43 amino acids

ExperimentalSexual Health

Melanotan II

Also known as: MT-II, MT2, Melanotan 2, CUV-1647

Molecular weight
1024.18 Da
Formula
C50H69N15O9
CAS
121062-08-6
Routes
4

Melanotan II (MT-II) is a synthetic cyclic lactam analog of alpha-melanocyte-stimulating hormone (α-MSH) developed at the University of Arizona. It is a non-selective melanocortin receptor agonist that activates MC1R (pigmentation), MC3R, MC4R (sexual function), and MC5R, producing a broad spectrum of effects including skin tanning, sexual arousal enhancement, appetite suppression, and fat mobilization. Originally developed as a sunless tanning agent to reduce UV exposure and skin cancer risk, MT-II was found to produce potent pro-sexual effects during clinical trials — a discovery that led to the development of PT-141 (bremelanotide) as a more targeted sexual dysfunction therapy. MT-II remains the parent compound from which PT-141 was derived. Despite never receiving regulatory approval, MT-II has become one of the most widely used unregulated peptides globally, primarily for tanning and sexual enhancement. Its use carries significant safety concerns due to its non-selective receptor activation profile and potential for uncontrolled melanocyte stimulation.

For educational and research purposes only
Last updated:Check the research sources

Section 01

What it's used for

Tanning without UV, early trials

MT-II was first studied for darkening skin without UV exposure. A small early trial in three people saw visible tanning in two. Whether it reduces UV-caused DNA damage is untested in humans, and safety concerns stalled further trials.

HumanLimited data
Clinical wording

MT-II's ability to stimulate melanin production without UV exposure was its original research application. A small phase-I pilot study in three subjects reported visible skin darkening in two of them; whether this effect extends across skin types or reduces UV-induced DNA damage remains theoretical and has not been tested in humans. Concerns about uncontrolled melanocyte stimulation have limited further clinical development.

Erectile function trials in men

In placebo-controlled trials, MT-II improved erections and libido in men with erectile dysfunction. It led researchers to develop PT-141 (bremelanotide), which was tested in women — no published trial of MT-II itself in women exists.

Human
Clinical wording

Double-blind, placebo-controlled clinical trials showed MT-II improved erections in men with both psychogenic and organic erectile dysfunction, including increased libido and enhanced arousal. MT-II was the proof-of-concept compound that led to the development of PT-141 (bremelanotide); it was PT-141, not MT-II, that was subsequently tested for female sexual arousal disorder. No published clinical trial of MT-II itself in women was found.

Appetite research, animal studies

MT-II acts on a brain receptor (MC4R) that controls appetite. In rodent studies, it reduced food intake and body weight, including in diet-induced obesity models. No human trial of MT-II for appetite or weight has been found.

Human
Clinical wording

MC4R-mediated appetite suppression makes MT-II a research tool for studying melanocortin appetite regulation. Animal studies have demonstrated reductions in food intake and body weight in rodent models, including diet-induced obesity and hindbrain leptin-signaling studies; no human clinical trial of MT-II for appetite or weight reduction was found.

Tanning as cancer prevention?

Scientists are researching whether producing melanin with a drug, instead of sun exposure, could protect skin from cancer. Whether MT-II's effect on pigment actually lowers melanoma risk without raising it remains under investigation.

Limited data
Clinical wording

The concept of pharmacological tanning (melanin production without UV) as skin cancer prevention is an active research area. Whether MT-II-induced melanogenesis provides genuine photoprotection without increasing melanoma risk remains under investigation.

Section 02

Mechanism of Action

Mechanism 01

Skin darkening without sunlight

  • It switches on a receptor of the pigment cells sitting in the lowest layer of the skin.
  • A signalling chain then raises a master switch that turns on the pigment-making enzymes.
  • Brown-black pigment builds up, so skin darkens without sun, though sun speeds the process up.
Clinical wording

MC1R Activation (Tanning)

MT-II activates MC1R on melanocytes in the basal layer of the epidermis. MC1R signaling through cAMP/PKA/CREB increases transcription of MITF (microphthalmia-associated transcription factor), which drives expression of melanin synthesis enzymes — tyrosinase, TRP-1, and TRP-2. This produces eumelanin (brown/black pigment) deposition, resulting in skin darkening without UV exposure (though UV exposure accelerates the process).

