Melanocortins are a family of five G-protein-coupled receptors — MC1 through MC5 — that the endogenous peptide α-melanocyte-stimulating hormone (α-MSH) and its synthetic analogues act on. The four peptides compared here are all analogues of that same natural ligand, but they are not interchangeable: they differ in length, receptor selectivity, licensed indication and, critically, legal status in the UK.

This explainer is written for research literacy. It describes what each compound is, what the published evidence does and does not support, and how each is treated under UK medicines law. It is not consumption advice, and none of these compounds should be understood as being available for personal use.

One receptor family, four different outcomes

MC1R sits on melanocytes in the skin and governs eumelanin production; it is the target of the tanning-related peptides. MC3R and MC4R are expressed centrally, including in the hypothalamus, where they form part of the leptin–melanocortin pathway that regulates appetite and energy homeostasis. MC4R agonism is therefore the mechanism behind both the appetite-modulating medicines in this class and the centrally mediated side effects reported with the older tanning peptides.

Afamelanotide (Scenesse; historically "Melanotan I")

Afamelanotide is a 13-amino-acid synthetic analogue of α-MSH carrying two substitutions (Nle4, D-Phe7) that make it resistant to degradation and give it high selectivity for MC1R. It is delivered as a subcutaneous bioresorbable implant. In the UK it is a prescription-only medicine (POM); the European Commission authorised it on 22 December 2014, under exceptional circumstances, for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare inherited disorder of haem synthesis that causes severe light sensitivity.

The pivotal evidence in EPP showed that afamelanotide increased the time patients could spend in direct sunlight on pain-free days over a six-month period. Earlier volunteer work in fair-skinned adults found the peptide significantly increased pigmentation and reduced markers of ultraviolet-induced damage (Barnetson et al., 2006). Access remains restricted: in Scotland the Scottish Medicines Consortium did not recommend routine use, and from February 2021 the medicine could be prescribed only within the ultra-orphan pathway while further evidence is generated.

There is no licensed cosmetic tanning indication. Products sold online as "Melanotan I" are not Scenesse and have not been assessed for identity, purity, safety or efficacy.

Melanotan II

Melanotan II is a shorter, cyclic α-MSH analogue. It is less selective than afamelanotide, binding MC1R, MC3R, MC4R and MC5R. Its MC4R activity produces the central effects — nausea, flushing and sexual side effects — documented in early human studies, which is also why it was investigated as a prosexual agent before bremelanotide.

Melanotan II has never held a marketing authorisation in the UK or, to our knowledge, anywhere else. The MHRA's position is that Melanotan products fall within the definition of a medicinal product under the Human Medicines Regulations 2012; because no Melanotan product holds a UK marketing authorisation, advertising, sale and supply are in breach of regulatory requirements. The Agency has warned the public against "tan jab" products, contacted suppliers, and worked with internet service providers to suspend more than 100 trading websites. As of June 2014 the MHRA had received 22 adverse drug reaction reports linked to Melanotan products, describing 93 reactions.

The peer-reviewed human evidence base is thin: mostly small, uncontrolled or observational work, with no placebo-controlled trial establishing efficacy or a tolerable safety profile. On this site it sits at the lowest evidence grade.

Bremelanotide (PT-141)

Bremelanotide is a cyclic α-MSH analogue developed originally as a tanning agent and later repositioned as a centrally acting MC4R agonist. It holds a US marketing authorisation granted in 2019 but no UK marketing authorisation — so in the UK it is not a licensed medicine.

Its pivotal programme reported statistically significant improvements on co-primary endpoints in premenopausal women, but effect sizes were modest, a substantial proportion of participants did not respond, and tolerability was limited by nausea, flushing and transient rises in blood pressure. The gap between statistical significance and clinical meaningfulness is exactly the kind of uncertainty this publication tries to state plainly rather than resolve for the reader.

Setmelanotide (Imcivree)

Setmelanotide is a selective MC4R agonist given as a daily subcutaneous injection. Unlike the tanning peptides, its action is deliberately central: it is designed to restore signalling in the leptin–melanocortin pathway in patients whose genetic defects sit upstream of MC4R.

In the UK it holds a marketing authorisation for the treatment of obesity and the control of hunger in genetically confirmed Bardet–Biedl syndrome, or loss-of-function biallelic POMC (including PCSK1) or LEPR deficiency, in adults and children aged 2 and above. The UK authorisation was first granted in 2021 for POMC, PCSK1 and LEPR deficiency obesity, extended to Bardet–Biedl syndrome in 2022, and widened in 2024 to include children as young as 2. On 11 August 2026 the MHRA further expanded the authorisation to cover adults and children aged 4 and above with acquired hypothalamic obesity due to hypothalamic injury or impairment, and granted orphan drug designation for that indication.

The European assessment of setmelanotide noted that all primary and key secondary endpoints were met in the pivotal RM-493-012 and RM-493-015 trials, while also flagging the small patient numbers and some inconsistency in the LEPR cohort. Setmelanotide is not licensed for common, polygenic obesity; it is prescribed only through specialist pathways for the defined genetic or hypothalamic populations.

What the evidence grades reflect

Afamelanotide and setmelanotide are the two members of this class with randomised, endpoint-driven human data supporting a specific licensed indication — evidence best described as moderate within a narrow population. Bremelanotide has Phase 3 data but in an indication and jurisdiction that do not extend to the UK. Melanotan II has no controlled human evidence at all and remains unlicensed; its record is dominated by pharmacovigilance reports rather than trials.

The UK legal position

All of these compounds are peptides regulated as medicinal products where they are supplied for a medicinal purpose. The relevant framework is the Medicines Act 1968, the Human Medicines Regulations 2012 and MHRA guidance. A product without a UK marketing authorisation may not lawfully be advertised or sold for human use. "Research use only" labelling does not license personal use, and selling a peptide as a research chemical while promoting it for human use is itself the conduct the MHRA has acted against.

This publication describes research findings and regulatory status only. It gives no dosing, administration or personal-use information, and nothing here should be read as a claim that any peptide treats, cures or prevents a condition.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.