Compound reference
Melanotan II
Also known as MT-II
A non-selective melanocortin agonist first developed for sunless tanning, then abandoned when it reliably triggered erections — the effect that seeded PT-141. Today it is an unapproved, WADA-banned gray-market injectable used for tanning, appetite suppression, and libido, with a real record of serious harms.
- CAS
- 121062-08-6
- Sequence
- Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ — a cyclic lactam heptapeptide analogue of α-MSH
Unapproved research peptide; not FDA-approved as a drug or tanning product.
Mode of action
Melanotan II is a cyclic, truncated analogue of α-melanocyte-stimulating hormone (α-MSH). Where the approved tanning peptide Melanotan I is comparatively MC1R-selective, Melanotan II is a non-selective agonist across the melanocortin receptors — MC1R, MC3R, MC4R and MC5R — and that breadth is the root of both its wide-ranging effects and its side-effect load. MC1R activation on melanocytes drives eumelanin synthesis (tanning); central MC4R and MC3R activation in the hypothalamus suppresses appetite and, distinctively, initiates erections and sexual arousal through a central pathway that does not require sexual stimulation. The same non-selective agonism produces sympathomimetic and vasoconstrictive effects in the periphery. Its cyclic lactam structure makes it more potent and longer-acting than native α-MSH.
Main intended effect
Skin tanning through stimulation of melanin production. In real-world use it is also taken for its appetite-suppressing and libido- and erection-enhancing effects.
Areas of interest
The historical research interest was twofold — sunless tanning (its original purpose) and erectile dysfunction, after the erectogenic side effect emerged in early studies and led directly to the development of the analogue PT-141 (bremelanotide). Contemporary interest is almost entirely non-clinical: Melanotan II is a popular gray-market injectable in cosmetic-tanning and bodybuilding circles, nicknamed the "Barbie drug" for its combined tanning, appetite-suppressing and libido effects.
Evidence for intended effects
The human evidence is thin and dated. A pilot phase I study (Dorr and colleagues, 1996) showed that low subcutaneous doses produce measurable tanning in volunteers, and earlier rat work characterised its pharmacokinetics. The clearest controlled human signal is actually for erections, not tanning: a small double-blind crossover trial (Wessells, 1998) found a single 0.025 mg/kg subcutaneous dose initiated clinically apparent erections in 8 of 10 men with psychogenic erectile dysfunction (mean tip-rigidity duration 38 vs 3 minutes with placebo). Its melanocortin pharmacology is well characterised in reviews, and it is used preclinically as a research probe of melanocortin–dopamine circuitry. What does not exist is any large, modern efficacy or safety trial — and Melanotan II has never been approved for any indication by any regulator.
| Strand | What exists | Tier |
|---|---|---|
| Tanning | Pilot phase I (1996); rat PK | Limited, dated |
| Erections / sexual function | Small crossover RCT (1998) | Limited human; basis for PT-141 |
| Mechanism | Non-selective MC1/3/4/5R agonism | Well characterized |
| Approval (any indication) | None | Unapproved |
Studied amounts (literature dosing context)
Reported amounts are from early studies, not recommendations: the pilot tanning work used low subcutaneous doses, and the erectile-dysfunction crossover trial used a single 0.025 mg/kg subcutaneous dose. There is no approved dose and no established safe regimen, and this page does not provide dosing guidance.
Safety and regulatory status
Melanotan II has a documented record of serious harm, much of it traceable to non-selective melanocortin agonism and its sympathomimetic and vasoconstrictive effects. Published case reports include systemic toxicity with rhabdomyolysis after supratherapeutic dosing, acute ischaemic priapism requiring surgical management, acute renal infarction, and oral-mucosal pigmentation — alongside the class-wide concern of darkening and eruptive melanocytic naevi and changes in pre-existing moles. Because it is injected and sourced online, infection and contaminated or mislabelled product add further risk.
Regulatorily, Melanotan II is not approved by any governmental health authority for human use anywhere. It is captured under class S0 (non-approved substances) of the WADA Prohibited List, carrying a presumptive four-year ban with no therapeutic-use exemption available, and unauthorised injectable Melanotan-2 has been explicitly named in regulatory seizures (for example by Health Canada in 2025). Material sold as "Melanotan 2" is an unregulated research chemical of unverified identity and purity.
