Melanotan II (revision 7)

Melanotan II is a synthetic cyclic analogue of α-melanocyte-stimulating hormone and a non-selective agonist at melanocortin receptors. It is not approved in any jurisdiction and is distributed as a research chemical.^[1]

Non-selectivity is the defining property. Agonism at MC1R produces melanogenesis, the effect for which it is sought; agonism at MC4R affects appetite and sexual function; agonism at MC3R and MC5R contributes further effects. A single compound producing all of them simultaneously is a pharmacological blunt instrument.^[1]

Documented harms include nausea and vomiting, spontaneous erections, darkening and change of pigmented lesions, and case reports of melanoma diagnosed in users — the last of which is confounded by the underlying reason people seek tanning and by increased dermatological attention.^[2]

The melanocortin system comprises five receptors with distinct distributions. MC1R on melanocytes controls the switch between pheomelanin and eumelanin synthesis; MC4R in the hypothalamus is central to appetite regulation and is the target of approved anti-obesity compounds in rare genetic conditions. See Arcuate nucleus.^[3]

Melanotan II activates all of these. Selective compounds developed subsequently — bremelanotide for sexual dysfunction, and MC4R-directed agents for genetic obesity — represent the pharmacological correction of that non-selectivity.^[1]

Effects on appetite are real and are the reason the compound appears in weight-related discussion, but they are accompanied by every other melanocortin effect at the same time.^[3]