Melanotan II
The melanocortin-receptor analog studied for its effects on pigmentation, libido, and the neuroendocrine melanocortin system.
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What Is Melanotan II?
Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH). Originally developed in the 1980s at the University of Arizona as a potential photoprotective agent — the goal was to stimulate melanin production and reduce skin cancer risk in fair-skinned populations.
Unlike its sibling compound Melanotan I (afamelanotide), which is selective for the melanocortin-1 receptor (MC1R) responsible for melanogenesis, Melanotan II is a broad melanocortin agonist — it activates MC1R, MC3R, MC4R, and MC5R. This broad receptor profile produces the characteristic constellation of effects: tanning (MC1R), libido (MC4R), and appetite suppression (MC3R/MC4R).
Afamelanotide reached clinical use under the brand name Scenesse for erythropoietic protoporphyria. Melanotan II did not — the broader receptor profile, side-effect burden, and safety concerns with unsupervised use have kept it research-only.
History & Discovery
Melanotan II was developed at the University of Arizona in the 1980s by a team led by Mac E. Hadley and Victor J. Hruby. The original therapeutic motivation was photoprotection — Arizona dermatologists were watching skin cancer rates climb in fair-skinned populations, and the team hypothesized that a synthetic α-MSH analog could stimulate eumelanin production and reduce UV damage risk.
The cyclic heptapeptide structure was the result of deliberate medicinal chemistry — α-MSH itself is rapidly degraded by serum peptidases, with a half-life measured in minutes. The disulfide bridge between residues 4 and 10 in MT-II creates a constrained ring that resists proteolysis and confers receptor selectivity at MC1R, MC3R, MC4R, and MC5R.
MT-II's broader profile was originally a bug, not a feature. The team also synthesized a sister compound (NDP-α-MSH, later afamelanotide / Melanotan I) that was more selective for MC1R — the receptor responsible for melanin synthesis without the libido and appetite effects. Afamelanotide became the FDA-approved compound (Scenesse) for erythropoietic protoporphyria; MT-II did not.
MT-II entered the gray-market peptide ecosystem in the 2000s and became one of the most widely used research peptides — driven primarily by interest in its tanning, libido, and appetite-suppressing effects. It has never received FDA approval for any indication.
Mechanism of Action
Melanotan II binds and activates melanocortin receptors — primarily MC1R, MC3R, MC4R, and MC5R. MC1R activation on melanocytes drives the conversion of pheomelanin (red/yellow) to eumelanin (brown/black), producing the visible tanning response without UV exposure.
MC4R activation in the hypothalamus affects sexual function — it is the same pathway exploited by bremelanotide (PT-141), a more selective MC3R/MC4R agonist FDA-approved for hypoactive sexual desire disorder. MC4R activation also influences appetite, which underlies the appetite-suppressing effect Melanotan II users often report.
The cyclic structure of Melanotan II (a disulfide bridge between residues 4 and 10) confers metabolic stability that native α-MSH lacks, extending its biological activity from minutes to hours.
Pharmacokinetics
| Molecular weight | 1,024.18 Da (cyclic heptapeptide) |
| Receptor selectivity | MC1R, MC3R, MC4R, MC5R (broad agonist) |
| Half-life (T½) | Approximately 33 minutes after subcutaneous injection |
| Time to peak | ~30 minutes post-injection |
| Onset of pigmentation | Visible darkening within 7–14 days of consistent dosing |
| Duration of pigment effect | Several weeks after discontinuation as melanin clears |
| Onset of libido / appetite effects | Within hours of single dose |
Research Use Cases
Melanogenesis & UV-Independent Tanning
The original research application — eumelanin production in fair-skinned subjects without UV exposure. Effects are visible within 1–2 weeks of consistent dosing.
Melanocortin Receptor Pharmacology
Used as a research tool to probe the melanocortin system — receptor selectivity, downstream signaling, and tissue-specific effects.
Sexual Function Research
MC4R activation influences sexual desire and erectile function. This pathway led to the development of the more selective bremelanotide (PT-141).
Appetite Modulation Studies
The hypothalamic MC4R pathway is central to appetite regulation. Melanotan II's appetite-suppressant effect has been used to study these circuits.
Photoprotection Research
Increased eumelanin content provides modest UV photoprotection — the original therapeutic hypothesis behind the development program.
Research Dosing Reference
Loading phase (research)
Used to establish the initial pigmentation response. Most subjects see visible tanning by day 10–14.