Sources
Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study
Dorr and colleagues conducted an early pilot phase I study of Melanotan II — a cyclic heptapeptide analog of α-MSH — in male volunteers given escalating subcutaneous doses, establishing that the peptide has superpotent melanotropic activity in vitro and produces tanning in humans at low subcutaneous doses. Reported adverse effects were mild nausea and dose-dependent somnolence and fatigue, together with a characteristic stretching-and-yawning complex that correlated with spontaneous penile erections lasting 1–5 hours — the observation that ultimately redirected MT-II development toward sexual-dysfunction indications and the analog PT-141 (bremelanotide). This is a small, early-phase study; Melanotan II is not an approved drug.
Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo-controlled crossover study
Double-blind, placebo-controlled crossover trial (Wessells and colleagues, J Urol 1998) of a single subcutaneous injection of Melanotan II at 0.025 mg/kg in 10 men with psychogenic erectile dysfunction of no known organic cause, with real-time RigiScan monitoring over a 6-hour period. Clinically apparent erections developed in 8 of 10 men with Melanotan II; mean duration of tip rigidity greater than 80% was 38.0 minutes versus 3.0 minutes with placebo (p = 0.0045). Erections occurred centrally through melanocortin receptor activation, independent of sexual stimulation. Transient adverse effects — nausea, stretching and yawning, and decreased appetite — were reported more frequently with Melanotan II than placebo but none required treatment. The authors concluded that Melanotan II is a potent erection initiator in psychogenic erectile dysfunction with manageable side effects at the tested dose.
A comparison of HPLC and bioassay methods for plasma melanotan-II (MT-II) determination: application to a pharmacokinetic study in rats
Ugwu and colleagues characterized the pharmacokinetics of Melanotan II in rats after a single intravenous dose and validated the analytics by comparing an HPLC assay with a bioassay, finding a significant linear correlation (r = 0.90, p < 0.001) and comparable disposition profiles and pharmacokinetic parameters between the two methods. MT-II showed a biphasic disposition — a two-phase decline in plasma concentration over time. This is an early preclinical pharmacokinetic and analytical-method study in rats that helped establish quantitation for later MT-II development; it carries no human or efficacy data.
Functional interaction between the dopamine and melanocortin systems of the brain
Derkach, Romanova, and Shpakov present rodent evidence for crosstalk between the brain melanocortin and dopamine systems, using the non-selective melanocortin-receptor agonist Melanotan II as a pharmacological probe. Injection of Melanotan II into the ventral tegmental area dose-dependently suppressed food and sucrose-solution consumption in rats, and prolonged intracerebroventricular Melanotan II produced significant, brain-region-dependent changes in dopamine D1R and D2R gene expression; neonatal Melanotan II treatment of voles produced more marked mating motivation in adult females, indicating gender-specific effects on dopaminergic regulation. The work uses MT-II as a research tool to dissect circuitry rather than as a candidate therapeutic. Findings are preclinical (rodent) and mechanistic.
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization
Hadley and Dorr review the development of melanocortin peptide therapeutics, tracing milestones from α-MSH biology through clinical candidates and commercialization. Melanotan I, a linear superpotent α-MSH analog, was advanced for skin tanning and potential reduction of skin-cancer risk, while Melanotan II, a cyclic truncated analog, was originally tested for tanning but — owing to its erectogenic side effect — was redirected toward male erectile dysfunction; the MT-II-derived analog PT-141 (bremelanotide) was then developed and commercialized for sexual dysfunction in both sexes. Written by investigators central to the field, this is a historical and commercialization review rather than primary data.
An unhealthy glow? A review of melanotan use and associated clinical outcomes
Brennan, Wells, and Van Hout reviewed the literature on Melanotan I and Melanotan II, synthesizing eighteen clinical trials and twenty-one clinical case presentations to characterize the effects and harms of these synthetic melanotropic "synthetic-tanning" peptides. Reported adverse outcomes include nausea, darkening of existing naevi, yawning, a systemic sympathomimetic toxidrome, and melanoma. The authors emphasize that much of the harm stems from online sourcing of unregulated product — exposing users to bloodborne-virus and injection-site infection risk and to contaminated or mislabelled contents — set against socio-cultural pressure to be tanned and black-market diversion of MT-I/MT-II. This is a narrative clinical-outcomes review; both peptides are unlicensed and not approved for cosmetic tanning.