Mechanism 02

Arousal signals in the brain

  • It also activates two related receptors in the deep brain region that governs basic drives.
  • Those receptors work through dopamine and oxytocin pathways tied to sexual desire and arousal.
  • The effect is described as stronger than PT-141 because more receptor types are engaged.
Clinical wording

MC3R/MC4R Activation (Sexual Function)

Like PT-141, MT-II activates hypothalamic MC3R and MC4R, stimulating sexual desire and arousal through dopaminergic and oxytocinergic pathways. The sexual effects are generally more pronounced than with PT-141 due to MT-II's broader receptor activation profile.

Mechanism 03

Turning hunger signals down

  • In the brain's appetite centre it strengthens the nerve cells that signal fullness.
  • At the same time it quiets the opposing nerve cells that drive hunger.
  • Reports describe a marked drop in food intake while the compound is used.
Clinical wording

MC4R Activation (Appetite Suppression)

MC4R activation in the hypothalamic arcuate nucleus stimulates POMC/α-MSH signaling and suppresses NPY/AgRP neurons, producing significant appetite reduction. This anorexigenic effect can cause notable food intake reduction during MT-II use.

Mechanism 04

Nerve signals that release stored fat

  • Activating the brain receptor increases nerve traffic from the stress branch to fat tissue.
  • Those nerves hit a receptor on fat cells that makes them release stored fat.
  • This is described as contributing to the fat loss observed with the compound.
Clinical wording

MC4R-Mediated Lipolysis

Hypothalamic MC4R activation enhances sympathetic nervous system outflow to adipose tissue, promoting lipolysis through β3-adrenergic receptor stimulation. This contributes to fat loss effects observed with MT-II use.

Section 03

Biological Pathways

  1. MC1R/cAMP/CREB/MITF MelanogenesisMT-II activates MC1R on basal-layer melanocytes; cAMP/PKA/CREB signaling raises MITF transcription, driving tyrosinase, TRP-1, and TRP-2 expression that deposits eumelanin and darkens skin without UV exposure.
  2. MC3R/MC4R Sexual FunctionLike PT-141, MT-II activates hypothalamic MC3R and MC4R, stimulating desire and arousal through dopaminergic and oxytocinergic pathways; effects run stronger than PT-141's due to broader receptor activation.
  3. MC4R Appetite SuppressionMC4R activation in the hypothalamic arcuate nucleus stimulates POMC/alpha-MSH signaling and suppresses NPY/AgRP neurons, producing an anorexigenic effect that can cause notable food intake reduction during use.
  4. MC4R-Mediated LipolysisHypothalamic MC4R activation raises sympathetic outflow to adipose tissue, promoting lipolysis via beta-3-adrenergic receptor stimulation and contributing to the fat-loss effects reported alongside MT-II use.
  5. p53-Mediated DNA RepairMC1R activation can enhance p53-mediated nucleotide excision repair in melanocytes, but sustained proliferation without UV exposure may also mask damage, potentially raising melanoma risk in certain contexts.

Section 04

Dosage Information

Amino acid sequence
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
Ranges reported in experimental work
Route / systemContextRange studiedLimitation
Subcutaneous — tanning, stepped-up doses1996 pilot phase-1 study, 3 male volunteers0.01 mg/kg a day raised in 0.005 mg/kg steps to 0.025–0.03 mg/kg — about 1.8–2.7 mg for a 70–90 kg adult; Monday to Friday, two weeksThree men, and nothing measured but skin colour. 0.03 mg/kg caused drowsiness and fatigue, so 0.025 mg/kg was picked for a next study that never set a dose.
Subcutaneous — erectile dysfunction1998 blinded trial, 10 men, ED with no physical causeOne 0.025 mg/kg dose — about 1.8–2.3 mg for a 70–90 kg adult; erections over 80% firmness lasted 38 minutes against 3 on placeboTen men, one dose each, measured by a rigidity monitor in 1998. Development moved on to bremelanotide, and no repeat-dose trial was ever finished.
Subcutaneous — self-administrationCirculating practice, outside any trial250–500 µg daily for one to two weeks, then about 500 µg once or twice weekly — roughly 3–7 µg/kg for a 70–90 kg adult; vials are 10 mgPractice, not a finding: below the 0.025 mg/kg ever studied, approved by no regulator, contents unverified, months of repeat injections never studied.
Subcutaneous — documented overdosePoison-centre case report, 2012One 6 mg injection — six times the seller's starting dose. A muscle-breakdown marker rose from 1760 to 17,773 IU/L in 12 hoursA single case, but it sets the scale: six times a starting dose put a 39-year-old man in intensive care for three days with muscle and kidney damage.
Dosage calculatorMass · concentration · volume · U-100

