Melanotan 2 History: From the University of Arizona to Scenesse and Vyleesi

LynxLab · 24 October 2026 · 8 min read

How Hadley and Hruby's alpha-MSH analogues became Melanotan 1 and 2, the melanocortin receptor science behind them, and the two licensed drugs that followed.

Photo: Mikko Immonen, Unsplash

Melanotan 2 has an unusual family tree for a peptide now sold in gym changing rooms. It was designed in a university chemistry department, tested on frog skin, patented, trialled in a handful of volunteers and then abandoned by its inventors. Two of its close relatives went on to become licensed medicines. This is the history, with the dates and the names.

The story matters because melanotan 2 is often described online as if it were a finished drug. It is not. It is an early research compound from a programme that produced two approved products, neither of which is Melanotan 2, and it still carries an MHRA warning in the UK.

1980: a frog-skin assay and a hormone made 26 times more potent

The programme began at the University of Arizona in Tucson. Victor Hruby, a peptide chemist, and Mac Hadley, a biologist who studied pigment cells, were trying to understand why heating alpha-melanocyte stimulating hormone (alpha-MSH) with alkali made its effect on frog skin last longer.

Their answer, published in PNAS in October 1980, was that the heat treatment scrambled the chirality of two amino acids. When they built a synthetic version with norleucine at position 4 and D-phenylalanine at position 7, the new molecule resisted breakdown by serum enzymes and was 26 times as potent as natural alpha-MSH in a mouse melanoma adenylate cyclase assay (Sawyer et al., PNAS, 1980).

That molecule, [Nle4, D-Phe7]-alpha-MSH, is the compound later named Melanotan 1 and, much later, afamelanotide. A follow-up paper in Science in 1981 showed that a single injection darkened the skin of frogs for at least six weeks, against a few days for the natural hormone (Hadley et al., Science, 1981).

Melanotan 1 and Melanotan 2: two molecules from one team

Hadley and Robert Dorr, a pharmacologist, later wrote a history of the programme in the journal Peptides. They credit what they call "the Arizona Team": Hruby as chemist, Hadley as biologist, Dorr as pharmacologist and the dermatologist Norman Levine as clinician (Hadley and Dorr, Peptides, 2006).

The team made two commercial candidates. Melanotan 1 kept the full 13-amino-acid chain of alpha-MSH with the two substitutions. Melanotan 2 was a shorter, cyclic molecule: a seven-residue fragment of the hormone, positions 4 to 10, closed into a ring by a lactam bridge between an aspartate and a lysine.

The cyclic structure was the point. The ring locked the peptide into the shape the receptor prefers, which made mt2 a superpotent agonist in laboratory assays and more resistant to being broken down. Both compounds were patented, and the review records that Melanotan 1 was developed for skin tanning while Melanotan 2 was pursued for the diagnosis and treatment of male erectile dysfunction.

1992: the melanocortin receptors are cloned

For the first decade, nobody knew exactly what these peptides were binding to. That changed in August 1992 when Kathleen Mountjoy, Roger Cone and colleagues at the Vollum Institute in Oregon reported in Science that they had cloned the mouse and human MSH receptors and a human ACTH receptor (Mountjoy et al., Science, 1992).

The receptors turned out to be a subfamily of G protein-coupled receptors. The family eventually grew to five, MC1R to MC5R, each with a different job.

MC1R on melanocytes controls pigmentation. MC3R and MC4R in the brain are involved in appetite, energy balance and sexual function. MC2R is the ACTH receptor in the adrenal gland.

That map explained what the Arizona volunteers were about to experience. Melanotan 1 is fairly selective for MC1R, so its main effect is on pigment. Melanotan 2, the smaller cyclic molecule, is less choosy and also hits MC3R and MC4R, which is why its effects were never confined to the skin.

The 1990s volunteer studies and an unexpected finding

Dorr, Levine, Hruby and Hadley published the first human study of Melanotan 2 in Life Sciences in 1996. It was a pilot phase I trial in three healthy male volunteers, single-blind and placebo-controlled, with subcutaneous injections on alternating days over two weeks (Dorr et al., Life Sciences, 1996).

Two of the three men developed measurable darkening of the face, upper body and buttocks a week after dosing ended, recorded by reflectance measurement as well as by eye. The side effects were nausea at most dose levels, somnolence and fatigue at the highest, and a "stretching and yawning complex" that coincided with spontaneous penile erections lasting one to five hours.

That last observation redirected the programme. In 1998, Hunter Wessells and the same team ran a double-blind, placebo-controlled crossover study of the mt2 peptide in ten men with psychogenic erectile dysfunction, measuring rigidity with a RigiScan monitor. Eight of the ten developed erections after Melanotan 2 against 3.0 minutes of tip rigidity on placebo, with a mean of 38.0 minutes on the active compound (Wessells et al., Journal of Urology, 1998).

