Melanotan 1 vs Melanotan 2: differences, research and regulatory status
Melanotan 1 and Melanotan 2 are synthetic versions of alpha-melanocyte-stimulating hormone (α-MSH), the hormone that tells skin cells to make melanin. Both were developed at the University of Arizona in the 1980s and 1990s while looking for a way to tan the skin without sunlight. They ended up on very different paths: Melanotan 1 became an approved medicine for a rare light-sensitivity disease, while Melanotan 2 led to an approved drug for a completely different use. This guide compares them.
At a glance
| Melanotan 1 | Melanotan 2 | |
|---|---|---|
| Other names | Afamelanotide, MT-I | MT-II |
| Structure | Linear, 13 amino acids: α-MSH with two substitutions ([Nle4, D-Phe7]-α-MSH) | Cyclic, 7 amino acids: a shortened ring-shaped analogue of α-MSH |
| Receptors | Mainly MC1R, the pigment receptor | Several: MC1R, MC3R, MC4R and MC5R |
| Main effect studied | Pigmentation and protection from light | Pigmentation, plus effects on appetite and sexual function through brain receptors |
| Approved medicine | Yes: Scenesse implant, for erythropoietic protoporphyria (EU 2014, US 2019) | No. A related compound, bremelanotide, is approved in the US |
How they work
α-MSH acts on a family of five melanocortin receptors (MC1R to MC5R), each found in different tissues. MC1R sits on melanocytes, the pigment cells of the skin; when activated, it shifts melanin production towards eumelanin, the dark brown pigment that absorbs ultraviolet light. MC3R and MC4R are found mainly in the brain, where they help control appetite, energy balance and sexual function.
Natural α-MSH breaks down within minutes. The Arizona group, led by Mac Hadley and Victor Hruby, found that replacing two amino acids made a version many times more potent and far longer lasting: Melanotan 1. Melanotan 2 was designed afterwards as a smaller, ring-shaped molecule. Its ring structure makes it even more stable, but also less selective: it activates the brain receptors as well as the pigment receptor, which explains why its effects go well beyond the skin.
Melanotan 1: from tanning to an approved medicine
Melanotan 1 was developed as afamelanotide by the company Clinuvel for erythropoietic protoporphyria (EPP), a rare inherited disease in which light exposure causes severe skin pain. In a randomised controlled trial published in 2015, people with EPP receiving afamelanotide implants could spend significantly more time in direct sunlight without pain than those on placebo.
It was approved by the European Commission in 2014 and by the US FDA in 2019, as a 16 mg implant placed under the skin by a doctor in specialist centres. It is not sold in pharmacies and is not authorised for cosmetic tanning anywhere. It has also been studied in vitiligo, combined with light therapy.
Melanotan 2: broader effects and a spin-off drug
Early human studies of Melanotan 2 in the 1990s confirmed that it darkened the skin, but they also recorded side effects such as nausea, facial flushing, yawning and stretching and, in men, spontaneous erections. A small placebo-controlled study then looked at the erection effect directly, in men with erectile dysfunction.
That side effect became its own research line. Bremelanotide (also called PT-141) is a closely related cyclic peptide that acts mainly on MC3R and MC4R in the brain. It was approved by the FDA in 2019 as Vyleesi, for low sexual desire in premenopausal women. It is not approved in the EU.
Melanotan 2 itself has never been approved as a medicine in any country.
Safety reports
Both compounds have been widely misused as unlicensed "tanning injections" bought online. A 2017 review collected case reports linking this unregulated use to changes in existing moles, new atypical moles and, in a few cases, melanoma appearing during or soon after use. The authors note that case reports cannot prove cause and effect, but that rapid changes in pigmented spots can also make skin cancer harder to recognise. Several national health authorities in Europe and elsewhere have issued warnings against these products.
Legal status in Europe
- Afamelanotide is a prescription-only medicine for EPP, given as an implant in specialist centres. It is not available in pharmacies for any other use.
- Melanotan 2 is not authorised as a medicine anywhere, and selling it for human use is illegal in the EU.
- Research peptides sold as Melanotan 1 or Melanotan 2, including ours, are supplied for laboratory research only and are not for human use.
Which one for which research
- Melanotan 1 suits research focused on MC1R and pigmentation, where a selective agonist is needed.
- Melanotan 2 suits research comparing melanocortin receptors, or involving the central receptors MC3R and MC4R.
- PT-141 is the compound to use when the focus is the central melanocortin system without the skin effect as the main target.
Handling
Both are supplied as lyophilised powder. Keep unopened vials in the freezer, protected from light, and reconstituted solutions in the refrigerator. See our storage guide and our guide to reconstitution water.
References
- Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides 2006;27(4):921–930.
- Langendonk JG et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med 2015;373(1):48–59.
- Dorr RT et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58(20):1777–1784.
- Wessells H et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol 1998;160(2):389–393.
- Habbema L et al. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol 2017;56(10):975–980.
- US Food and Drug Administration. Scenesse (afamelanotide) implant, approval 2019; Vyleesi (bremelanotide) injection, prescribing information, 2019.