Maintenance phase
Maintains pigmentation once the initial loading effect has been achieved.
Conservative starter (research)
Recommended for subjects highly sensitive to nausea or flushing. Pigmentation onset is slower.
Stacking & Combinations
Melanotan II + UV Exposure
Not a pharmacological stack, but the standard pairing. Modest sun or UV-bed exposure during the loading phase accelerates eumelanin deposition. Without any UV exposure, baseline pigmentation increase is much slower.
Melanotan II + PT-141 (rare, research only)
Both are melanocortin agonists. Combining is generally avoided because PT-141 is more selective for the MC4R libido pathway already activated by MT-II — the combination compounds nausea and flushing without obvious benefit.
Side Effect Profile
Common / Mild-to-Moderate
- •Nausea (most common, often dose-limiting; usually subsides over the first week)
- •Facial flushing within minutes of injection
- •Decreased appetite
- •Spontaneous erections (in male subjects)
- •Increased libido
- •Darkening of existing moles, freckles, and lentigines
- •Yawning and mild fatigue post-injection
Serious / Less Common
- •Development of new nevi (atypical or otherwise) — has prompted dermatologist concern about long-term use
- •Cardiovascular effects: tachycardia, blood pressure changes
- •Reports of melanoma in long-term unregulated users — causal relationship unproven but warranting concern
- •Rhabdomyolysis (rare; isolated case reports)
- •Posterior leukoencephalopathy (rare; isolated case reports in unsupervised users)
Long-term safety data is essentially nonexistent — no large controlled human trials. Regular full-body skin examinations by a dermatologist are widely recommended for any sustained MT-II use, given the documented effects on existing nevi and the unresolved questions about new lesion formation.
Storage & Reconstitution
- Lyophilized vials are stored refrigerated at 2–8°C. Stable at room temperature for short shipping intervals.
- Reconstitute with bacteriostatic water for injection. For a 10 mg vial, 1 mL is the most common volume — yielding 10 mg/mL, where 100 mcg = 1 unit on a 100-unit insulin syringe.
- Inject the BAC water against the vial wall slowly. Swirl gently — never shake.
- Once reconstituted, store refrigerated. MT-II is reasonably stable for 30+ days at refrigerator temperatures.
- Use a 31G insulin syringe for subcutaneous injection. Rotate sites between abdomen, thigh, and posterior arm.
- Many users inject in the evening to allow nausea to resolve during sleep.
Key Studies & Trial Data
Melanotan II for tanning in fair-skinned subjects
Early human pigmentation trial at the University of Arizona. 28 subjects received MT-II; visible eumelanin-mediated tanning was observed in 27 of 28 within 14 days, establishing the dose-response relationship that informed subsequent research.
Dorr RT, et al. Life Sci. 1996;58(20):1777–1784.
Effect of Melanotan on erectile dysfunction
Single-blind crossover study of MT-II in men with psychogenic erectile dysfunction. Subcutaneous MT-II produced significant improvement in erectile response versus placebo — the finding that ultimately led to development of the more selective bremelanotide (PT-141).
Wessells H, et al. J Urol. 1998;160(2):389–393.
Adverse events from unregulated Melanotan use
Case-series review documenting darkening of nevi, development of new pigmented lesions, and cardiovascular events in users of unregulated Melanotan products. Established the dermatology community's cautionary stance on unsupervised use.
Cardones AR, et al. JAMA Dermatol. 2009;145(9):1058–1059.
Comparisons & Deep Dives
In-depth articles on Peptide Basics that compare Melanotan II to related compounds and expand on its mechanism and use.
Melanotan II vs Melanotan I (Afamelanotide)
Receptor selectivity, clinical history, and why one became a prescription medication while the other did not.
Melanotan II vs PT-141 (Bremelanotide)
Both are melanocortin agonists. PT-141 is more selective for MC3R/MC4R and FDA-approved. MT-II is broader and research-only.
Frequently Asked Questions
Where to Source Research-Grade Melanotan II
Base Peptide
Research-grade Melanotan II (10 mg vial) with batch-specific Certificate of Analysis confirming purity by HPLC and identity by mass spectrometry. Lyophilized powder, requires reconstitution.
Other reputable suppliers known for batch-specific Certificates of Analysis:
Want a deeper, ongoing reference? Peptide Basics maintains a comprehensive resource on Melanotan II alongside calculators, reconstitution guides, and a database of 60+ research peptides.
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