Melanotan II

experimental

Also 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). It acts as a non-selective agonist at melanocortin receptors, primarily MC1R (expressed on melanocytes) and MC4R (expressed in the hypothalamus). Activation of MC1R stimulates tyrosinase activity and eumelanin production, leading to increased skin pigmentation independent of UV exposure. Concurrent MC4R agonism modulates central pathways involved in energy homeostasis and sexual behavior, notably increasing libido and inducing penile erections in preclinical models. **Key Research Findings** Preclinical studies demonstrate that MT-II induces dose-dependent skin darkening in animal models and humans, with effects persisting for weeks after discontinuation. A 2000 phase I/II trial (Dorr et al., *J Invest Dermatol*) reported significant melanogenesis in fair-skinned individuals, alongside adverse effects including nausea, facial flushing, and spontaneous erections. Subsequent research confirmed MC4R-mediated erectogenic properties, with a 2004 study (Wessells et al., *J Urol*) showing increased sexual desire in men with erectile dysfunction. However, MT-II’s lack of receptor selectivity limits its therapeutic utility, as off-target activation of MC3R and MC5R may contribute to dysregulated appetite and sebaceous gland activity. **Clinical Relevance** Despite experimental status, MT-II has been investigated for UV-protective tanning in photosensitive disorders (e.g., erythropoietic protoporphyria) and as a treatment for hypoactive sexual desire disorder. No regulatory approvals exist; safety concerns include potential melanocytic proliferation, dysplastic nevus transformation, and unpredictable cardiovascular effects from MC4R activation. Current research focuses on developing selective MC1R agonists (e.g., afamelanotide) to separate tanning from sexual side effects. For research purposes only — not medical advice.

Key data

Category
Sexual Health
Molecular weight
1024.2 g/mol
Molecular formula
C50H69N15O9
CAS number
121062-08-6
Administration
subcutaneous
Research status
experimental
References
194
Tags
melanocortin, tanning, libido

Research & studies

Barbie drug identification: Not a child's play
Journal of forensic sciences · 2024 · PubMed
5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II
Chemistry (Weinheim an der Bergstrasse, Germany) · 2024 · PubMed

Efficient condensation of 5-hydroxypyrroloindoline with cysteine-thiol or tryptophan-indole forms tryptathionine or 2,2'-bis-indole staples.; Protecting groups enable chemoselective stapling in α-MSH-based peptides.; Both staple types yield nanomolar K_i values, with one achieving sub-nanomolar affinity.

Melanotan-II reverses memory impairment induced by a short-term HF diet
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023 · PubMed

Short-term HF diet (3 weeks) impaired recognition memory in zebrafish.; HF diet elevated anxiety and reduced exploratory behavior.; MT-II treatment reversed all HF diet-induced behavioral abnormalities.; This is the first study showing MT-II can reverse diet-induced neurobehavioral changes.

Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food
Neuropeptides · 2022 · PubMed
CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists
Journal of medicinal chemistry · 2022 · PubMed
Melanotan II User Experience: A Qualitative Study of Online Discussion Forums
Dermatology (Basel, Switzerland) · 2021 · PubMed
Combining MALDI mass spectrometry imaging and droplet-base surface sampling analysis for tissue distribution, metabolite profiling, and relative quantification of cyclic peptide melanotan II
Analytica chimica acta · 2020 · PubMed
Melanotan II: a possible cause of renal infarction: review of the literature and case report
CEN case reports · 2020 · PubMed

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). It acts as a non-selective agonist at melanocortin receptors, primarily MC1R (expressed on melanocytes) and MC4R (expressed in the hypothalamus). Activation of MC1R stimulates tyrosinase a

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).

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