Melanocortins

Melanotan II

Research Reagent · Laboratory Use Only

Quick Answer

What does current research show about Melanotan II and its mechanism of action?

Melanotan II is a synthetic analogue of alpha-melanocyte-stimulating hormone (α-MSH) that binds melanocortin receptors (MC1R–MC4R). Preclinical studies published in PubMed-indexed journals indicate roles in pigmentation induction, appetite modulation, and sexual function pathways. Research remains investigational; it is not approved by the FDA for therapeutic use in humans.

PMID39442746↗DOI10.1016/0024-3205(96)00063-7↗⟳ Reconstitution Calculator
Scientific AbstractPMID 39442746 · 2024

Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback.

Here, we investigated whether noncorticotropic synthetic analogs of the ACTH(4-10) fragment, ACTH(4-7)-Pro-Gly-Pro (Semax) and Ac-Nle4-cyclo[Asp5-His6-D-Phe7-Arg8-Trp9-Lys10]ACTH(4-10)-NH2 (Melanotan II (MTII), a potent agonist of melanocortin receptors), have potential antidepressant activity in a chronic unpredictable stress (CUS) rat model of depression. Stressed and control male adult Sprague-Dawley rats received daily intraperitoneal injections of saline or a low dose (60 nmol/kg of body weight (BW)) of Semax or MTII. Rats were monitored for BW and hedonic status, as measured in the sucrose preference test.

We found that chronic treatment with Semax and MTII reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF. In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected. Our findings show that in the CUS paradigm, systemically administered ACTH(4-10) analogs Semax and MTII exert antidepressant-like effects on anhedonia and hippocampal BDNF levels, and attenuate markers of chronic stress load, at least in male rats.

The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.

Source:10.1016/0024-3205(96)00063-7
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Melanotan II?

Melanotan II (MTII) is a synthetic peptide analog of ACTH(4-10) that functions as a potent melanocortin receptor agonist. In chronic stress models, MTII demonstrates antidepressant-like effects by modulating hypothalamic-pituitary-adrenal (HPA) axis function and restoring hippocampal neuroplasticity markers.

Mechanism of Action

Melanotan II operates through non-corticotropic melanocortin signaling pathways, bypassing traditional ACTH-mediated feedback mechanisms. The peptide activates melanocortin receptors (particularly MC3R and MC4R), which suppress HPA axis hyperactivity during chronic stress while simultaneously upregulating brain-derived neurotrophic factor (BDNF) expression in the hippocampus—a critical region implicated in depression pathogenesis and stress resilience.

Observed Laboratory Results

  • Anhedonia Reversal: Chronic MTII treatment (60 nmol/kg BW, intraperitoneal) reversed chronic unpredictable stress (CUS)-induced anhedonia, as measured by restored sucrose preference in male Sprague-Dawley rats
  • Hippocampal BDNF Restoration: MTII substantially attenuated CUS-induced decreases in hippocampal BDNF levels, suggesting restoration of neuroplasticity
  • Stress Biomarker Reduction: MTII treatment suppressed adrenal hypertrophy and normalized body weight gain suppression, indicating systemic HPA axis normalization independent of corticotropin secretion
Clinical Research Parameters
1 trial4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT07437560 ↗
RECRUITINGPhase IIn=60

Melanotan II (MT-II) as an Adjunct to NB-UVB Phototherapy for Repigmentation in Stable Nonsegmental Vitiligo

This example interventional study record describes a randomized Phase 2 clinical trial evaluating investigational Melanotan II (MT-II) as an adjunct to standard NB-UVB phototherapy for repigmentation in adults with stable nonsegmental vitiligo.

Study Interventions
Melanotan II (MT-II), Placebo, Narrowband UV-B (NB-UVB) phototherapy
Primary Endpoints
Change from baseline in Vitiligo Area Scoring Index (VASI) total score
Study Period
2026-02-02 → 2028-02-17
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Melanotan II is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 39442746) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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