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Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Section 05

Protocols

No protocols featuring this peptide yet. Browse All Protocols

Section 06

Stability & Storage

  1. Lyophilised powder

    Melanotan II is supplied as a white lyophilised powder kept at -20°C for long-term stability (18-24 months) or at 2-8°C for up to 6 months. Its cyclic structure gives it more protease resistance than linear melanocortin analogues.

  2. After reconstitution

    Reconstituted with bacteriostatic water, the solution is stored at 2-8°C and used within 21-28 days. It is photosensitive, so prolonged light exposure is avoided since it can oxidise tryptophan residues; the solution should stay clear and colourless, as discolouration signals degradation.

Section 07

Side Effects & Precautions

Melanotan II's side effects trace to its broad activation of melanocortin receptors: common acute reactions after injection, changes in existing moles, and a melanoma risk that case reports have not resolved.

  1. Acute reactions after injection

    • Nausea, the most common acute effect, affects 50-70% of users and starts 30-60 minutes after injection; it is dose-dependent and often lessens with repeated use.
    • Facial flushing and a feeling of warmth occur in most users for 30-60 minutes after injection, linked to melanocortin-mediated vasodilation (widening of blood vessels).
  2. Spontaneous erections

    Unwanted erections are commonly reported in males, sometimes lasting 2-4 hours, linked to MC3R/MC4R-mediated sexual arousal pathways (melanocortin receptors involved in arousal). In rare cases, priapism (a prolonged, painful erection) has been reported.

  3. Appetite loss and fatigue

    • Appetite and food intake drop through MC4R-mediated anorexia (appetite loss from this melanocortin receptor); the effect is dose-dependent and continues during use.
    • Many users report lethargy and sleepiness, likely linked to central melanocortin effects on arousal circuits (brain pathways controlling wakefulness).
  4. Skin and mole changes

    • Melanotan II stimulates all melanocytes, including those in moles (nevi): existing moles may darken, enlarge, or change appearance, and new moles may also appear.
    • Tanning can be patchy or uneven, with some areas (face, arms) darkening more than others; freckles may darken dramatically, and darkening of genital skin is common.
    • Because Melanotan II already changes the look of moles, a new melanoma developing within one may be harder to notice.
  5. Potential melanoma risk

    • This is the most serious safety concern: Melanotan II stimulates melanocyte proliferation without the DNA-damage checkpoints normally triggered by UV exposure.
    • This may promote melanoma, especially in people with pre-existing dysplastic nevi (abnormal moles) or other melanoma risk factors.
    • Several case reports have linked Melanotan II use to melanoma, though causation has not been definitively established.

Section 08

Regulatory Status

Melanotan II is not approved by any national medicines regulator in the world.

No jurisdiction has authorised it as a drug for tanning, libido, or any other indication, and it is sold only through unregulated research-chemical channels.

  1. FDA / United States

    Not approved; sold illegally as a drug

    The FDA treats MT-II sold online as an unapproved new drug and has issued warning letters to sellers, including one in 2020 over melanopharmacy.com's marketing of injectable MT-II; no manufacturer has ever filed an approved application.

  2. MHRA / United Kingdom

    Not licensed; illegal to sell

    No Melanotan product holds a UK marketing authorisation. The MHRA has logged dozens of suspected adverse-event reports and worked with internet providers to take down over 100 websites illegally trading the substance.

  3. TGA / Australia

    Prescription-only; no approved product

    No Melanotan formulation appears on the Australian Register of Therapeutic Goods. Supplying it without a doctor's prescription is unlawful, and the TGA has issued infringement notices against illegal sellers.

