Melanotan 2 10 mg

Melanotan 2 (MT-II) is a synthetic cyclic heptapeptide derived from residues 4 to 10 of alpha-melanocyte-stimulating hormone (alpha-MSH). It was designed at the University of Arizona and first reported by Al-Obeidi, Castrucci, Hadley and Hruby in the Journal of Medicinal Chemistry in 1989. The molecular formula is C50H69N15O9, the molecular weight of the free base is 1024.2 g/mol, and the CAS registry number is 121062-08-6.

Three deliberate changes separate MT-II from the native hormone fragment. Methionine at position 4 is replaced by norleucine, removing the oxidation-labile thioether side chain. Phenylalanine at position 7 is inverted to the D-configuration. A side-chain-to-side-chain lactam bridge is then formed between the side-chain carboxyl of Asp5 and the epsilon-amino group of Lys10, closing the linear fragment into a macrocycle. The computed IUPAC name for the structure describes a hexaazacyclotricosane ring, confirming the 23-membered lactam, and the CAS index name records the same closure as a cyclic (2-7) peptide. Al-Obeidi and colleagues reported that ring size mattered: the 23- and 24-membered ring analogues showed prolonged residual activity in both of their skin bioassays, while the 20-, 21- and 22-membered variants did not.

The peptide terminates in a C-terminal carboxamide. This is the single structural feature that distinguishes it from bremelanotide (PT-141), which carries the same cyclised backbone with a free C-terminal acid; the two differ by one formula unit, C50H69N15O9 against C50H68N14O10. MT-II is normally produced by solid-phase synthesis and supplied as a lyophilised acetate salt. A preparative solution-phase route was published by Ryakhovsky and co-workers in the Beilstein Journal of Organic Chemistry in 2008, assembling the hexapeptide by a [(2+2)+1+1] scheme, closing the lactam by carbodiimide-mediated lactamization between the epsilon-amino group of lysine and the side-chain carboxyl of aspartic acid, and finishing by appending N-acetylnorleucine; that route ran to 12 steps for a 2.6% overall yield, affording peptide of greater than 90% purity without preparative chromatography.

The compound entered the literature as a designed pharmacological probe. In the 1989 design paper, seven cyclic peptides were prepared and bioassayed in standard frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. Against alpha-MSH set at a relative potency of 1, Al-Obeidi et al. recorded a relative potency of 90 in the lizard skin assay for Ac-[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH4-10-NH2, the analogue later called MT-II, and noted that similar results were obtained in the frog assay but that the analogues were much less potent there. Weirath and Haskell-Luevano, reviewing melanocortin tool compounds in ACS Pharmacology and Translational Science in 2024, place MT-II alongside NDP-MSH and SHU9119 as reference ligands used to validate stably expressing melanocortin receptor cell lines and as core ligands in assessing cryo-EM structures of active and inactive receptor complexes. They describe the melanocortin receptors as five subtypes that, apart from the melanocortin-2 receptor, are stimulated by a shared set of endogenous agonists.

Two small human studies from the 1990s account for most of the clinical record. Dorr et al. (Life Sciences, 1996) ran a single-blind, alternating-day, placebo-controlled pilot phase-I study in three healthy male volunteers, with subcutaneous injections of MT-II or saline given daily from Monday to Friday for two consecutive weeks. Two of the three subjects showed increased pigmentation of the face, upper body and buttock one week after dosing ended, as measured by quantitative reflectance and by visual perception. At the highest level reached, one of two subjects recorded Grade II somnolence and fatigue on WHO standards, and mild nausea not requiring antiemetic treatment was reported at most levels. A stretching and yawning complex was recorded and appeared to the investigators to correlate with the onset of spontaneous penile erections.

Wessells et al. (Journal of Urology, 1998) followed with a double-blind, placebo-controlled crossover study in ten men with erectile dysfunction of no known organic cause, comparing MT-II against a vehicle placebo using real-time RigiScan monitoring, with presence, duration and rigidity recorded over a six-hour period. Clinically apparent erections developed in 8 of 10 men. Mean duration of tip rigidity greater than 80% was 38.0 minutes with MT-II against 3.0 minutes with placebo (p = 0.0045). Transient side effects of nausea, stretching and yawning, and decreased appetite were reported more frequently after MT-II than after placebo, but none required treatment. Hadley and Dorr later recorded in Peptides (2006) that MT-II had been patented and tested clinically, and that a new MT-II analogue, PT-141, had completed initial phase I/II trials and was scheduled to enter phase III.

Beyond those trials the compound appears mainly as an experimental probe in work indexed under melanocortin signalling, covering feeding and energy balance, thermogenesis, insulin sensitivity, penile erection and analytical pharmacokinetics. A PubMed search run on 26 July 2026 for melanotan II in the title or abstract returns 194 indexed records, of which 55 carry the term in the title. Habbema, Halk, Neumann and Bergman (International Journal of Dermatology, 2017) reviewed the case-report literature: it associates unregulated use of melanotan I and II with cutaneous complications, particularly melanocytic changes in existing moles and newly emerging dysplastic naevi, and identifies four case reports describing melanomas emerging from existing moles during or shortly after use. The authors state that conclusive evidence linking these phenomena is lacking, and note that afamelanotide is the only alpha-MSH analogue approved for use, in a limited number of medical indications. Individual case reports beyond that review describe systemic toxicity with rhabdomyolysis, in which creatine phosphokinase rose to 17,773 IU/L twelve hours after presentation (Nelson, Bryant and Aks, Clinical Toxicology, 2012), and a case of renal infarction (Peters et al., CEN Case Reports, 2020). Case reports establish association, not cause.

One strand of the literature is directly relevant to material quality. Breindahl et al. (Drug Testing and Analysis, 2015) developed and validated LC-UV and LC-MS/MS methods, then applied them to melanotan II vials purchased from three online shops. Every shop claimed its vials contained 10 mg; measured content ranged from 4.32 to 8.84 mg. Vials from two of the three shops carried unknown impurities of 4.1% to 5.9%, while impurities from the third shop fell below the quantification limit. Mestria et al. (Drug Testing and Analysis, 2021) applied Orbitrap LC-HRMS to eight unknown samples confiscated by police, characterising melanotan II and bremelanotide without reference standards. Both papers describe the same underlying problem: for this compound, the label is not the assay, and the only meaningful evidence of what a given vial contains is an analysis from an independent laboratory.