Melanotan II
Skin, Hair & AestheticsPreclinicalMelanotan-II (MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH) engineered in the late 1980s by researchers at the University of Arizona, most prominently Mac Hadley and Victor Hruby, who were searching for a way to stimulate skin pigmentation pharmacologically as a potential skin-cancer prophylactic. The parent hormone α-MSH is a 13-amino-acid peptide cleaved from proopiomelanocortin (POMC) that binds to melanocortin receptors (MC1R through MC5R) scattered across skin, brain, adrenal, and adipose tissue.
Overview
At A Glance
Melanotan-II works by binding to and activating all four G-protein-coupled melanocortin receptors expressed in mammalian tissue (MC1R, MC3R, MC4R, MC5R — MC2R responds only to ACTH), with particularly high affinity at MC1R, MC3R, and MC4R. Melanocortin receptors are coupled prima…
Mechanism of Action
Melanotan-II works by binding to and activating all four G-protein-coupled melanocortin receptors expressed in mammalian tissue (MC1R, MC3R, MC4R, MC5R — MC2R responds only to ACTH), with particularly high affinity at MC1R, MC3R, and MC4R. Melanocortin receptors are coupled primarily to Gαs, so MT-II binding increases adenylyl cyclase activity, raises intracellular cAMP, and activates protein kinase A (PKA) and the cAMP-response element-binding protein (CREB) transcription factor. The downstream effects depend on which tissue expresses the receptor:
MC1R — Melanocytes (Skin Pigmentation): MC1R is the dominant receptor on cutaneous and follicular melanocytes. α-MSH and MT-II binding at MC1R drives cAMP-PKA-CREB signaling that upregulates microphthalmia-associated transcription factor (MITF), the master regulator of melanocyte biology. MITF in turn upregulates tyrosinase, tyrosinase-related protein 1 (TRP-1), and dopachrome tautomerase (DCT/TRP-2) — the three enzymes responsible for converting tyrosine into eumelanin, the darker, photoprotective melanin pigment. MT-II also shifts the eumelanin:pheomelanin ratio toward eumelanin (which is more photoprotective than pheomelanin), explaining why even Fitzpatrick type I-II users who normally make predominantly pheomelanin can develop deep brown tans on MT-II. Pigmentation typically appears within 10-14 days of starting injections, driven by existing melanocytes darkening and new melanin deposition into keratinocytes during normal epidermal turnover (Abdel-Malek et al., 2001).
MC4R — Hypothalamus (Appetite, Sexual Function): MC4R is densely expressed in the paraventricular and ventromedial hypothalamic nuclei. Activation produces dose-dependent appetite suppression — users frequently report 20-40% reductions in food intake during active dosing phases, which is why some off-label users pursue MT-II for weight loss alongside tanning. MC4R in spinal cord and brainstem sexual-response circuits drives central arousal signaling, generating spontaneous erections in men and increased genital engorgement and subjective desire in women (the same mechanism by which PT-141 earned its Vyleesi approval). MC4R signaling is also coupled to blood pressure regulation and sympathetic outflow, which is why MT-II and PT-141 both produce transient blood pressure elevations — typically 5-10 mmHg systolic in the hours after injection (Van der Ploeg et al., 2002).
MC3R — Hypothalamus and Peripheral Tissues (Energy Balance): MC3R contributes to energy homeostasis and fat oxidation, though its role is less well-characterized than MC4R. Activation appears to promote lipolysis and modest fat-mass reduction independent of appetite effects.
MC5R — Sebaceous Glands, Immune Cells: MC5R stimulation on sebaceous glands drives exocrine sebum production, which is why some MT-II users experience oilier skin and acne flares during dosing. MC5R also has immunomodulatory functions on T cells and macrophages whose physiological relevance in MT-II users is unclear.
Because MT-II binds all four receptors, the side-effect profile is an unavoidable package deal: you cannot get MT-II tanning without also accepting MC4R-mediated nausea, appetite suppression, sexual activation, and blood pressure elevation, plus MC5R-mediated seborrhea. This is the fundamental trade-off that motivated the development of receptor-selective successors — PT-141 for MC4R-only and afamelanotide for MC1R-only.
