show HPLC purity of 99% or higher and a mass spectrum matching 1024.2 Da, with the lot number the same as the one on the vial. One detail repays attention: bremelanotide weighs 1025.2 Da, about 1 Da more, so telling the two apart needs a properly resolved spectrum rather than a rounded figure. Our guide to certificates of analysis covers the other checks.

Parcels are dispatched from the Netherlands, with a shop estimate of 1–2 business days within the Netherlands and 3–5 business days elsewhere in the EU and no customs formalities inside the union; buyers in the UK, Switzerland or Norway can face import rules and duties. Packaging is neutral and tracked, and buyers confirm at checkout that they are 18 or older and ordering for research. Our storage guide covers the lyophilised powder at the −20 °C the panel specifies.

Melanotan II: frequently asked questions

Is Melanotan II the same as afamelanotide? No. Afamelanotide is melanotan I, authorised in the EU as Scenesse for a rare light-sensitivity disorder. Melanotan II is a cyclic, non-selective agonist with pronounced effects on appetite and sexual function, authorised nowhere.

Why does it affect appetite and sexual function? Because it activates MC3R and MC4R in the brain as well as MC1R in the skin. Bremelanotide, now PT-141, was developed from it and is approved in the United States; Melanotan II is approved for nothing.

Did the original skin cancer idea work out? It was the motivation in Arizona, and it was never demonstrated. No study has shown that pigmentation induced this way protects against skin cancer, while case reports of melanoma in users point the other way.