The reported side effects were the same as in 1996: nausea, stretching, yawning and loss of appetite. None needed treatment, but they were frequent enough that the molecule itself was not taken forward. Instead the rights were licensed and a modified version entered development under a new name.

2014 and 2019: Melanotan 1 becomes Scenesse

Melanotan 1 took the longer road. Licensed to an Australian company that became Clinuvel, it was renamed afamelanotide and developed not as a cosmetic tan but as a treatment for erythropoietic protoporphyria (EPP), a rare genetic disorder in which light exposure causes severe skin pain.

The European Medicines Agency granted it orphan designation on 8 May 2008. The European Commission authorised Scenesse across the EU on 22 December 2014, as a subcutaneous implant for the prevention of phototoxicity in adults with EPP (Scenesse EPAR, European Medicines Agency). The EMA page notes that the orphan status expired in December 2024 at the end of its ten years of market exclusivity.

The FDA approved Scenesse in October 2019. The US label describes a 16mg implant inserted under the skin every two months. In the main trial, CUV039, 93 subjects were enrolled and 48 received the implant; they recorded a median of 64.1 hours of pain-free direct sunlight over 180 days against 40.5 hours on placebo (Scenesse prescribing information, FDA, 2019).

The same label carries a warning that the drug may darken existing moles and freckles and recommends a full-body skin examination twice a year. Even the licensed, selective MC1R agonist comes with a pigmentation caveat.

2019: Melanotan 2 becomes Vyleesi

The erectile dysfunction finding went to Palatin Technologies in New Jersey, which produced bremelanotide, originally coded PT-141. Bremelanotide differs from Melanotan 2 by a single change at the end of the chain, a free acid in place of the amide, and the FDA label describes it as a synthetic cyclic heptapeptide and a melanocortin receptor agonist.

The FDA approved Vyleesi (bremelanotide injection) in June 2019 for premenopausal women with acquired, generalised hypoactive sexual desire disorder. The application was made by AMAG Pharmaceuticals under licence from Palatin.

The efficacy data came from two identical 24-week randomised, double-blind, placebo-controlled trials in 1,247 women. Nausea was reported by 40% of patients, and focal hyperpigmentation of the face, gums and breasts by 1%, with a higher risk in darker skin (Vyleesi prescribing information, FDA, 2019). The two side effects that stopped Melanotan 2 in 1998, nausea and unwanted pigmentation, are still on the label of its licensed successor.

Where that leaves Melanotan 2 today

Melanotan 2 itself was never licensed anywhere. The compound that reached patients for pigmentation was Melanotan 1, as an implant, for a rare disease, under specialist supervision. The compound that reached patients for sexual function was bremelanotide, a modified version.

What is sold as Melanotan 2 for tanning is therefore a research intermediate from a 30-year-old programme, with no completed safety studies and no regulator's approval. In the UK the MHRA classes injectable Melanotan II products as unauthorised medicines and has advised anyone who has used them to stop, a position set out in detail in the MHRA warnings on Melanotan 2 in the UK.

For laboratory work the picture is different. The molecule remains a standard tool for studying melanocortin receptors, which is why demand for melanotan 2 uk stock continues in research settings decades after the Arizona team moved on.

LynxLab stocks melanotan 2 10mg vials for research use at £24.99, tested to 99% purity with the certificate of analysis on the product page.

Frequently asked questions

Who invented Melanotan 2?

Melanotan 2 came out of the University of Arizona programme led by the chemist Victor Hruby and the biologist Mac Hadley, with the pharmacologist Robert Dorr and the dermatologist Norman Levine. Their first superpotent alpha-MSH analogue was published in 1980, and the first human study of Melanotan 2 appeared in 1996.

Is Melanotan 2 the same as afamelanotide or Scenesse?

No. Scenesse is afamelanotide, which is Melanotan 1, a linear 13-amino-acid peptide licensed in the EU in 2014 and the US in 2019 for erythropoietic protoporphyria. Melanotan 2 is a shorter cyclic peptide that was never licensed.

Is Melanotan 2 the same as bremelanotide or Vyleesi?

Not quite. Bremelanotide is a close derivative of Melanotan 2 with a free acid replacing the amide at the end of the chain. The FDA approved it as Vyleesi in June 2019 for hypoactive sexual desire disorder in premenopausal women.

Can researchers still buy Melanotan 2?

Yes. Anyone looking to buy melanotan 2 for laboratory use should expect a research-grade peptide with a batch certificate of analysis and no claims for human use. It is sold in the UK only as a laboratory reagent, and the MHRA warning on tanning products applies to anything presented for injection or use on a person.

Sources

Research use only

Melanotan 2 from LynxLab

10mg vials from £24.99. ≥99% purity, lab report on the page. Same-day dispatch, UK stock.

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