Pharmacokinetically, MT-II administered subcutaneously reaches peak plasma concentrations within 1-2 hours. The cyclic lactam-bridged structure confers resistance to peptidase degradation, giving MT-II a half-life of roughly 30-60 minutes — far longer than native α-MSH but much shorter than conventional pharmaceuticals. Subjective effects (tanning drive, appetite suppression, sexual side effects) typically last 4-8 hours after injection. Because the tanning response is cumulative (melanin deposition builds over weeks), users typically dose daily or every-other-day rather than waiting for continuous plasma coverage.
Overview
Melanotan-II (MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH) engineered in the late 1980s by researchers at the University of Arizona, most prominently Mac Hadley and Victor Hruby, who were searching for a way to stimulate skin pigmentation pharmacologically as a potential skin-cancer prophylactic. The parent hormone α-MSH is a 13-amino-acid peptide cleaved from proopiomelanocortin (POMC) that binds to melanocortin receptors (MC1R through MC5R) scattered across skin, brain, adrenal, and adipose tissue. Native α-MSH has a plasma half-life measured in minutes and is rapidly degraded by peptidases, so Hruby's team cyclized the molecule with a lactam bridge (between Asp5 and Lys10), substituted D-phenylalanine at position 7, and produced a non-selective melanocortin agonist with roughly 1,000-fold greater potency than α-MSH at MC1R and dramatically extended half-life. The resulting compound, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, was patented and licensed, with a truncated MC4R-selective derivative (bremelanotide, PT-141) eventually spinning off to become the FDA-approved HSDD drug Vyleesi in 2019 (Hadley & Dorr, 2006).
MT-II itself has never been approved as a pharmaceutical in any country. Its entry into the human world happened through grey-market channels: bodybuilding forums and online peptide vendors in the early 2000s began selling reconstituted MT-II as an injectable "tanning peptide," and the drug achieved cult status among fair-skinned users who wanted deep tans without UV exposure, people seeking MT-II's appetite-suppressing and libido-improving side effects, and a smaller population with genuine photosensitivity disorders who had exhausted approved therapies. All three use cases rely on MT-II's pan-agonism at melanocortin receptors: MC1R drives melanogenesis in skin melanocytes (tanning), MC4R in the hypothalamus suppresses food intake and drives sexual arousal, and MC3R contributes to energy-balance effects. The Australian Therapeutic Goods Administration, UK MHRA, and US FDA have all issued warnings about MT-II products, citing unknown long-term safety, contamination risk from underground synthesis, and case reports of dysplastic nevi changes following MT-II use (Langan et al., 2010, Cardones & Grichnik, 2009).
MT-II differs meaningfully from its FDA-approved cousin PT-141 (Bremelanotide). PT-141 is a linear 7-amino-acid derivative designed for MC4R selectivity and sexual-function indications — it produces minimal pigmentation and is approved for on-demand use. MT-II by contrast is cyclic, hits all five melanocortin receptors, and generates the tanning effect precisely because it engages MC1R that PT-141 largely spares. Users interested exclusively in libido/erectile effects with less pigmentation usually prefer PT-141; users specifically seeking UV-mimetic tanning (especially those with Fitzpatrick skin types I-II who burn easily) gravitate to MT-II. A separate FDA-approved MC1R-selective peptide called afamelanotide (Scenesse, Clinuvel Pharmaceuticals) received approval in 2019 specifically for erythropoietic protoporphyria patients — it is delivered as a subcutaneous implant and provides months of MC1R activation without the sexual or appetite side effects of MT-II, though at significant cost and with limited regulatory indications (Kim & Jo, 2015).
This entry is for educational purposes only. Melanotan-II is not approved for human use in any jurisdiction, and purchased product quality varies wildly — independent testing of online peptide samples has found significant variation in peptide content, purity, and endotoxin levels. Users considering MT-II should be aware that the drug amplifies the melanogenic response to UV radiation, which means subsequent sun exposure produces a deeper tan but may also accelerate accumulation of UV-induced DNA damage; MT-II is not a sunscreen and does not protect against photoaging or skin cancer risk from concurrent UV exposure. Multiple dermatology case reports have documented rapid darkening and architectural changes in pre-existing moles during MT-II courses, sometimes requiring biopsy to exclude melanoma transformation. Anyone with a personal or family history of melanoma, a large number of atypical nevi, or Fitzpatrick skin type I should exercise particular caution, ideally with a dermatologist performing a full-body mole check before and after any MT-II cycle.
