Melanotan II

Q: What is Melanotan II?

Melanotan II is a synthetic analog of alpha-MSH studied for its effects on pigmentation pathways and melanocortin receptor signaling in research settings.

Q: How is Melanotan II typically evaluated in studies?

Melanotan II is evaluated using in vitro models, ex vivo skin systems, and experimental animals to examine pigmentation, receptor activity, and downstream signaling markers.

Daniel Attalla
Nov 2
4 min read

Updated: Nov 13

Overview

Melanotan II (MT‑II) is a synthetic cyclic heptapeptide analog of α‑melanocyte‑stimulating hormone (α‑MSH). It activates melanocortin receptors, particularly MC1R on melanocytes, to increase eumelanin synthesis. Interest has centered on pigmentation enhancement, photobiology/photoprotection, neuromodulatory effects (including appetite and sexual arousal pathways), and broad melanocortin signaling.

Mechanism of Action (Research Context)

By agonizing MC1R on melanocytes, MT‑II up‑regulates eumelanin (brown/black melanin) production and can augment the tanning response; eumelanin is associated with improved photoprotection compared with pheomelanin. MT‑II and related analogs can interact with other melanocortin receptors (e.g., MC3/4/5) expressed in the CNS and peripheral tissues, which is consistent with reported effects on appetite and sexual function in experimental settings.

Potential Research Benefits (Reported in Literature)

• Pigmentation enhancement and tanning response

Multiple investigations describe increases in eumelanin content and an exaggerated tanning response to UV light. In controlled settings, α‑MSH analogs increased pigmentation without pathologic findings at exposed sites, and effects were synergistic with UV exposure in some protocols.

• Photoprotection / photobiology

Because eumelanin is photoprotective, increased MC1R signaling is mechanistically linked to reduced UV‑induced damage in skin models. Reviews emphasize the central role of the α‑MSH/MC1R axis in photoprotection and support the rationale for studying MT‑II in this context.

• Appetite modulation (research context)

Melanocortin pathways in the hypothalamus regulate energy balance. Reports and commentaries note decreased appetite in some subjects exposed to MT‑II analogs, consistent with central MC3/MC4 receptor activation; magnitude of effect varies by dose and protocol.

• Sexual arousal / libido effects (research context)

Early randomized, placebo‑controlled experiments reported increases in sexual desire and erectile response in male subjects following MT‑II exposure; subsequent pharmacologic development led to bremelanotide for HSDD in premenopausal populations. These observations support ongoing interest in melanocortin‑mediated sexual function pathways.

Potential Reported Side Effects / Adverse Events

Across trials, observational reports, and safety statements, subjects most commonly report transient flushing, nausea, decreased appetite, yawning/somnolence, headache, and GI upset. Erection‑related events have been described in males (including prolonged erections in rare cases). Dermatologic changes such as new or darkening nevi and freckling have been described in surveillance reports; any pigmentary change warrants clinical evaluation. Regulatory advisories also caution about unapproved products and potential serious risks with unsupervised use.

Reported Findings / Key Points

• Photobiology: increased eumelanin and enhanced tanning response in controlled settings.

• Sexual function signals: increased sexual desire metrics in early MT‑II studies; modern development of bremelanotide built on this pathway.

• Appetite: qualitative reports of reduced appetite are consistent with central melanocortin signaling.

• Tolerability: nausea and flushing are the most frequent short‑term effects; severity is dose‑dependent in early studies.

• Safety notes: pigmentary lesion changes have been reported; unregulated products raise additional risk concerns.

Chemical / Physical Information

• Sequence (example): Ac‑Nle‑c[Asp‑His‑D‑Phe‑Arg‑Trp‑Lys]‑NH₂ (cyclic heptapeptide) • Target receptors: primarily MC1R (pigmentation), with activity at MC3/4/5 (CNS/peripheral effects) • General handling (peptide guidance): store lyophilized material at −20 °C, protect from light/moisture; aliquot reconstituted solutions; avoid repeated freeze–thaw.

Notes on Formats Studied

Published protocols have investigated different experimental formats (e.g., subcutaneous administration). Dosing schedules and endpoints vary; interpret results within each study’s design and population.

Regulatory & Compliance Notes

Regulatory agencies have issued advisories regarding unapproved products marketed for tanning or other purposes. Status and legal frameworks differ by jurisdiction; confirm local requirements before any regulated activity.

References (Selection)

• Dorr RT, et al. Effects of a superpotent melanotropic peptide in volunteers. JAMA Dermatology, 2004. • Wessells H, et al. Melanocortin agonists and sexual function; early MT‑II data. • Kingsberg SA, et al. Bremelanotide for HSDD: phase 3 results (2019). • Böhm M, et al. Chronic MC1R signaling: benefits/risks overview (2024). • DermNet NZ: Melanotan II overview and side effects. • TGA advisory on melanotan products (2025). • Reviews on α‑MSH/MC1R and photoprotection (2024).

Disclaimer

This is only intended for research purposes only. None of this is intended for consumption. This is only for educational purposes.

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Selected References

PMID: 16133878 — Melanotan peptides and melanocortin receptor activation

PMID: 12893986 — Melanocortin pathways in pigmentation and photoprotection

PMID: 18573760 — Melanotan II effects on energy balance and neuroendocrine signaling

PMID: 21717461 — Peptide-based modulation of skin pigmentation and UV defense

Frontiers in Endocrinology — Melanocortin system and neuroregulatory mechanisms

Journal of Peptide Science — Melanocortin-derived peptides and physiological activity

Frequently Asked Questions (FAQ)

Q1: What is Melanotan II?A1: Melanotan II is a synthetic analog of α-MSH (alpha-melanocyte-stimulating hormone) studied for its effects on pigmentation pathways and melanocortin receptor signaling in research settings.

Q2: How does Melanotan II work in research models?A2: Melanotan II activates melanocortin receptors—primarily MC1R for pigmentation and MC3R/MC4R for autonomic and behavioral responses—allowing researchers to study a range of signaling pathways.

Q3: Is Melanotan II approved for human use?A3: No. Melanotan II discussed here is a research compound and is not approved for clinical or general consumer use.

Q4: What are researchers studying Melanotan II for?A4: Research explores Melanotan II in pigmentation models, photoprotection studies, melanocortin pathway mapping, and autonomic signaling.

Q5: Does Melanotan II affect tanning or pigmentation?A5: In research models, Melanotan II increases melanogenesis via MC1R activation, influencing melanin production.

Q6: How is Melanotan II typically evaluated in studies?A6: Studies use in vitro models, ex vivo skin systems, and experimental animals to examine pigmentation, receptor activity, and downstream signaling markers.

Q7: Are there known effects or side effects in research settings?A7: Research models sometimes report flushing, appetite changes, or autonomic responses, though findings vary by protocol and dosage.

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