Melanotan II
experimentalAlso known as: MT-2, MT-II
**Mechanism of Action** Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH) that acts as a non-selective melanocortin receptor agonist. It binds with high affinity to melanocortin receptors MC1R (expressed on melanocytes) and MC4R (expressed in the hypothalamus and limbic system). Activation of MC1R stimulates tyrosinase activity and eumelanin synthesis, leading to increased skin pigmentation independent of UV exposure. Concurrent MC4R activation modulates central pathways involved in appetite regulation and sexual behavior, notably increasing libido and inducing penile erections in males. **Key Research Findings** Preclinical and early-phase human studies demonstrate that subcutaneous administration of MT-II induces dose-dependent skin darkening within days, with effects persisting for weeks. A randomized controlled trial (Dorr et al., 2004) reported significant tanning in 80% of subjects, alongside increased sexual desire and spontaneous erections. However, side effects include nausea, facial flushing, and spontaneous erections (priapism risk). Long-term safety data are lacking, and concerns regarding potential melanocyte proliferation and melanoma risk remain unresolved. Animal studies also indicate MC4R-mediated effects on feeding behavior, though weight loss outcomes in humans are inconsistent. **Clinical Relevance** MT-II remains an experimental compound with no FDA approval for any indication. Its unregulated use for cosmetic tanning and off-label sexual enhancement poses risks, including unmonitored dosing, contamination, and unknown long-term carcinogenic potential. The compound’s dual melanogenic and libido-enhancing effects have spurred interest in developing selective MC1R agonists for photoprotection, but MT-II itself is not recommended for clinical use outside controlled research settings. For research purposes only — not medical advice.
Key data
C50H69N15O9Research & studies
Melanotan II has a molecular weight of 1024 Da, exceeding typical mass spectrometer limits of 1000 Da.; The peptide is multi-charged, which is unusual for common drugs of abuse.; No UV spectrum match was found in the library initially, complicating HPLC-DAD identification.; Reference standard confirmed the drug with 30% purity, and it is unapproved due to safety concerns.
5-Hydroxypyrroloindoline condenses with cysteine-thiol or tryptophan-indole to form tryptathionine or 2,2'-bis-indole staples.; Protecting groups enable chemoselective stapling in α-MSH-based peptides.; Both staple types yield peptides with nanomolar Ki values, including one sub-nanomolar Ki.
Short-term HF diet (3 weeks) impaired recognition memory in zebrafish.; HF diet elevated anxiety levels and reduced exploratory behavior.; MT-II treatment reversed all HF diet-induced behavioral abnormalities.; This is the first study to show MT-II reverses diet-induced memory and emotional changes.
Newly designed peptides showed binding affinities ranging from low nanomolar to sub-micromolar for hMCRs.; Compound 5 demonstrated remarkable functional selectivity toward hMC1R compared to parent MT-II.; Enhanced sampling molecular dynamics simulations revealed how cyclization strategy influences peptide conformation and hMC1R affinity.; A model of peptide 5/hMC1R complex was built using the recent cryogenic electron microscopy receptor structure.
Motivations for MT II use included pursuit of tanned appearance for sun holidays and fitness competitions.; Misinformation and unregulated product use were common themes in forum discussions.; Side effects and risks included pigmented skin lesions, infectious disease transmission, and polypharmacy.; Concerning practices involved sunbed use and potentially contaminated products.
MALDI-MSI mapped the detailed molecular distribution of melanotan II and its metabolites in tissue.; LMJ-SSP-LC-HRMS enabled rapid profiling and structural identification of the drug and its metabolites.; Using both techniques in parallel yielded a more comprehensive dataset than either alone.; The combined approach supports evaluation of peptide therapeutic in vivo fate for drug discovery.
Frequently asked questions
What is Melanotan II?
**Mechanism of Action** Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH) that acts as a non-selective melanocortin receptor agonist. It binds with high affinity to melanocortin receptors MC1R (expressed on melanocytes) and MC4R (expressed in the hypothalamus and
How does Melanotan II work?
Non-selective melanocortin receptor agonist that stimulates melanogenesis (tanning) and increases libido via MC1R/MC4R.
What is the research status of Melanotan II?
Melanotan II is currently classified as experimental, with 194 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Melanotan II?
Melanotan II has a molecular weight of approximately 1024.2 g/mol (formula C50H69N15O9).
Related peptides
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Selective MC1R agonist approved (Scenesse) to prevent phototoxicity in erythropoietic protoporphyria by stimulating eumelanin.
Melanocortin MC4R agonist approved for hypoactive sexual desire disorder; acts centrally to increase sexual arousal.
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