Potential Research Fields
Chemical Information
IUPAC Name
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
CAS Number
121062-08-6
Molecular Formula
C50H69N15O9
Molecular Mass
1024.19 g/mol
Dosing & Protocols
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Interactions
Interaction Matrix
Contraindications
Absolute contraindications (do not use):
- Personal history of melanoma (any stage)
- Personal history of any skin cancer in atypical location or at young age
- Family history of melanoma, particularly first-degree relatives or FAMMM syndrome
- Dysplastic nevus syndrome or >50 atypical nevi
- Known BRAF, CDKN2A, or MC1R-loss-of-function mutations
- Fitzpatrick skin type I (always burns, never tans) — highest baseline melanoma risk
- Pregnancy or active attempt to conceive
- Breastfeeding
- Age < 18
- Severe or uncontrolled hypertension (systolic > 160 or diastolic > 100)
- Recent cardiovascular event (MI, stroke, TIA within 6 months)
- Active significant arrhythmia
- Known hypersensitivity to melanocortin peptides
Strong relative contraindications (use only with specialist oversight):
- Controlled hypertension on medication
- Coronary artery disease or significant cardiac risk factors
- History of priapism (from any cause)
- Psychiatric conditions that may be worsened by melanocortin effects (anxiety disorders, mood disorders during active episodes)
- Concurrent PDE5 inhibitor use
- History of rhabdomyolysis
- Immunocompromised state (grey-market product sterility risks are magnified)
- Renal or hepatic dysfunction severe enough to alter peptide clearance
Drug interactions:
- PDE5 inhibitors (sildenafil, tadalafil, vardenafil): Combination produces highest-risk scenario for priapism. Avoid.
- Antihypertensive medications: MT-II's pressor effect may antagonize therapy; monitor blood pressure.
- Stimulants (amphetamines, pseudoephedrine, high-dose caffeine): Additive sympathetic activation and blood pressure effects.
- MAO inhibitors: Theoretical interaction given melanocortin effects on catecholamine signaling; avoid.
- Other melanocortin agonists (afamelanotide, grey-market α-MSH preparations, PT-141): Redundant pharmacology with additive side effects.
Stop using immediately if:
- Any existing mole shows asymmetry, border irregularity, color variegation, or significant size change (ABCD warning signs)
- New pigmented lesion emerges that is irregular or concerning
- Erection persists longer than 4 hours (priapism — emergency evaluation)
- Chest pain, severe headache, blood pressure persistently > 160/100
- Dark cola-colored urine or diffuse severe muscle pain (rhabdomyolysis concern)
- New-onset hives, facial swelling, difficulty breathing (allergic reaction)
- Significant mood change or suicidal ideation
- Any pregnancy test becomes positive
Mandatory monitoring:
- Dermatologic full-body skin exam with mole mapping before first cycle and at least annually during any repeated use.
- Blood pressure check at baseline and within the first week of each cycle.
- Any new pigmented lesion during a cycle warrants dermatologic evaluation; do not assume it is "just MT-II activity."
Note on medical supervision: Because MT-II is not approved and most US physicians will not prescribe or supervise its use, users are typically navigating these risks alone. At minimum, establish a relationship with a dermatologist who is willing to perform mole mapping without passing judgment — many dermatologists will do this for patients regardless of the reason for concern. The dermatologic surveillance is more important than any other aspect of harm reduction for MT-II users.
Research Disclaimer
This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.
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| Vendor | Product | Form | Qty | Price | $/mg | Coupon | |
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Melanotan II 10mg | vial | 1 vial● In Stock | $35.00BEST | $3.500 | — | |
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Melanotan II 20mg | vial | 1 vial● Out of Stock | $67.00VALUE | $3.350 | — | Sign in for stock alert |
| Golden Spray | spray | 0mg● In Stock | $50.00 | — | |||
| Golden Balm | topical | 0mg● In Stock | $65.00 | — | |||
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Melanotan II 10mg | vial | 10mg vial● In Stock | $34.99 | $3.499 |
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Related Compounds
View AllGHK-Cu
Skin, Hair & AestheticsPhase 2GHK-Cu (copper peptide, glycyl-L-histidyl-L-lysine:copper(II)) is a naturally occurring tripeptide-copper complex with the amino acid sequence Gly-His-Lys chelated to a copper(II) ion.
PT-141 (Bremelanotide)
Skin, Hair & AestheticsFDA ApprovedPT-141 (bremelanotide) is a cyclic 7-amino-acid synthetic melanocortin receptor agonist that acts centrally in the brain — not peripherally on genital tissue — to improve sexual desire, arousal, and responsiveness.
