Melanotan II: Circular Melanocortin Analog for Tanning and Libido Stimulation
Melanotan II is a highly potent circular peptide engineered to stimulate melanogenesis and sexual arousal through the activation of central and peripheral melanocortin receptors.
Structural Parameters of Melanotan II
| Property | Value and Specification | References |
|---|---|---|
| CAS Number | 121062-08-6 (free base) | |
| Molecular Formula | C50H69N15O9 (free base) | |
| Molecular Weight | 1024.18 g/mol (free base) | |
| Chemical Structure | Cyclic lactam-modified heptapeptide | |
| Sequence | Ac-Nle-cyclo-NH2 |
Origin, History, and Research Stage
Melanotan II was synthesized at the University of Arizona in the late 1980s by Victor J. Hruby and Mac E. Hadley. It was designed as a shorter, cyclized successor to Melanotan I. Palatin Technologies acquired the rights but eventually shifted focus to Bremelanotide (PT-141). Melanotan II is not approved by the US FDA, EMA, or other regulatory bodies for human use, and health agencies have warned against its use since 2007. It remains widely used in research on melanocortin pathways, social behavior, and erectile function.
Mechanism of Action and Pharmacokinetics
Melanotan II is a cyclic analog of alpha-MSH. Its cyclic structure, established via a lactam bridge between Asp3 and Lys8, provides structural rigidity that protects it from enzymatic breakdown, extending its half-life and increasing its receptor affinity. It acts as an agonist at the MC1R, MC3R, MC4R, and MC5R receptors.25 Activation of MC1R in epidermal melanocytes drives tyrosinase transcription, promoting eumelanin synthesis and skin darkening. Additionally, the peptide crosses the blood-brain barrier to bind to hypothalamic MC4R receptors, stimulating dopaminergic pathways to induce sexual arousal and suppress appetite.
Scientific and Clinical Effects
Subcutaneous Melanotan II administration induces rapid, UV-independent skin tanning. Clinical studies have shown that it effectively stimulates erectile function in men with psychogenic and organic erectile dysfunction, and increases sexual desire in women, though common side effects include nausea, facial flushing, spontaneous yawning, and the darkening of existing moles.