  4. WADA

    Prohibited under category S0

    Melanotan II is a non-approved substance under WADA's catch-all S0 category, meaning it is banned for competing athletes at all times, in and out of competition, with no therapeutic-use exemption available.

A "research use only" label is a legal fiction, not a safety guarantee: it says nothing about purity, dose, or sterility. Regulatory status differs by jurisdiction and can change — check the current position of your own regulator before relying on any of this.

Section 09

Research Studies

  1. [1]Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical studyDorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME · Life Sciences · 1996
  2. [2]Melanocortin peptide therapeutics: historical milestones, clinical studies and commercializationHadley ME, Dorr RT · Peptides · 2006
  3. [3]Melanocortin 1 Receptor: Structure, Function, and RegulationWolf Horrell EM, Boulanger MC, D'Orazio JA · Frontiers in Genetics · 2016
  4. [4]Melanocortin-1 receptor structure and functional regulationGarcía-Borrón JC, Sánchez-Laorden BL, Jiménez-Cervantes C · Pigment Cell Research · 2005
  5. [5]Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover studyWessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N · The Journal of Urology · 1998
  6. [6]Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan IIWessells H, Levine N, Hadley ME, Dorr R, Hruby V · International Journal of Impotence Research · 2000
  7. [7]A role for the melanocortin 4 receptor in sexual functionVan der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, et al. · Proceedings of the National Academy of Sciences · 2002
  8. [8]Role of melanocortinergic neurons in feeding and the agouti obesity syndromeFan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD · Nature · 1997
  9. [9]The central melanocortin system directly controls peripheral lipid metabolismNogueiras R, Wiedmer P, Perez-Tilve D, Veyrat-Durebex C, Keogh JM, Sutton GM, et al. · Journal of Clinical Investigation · 2007
  10. [10]Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a reviewHabbema L, Halk AB, Neumann M, Bergman W · International Journal of Dermatology · 2017

Section 10

Frequently Asked Questions

No regulator has approved it, and the FDA, EMA, TGA, and MHRA have all issued public warnings against its use. Its trials were tiny — three men for tanning, ten men for one erectile-dysfunction dose — and a documented 2012 overdose case (a single 6 mg injection, six times a typical starting dose) put a 39-year-old man in intensive care for three days with a muscle-breakdown marker that rose tenfold in 12 hours.

This is the most serious concern attached to it. Melanotan II stimulates melanocyte growth without the DNA-damage checkpoints that UV-triggered tanning involves, and several case reports link its use to melanoma, though causation hasn't been definitively established. Separately, it darkens and changes existing moles, which can mask the early signs of melanoma developing underneath — dermatological monitoring is strongly advised for exactly this reason.

Unwanted spontaneous erections are commonly reported in men using it, sometimes lasting two to four hours, from its action on sexual-arousal receptors in the brain. In rare cases this has progressed to priapism — a prolonged, painful erection that requires emergency medical treatment.

Nausea affects an estimated 50 to 70% of users, typically 30 to 60 minutes after injection and easing with continued use. Facial flushing and warmth occur in most users for 30 to 60 minutes, and fatigue or drowsiness is widely reported. Appetite suppression is dose-dependent and persists throughout use.

Trials used stepped doses up to about 0.03 mg/kg a day for tanning (three men) or a single 0.025 mg/kg dose for erectile dysfunction (ten men). The 250 to 500 µg daily doses that circulate outside trials sit below even those studied doses, come from unverified vials, and have never been tested for repeated use over months — the overdose case above shows what happens well above that range, not within it.

In principle, yes — it drives melanin production through the same MC1R pathway regardless of UV light, though UV exposure speeds the process along. The only direct human evidence is a three-person pilot study where two of three subjects visibly darkened; whether this provides real UV protection or reduces UV-related DNA damage in people has not been tested and remains theoretical.

The lyophilized powder keeps 18 to 24 months at −20°C or up to 6 months at 2–8°C. Once reconstituted, it should be kept at 2–8°C, used within 21 to 28 days, and protected from light — it's sensitive to light-driven oxidation, and any discoloration of a normally clear solution signals it has degraded.