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Quality Indicators
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Quick Facts
Molecular Weight
1024.19 g/mol
CAS Number
121062-08-6
Trial Phase
Preclinical
Safety Profile
Moderate RiskCommon Side Effects
- • Nausea (especially early doses)
- • Facial flushing
- • Fatigue
- • Darkening of existing moles
- • Spontaneous erections
Stop Use If
- History of melanoma or atypical moles
- Cardiovascular disease
- Pregnancy
- Priapism episodes
Research Disclaimer
This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use.
Frequently Asked Questions
How is Melanotan-II different from PT-141 (bremelanotide)?
Both are synthetic melanocortin agonists, but MT-II is a cyclic 7-amino-acid peptide that binds MC1R, MC3R, MC4R, and MC5R roughly equally, while PT-141 is a linear derivative designed for MC4R selectivity. MT-II produces pigmentation (MC1R-driven), appetite suppression and sexual arousal (MC4R), and sebum increase (MC5R); PT-141 produces primarily sexual effects with minimal tanning. PT-141 is FDA-approved as Vyleesi for hypoactive sexual desire disorder in premenopausal women; MT-II has never been approved anywhere. Users who want tanning choose MT-II; users who want sexual-function effects without pigmentation choose PT-141. See the dedicated PT-141 entry for detailed coverage of bremelanotide pharmacology.
Does MT-II replace sunscreen or protect against UV damage?
No. MT-II amplifies the tanning response to UV exposure but does not protect against UV-induced DNA damage, erythema (sunburn), or photoaging. The increased eumelanin deposition from MT-II does provide some additional UV absorption, but this increment is modest compared to what daily SPF 50+ sunscreen provides. Users who skip sunscreen while on MT-II are accumulating UV damage at the same rate as if they had no peptide. A deep MT-II tan coexists with ongoing UV damage — it looks cosmetically protective but is not meaningfully so. Continue rigorous sunscreen use throughout any MT-II cycle and beyond.
Will MT-II cause melanoma?
The honest answer is that we don't know for certain. Multiple dermatology case reports have documented melanoma diagnoses during or after MT-II cycles, and eruptive melanocytic nevi (sudden appearance of multiple new moles) are well-documented. However, MT-II users skew young, fair-skinned, and heavily tanning — a baseline population with elevated melanoma risk regardless of peptide use. What is established: MT-II darkens existing moles, sometimes alters mole morphology to mimic melanoma transformation, and can drive rapid emergence of new pigmented lesions. What is uncertain: whether MT-II actually initiates melanoma or merely changes the visible behavior of lesions that would have developed anyway. The conservative interpretation is that anyone with elevated baseline melanoma risk (personal or family history, many atypical nevi, fair Fitzpatrick type, CDKN2A mutations) should not use MT-II. Everyone using MT-II should have pre- and post-cycle dermatologic mole mapping.
Why does MT-II cause nausea and how do I minimize it?
Nausea is mediated primarily through MC4R activation in the brainstem and area postrema. It is universal at full doses and dose-dependent. The three most effective interventions: (1) Start with very small doses — 100 mcg for the first few injections rather than jumping to 500 mcg — and ramp slowly; tolerance builds with repeated exposure and full doses are usually tolerable by the end of week 1. (2) Dose in the evening, ideally 1-2 hours before sleep, so the 30-90 minute nausea peak occurs during sleep. (3) Avoid alcohol and fatty meals during loading. Antiemetics (ondansetron) are effective but usually unnecessary if the above are followed. Nausea that remains intolerable at low doses after a week suggests MT-II is a poor fit for that individual.
How long does the tan last after stopping MT-II?
MT-II-driven pigmentation fades over 4-6 weeks after cessation as melanin-containing keratinocytes are shed through normal epidermal turnover (~28-day cycle). The baseline tan induced by UV exposure during the cycle fades on the same timeline as any regular tan. Darkened moles, freckles, and age spots may persist longer or partially normalize over months — melanocyte turnover is slower than keratinocyte turnover. Some users report permanent darkening of lips, nipples, and genital skin after repeated cycles; this reflects melanocyte response in those tissues and is not fully reversible. To maintain tan long-term, users either run intermittent MT-II maintenance courses or transition to regular UV exposure (the post-MT-II skin is often somewhat primed and tans faster than pre-MT-II for several months).
Can women use MT-II safely?
Women can and do use MT-II with outcomes similar to men — primarily pigmentation, appetite suppression, and increased libido. Two additional considerations: MT-II is contraindicated in pregnancy (no safety data, teratogenic potential unknown) and should not be used by women actively trying to conceive or who might become pregnant; reliable contraception during any cycle is essential. Second, facial hyperpigmentation (melasma-like patterns) can be more prominent and cosmetically concerning in women, particularly those with existing hormonal melasma or on estrogenic contraceptives. Using MT-II during a melasma-vulnerable period can produce stubborn facial pigmentation that outlasts the cycle. Strict facial sunscreen and avoidance of facial UV exposure during cycles can help.
What is afamelanotide and why is it regulated differently from MT-II?
Afamelanotide (brand name Scenesse, Clinuvel Pharmaceuticals) is an MC1R-selective α-MSH analog approved by FDA in 2019 for erythropoietic protoporphyria (EPP), a rare genetic photosensitivity disorder. Afamelanotide is delivered as a biodegradable subcutaneous implant providing months of MC1R activation, and its selectivity avoids most of the MC4R/MC5R side effects of MT-II. Unlike MT-II, afamelanotide went through rigorous Phase III development, manufacturing QC, and regulatory review. It represents what a properly developed melanocortin drug looks like. Afamelanotide is expensive (~$30,000+ per implant), limited to specific medical indications through certified specialists, and not available for cosmetic tanning. MT-II persists in grey markets precisely because no approved product exists for cosmetic pigmentation at accessible prices.
Is MT-II legal?
Legal status varies by jurisdiction and by context. In the United States, MT-II is not approved by FDA for any use; selling it for human consumption is illegal, but it is commonly sold as a 'research chemical' or 'not for human use' product through online peptide vendors in a regulatory grey zone. Possession for personal use is not criminalized federally but may be in some states. The United Kingdom's MHRA has explicitly warned against MT-II use. Australia's TGA has prosecuted sellers. The European Medicines Agency considers MT-II an unauthorized medicinal product. Customs interception of internationally shipped MT-II is common. This site does not provide legal guidance — anyone considering MT-II should understand both the legal landscape in their jurisdiction and the product-quality risks of grey-market supply.
How do I know if my MT-II product is real?
You largely don't, without third-party testing. Independent HPLC testing services (available through some research analytical labs) can verify peptide identity and approximate purity for a per-sample fee. Short of that, the pragmatic signals: (1) the lyophilized powder should be a fluffy white or pale-yellow pellet or cake, not a loose powder — proper lyophilization produces structure. (2) Reconstituted solution should be perfectly clear and colorless; cloudiness, yellow-brown tint, or visible particulates indicate contamination or degradation. (3) Effects should emerge within the expected dose-response — if 1 mg produces no tanning, no nausea, and no mole darkening after a week, the product is likely under-dosed or not MT-II. (4) Established vendors with years of community reputation and published certificates of analysis are safer than brand-new unknown sellers, though this is not a guarantee. Because product-quality is a primary risk vector, users should assume any grey-market peptide vial is only approximately what it claims to be.
What happens if I stop MT-II mid-cycle?
Nothing dangerous. MT-II has no withdrawal syndrome, no rebound effect, and no physiological dependence. Tan progression halts where it is and gradually fades over 4-6 weeks. Any mole darkening achieved during the partial cycle begins to normalize but may not fully return to baseline. Appetite and sexual side effects resolve within 24-48 hours of the last dose. The only meaningful consequence of stopping mid-cycle is that the inconsistent exposure may have already produced new pigmented lesions or mole changes that will need dermatologic evaluation regardless of continued dosing. If you decide MT-II isn't for you after a few doses, stopping immediately is appropriate — there is no taper needed.
Research Tools
Related Compounds
View AllGHK-Cu
Skin, Hair & AestheticsPhase 2GHK-Cu (copper peptide, glycyl-L-histidyl-L-lysine:copper(II)) is a naturally occurring tripeptide-copper complex with the amino acid sequence Gly-His-Lys chelated to a copper(II) ion.
PT-141 (Bremelanotide)
Skin, Hair & AestheticsFDA ApprovedPT-141 (bremelanotide) is a cyclic 7-amino-acid synthetic melanocortin receptor agonist that acts centrally in the brain — not peripherally on genital tissue — to improve sexual desire, arousal, and responsiveness.
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