Use of melanotan I and II in the general population
Evans-Brown and colleagues describe the spread of the synthetic melanocortin analogues Melanotan I and Melanotan II into general, non-clinical use, driven by their skin-tanning effects and — for MT-II — induction of penile erections and increased sexual desire. The authors note the drugs are unlicensed yet easily obtained online and sold or administered in tanning salons, beauty parlours, and hairdressers, and they summarize development status: Melanotan I (afamelanotide) was in phase III trials as a photoprotective agent, while Melanotan II had earlier been developed for sexual dysfunction, yielding the analog/metabolite bremelanotide (PT-141). This is a short BMJ awareness piece on unregulated population use; both peptides were unlicensed for cosmetic use.
Melanotan
Mahiques-Santos's opinion article frames melanotan for dermatologists. It explains that melanotan is a synthetic α-MSH analog and distinguishes Melanotan I ([Nle4-D-Phe7]-α-MSH, a 13-amino-acid linear peptide, more melanin-selective, developed as the photoprotectant afamelanotide/SCENESSE) from Melanotan II (a shorter lactam-ring cyclic analog, less receptor-selective, which also suppresses appetite and increases libido and seeded the PT-141 program). The author reviews potential medical uses (photoprotection in erythropoietic protoporphyria and other photodermatoses; central erectogenic activity), then details black-market "Barbie drug" use and its harms — eruptive melanocytic naevi, changes in pre-existing nevi, a reported melanoma (without established causation), hypertension, and injection/needle-sharing infection risk — and advises clinicians to suspect, investigate, and report illicit use. An opinion/review article; unlicensed cosmetic use is discouraged pending completion of clinical trials.
The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases
Peer-reviewed survey by Cai and Hruby (Curr Protein Pept Sci, 2016) of the five melanocortin G-protein-coupled receptors (MC1R–MC5R), their POMC-derived endogenous agonists (alpha-, beta-, and gamma-MSH and ACTH), and their tissue distribution and physiological functions relevant to multiple degenerative diseases. The authors characterise the conserved His-Phe-Arg-Trp pharmacophore shared by all endogenous ligands, explaining why achieving receptor-subtype selectivity in drug design is particularly challenging. Peptide, non-peptide, and peptidomimetic approaches to selective ligand design are reviewed, covering therapeutic targets including obesity (MC3R/MC4R), sexual dysfunction (MC4R), inflammation (MC1R/MC3R), and photoprotection (MC1R). The review underscores the broad translational potential of the melanocortin system while noting that the evolutionary conservation of the binding pharmacophore constitutes a fundamental obstacle to subtype selectivity.
Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin
Comprehensive review by Yuan and Tao (Biomolecules, 2022) cataloguing melanocortin receptor ligands beyond the classical endogenous agonists alpha-MSH and ACTH. The authors organise ligands into four categories: classical (MSH variants and agouti-related peptide), nonclassical (lipocalin 2, beta-defensin, small molecules, pharmacoperones), and clinically approved agents (ACTH, setmelanotide for monogenic obesity, bremelanotide for hypoactive sexual desire). MC3R and MC4R, characterised as "neural MCRs" highly expressed in the CNS, are highlighted as the primary targets for metabolic and sexual function indications. The review places Melanotan 2 (a non-selective agonist of MC1R, MC3R, MC4R, and MC5R) in the context of the selectivity profile distinguishing it from approved selective agents. The authors note that developing highly selective ligands for individual receptor subtypes remains an ongoing challenge given the conserved His-Phe-Arg-Trp pharmacophore.
Novel Emerging Therapies for Erectile Dysfunction
Peer-reviewed narrative review examining experimental erectile dysfunction therapies beyond established PDE5 inhibitors and penile implants, covering centrally acting melanocortin receptor agonists, Max-K channel activators, guanylate cyclase activators, nitric oxide donors, stem cell regenerative approaches, and low-intensity shock wave therapy. Melanocortin receptor agonists are identified as centrally acting agents showing promising results by initiating erection without requiring sexual stimulation, with particular relevance for patients unresponsive to PDE5 inhibitors; this mechanistic class provides direct context for Melanotan II and its successor bremelanotide (PT-141). Stem cell therapy and shock wave treatment showed favorable outcomes in specific ED subtypes including diabetic, post-prostatectomy, and vasculogenic etiologies. The authors conclude that these emerging modalities can address needs of patients unresponsive to current therapies, but that most still require validation through well-designed clinical trials with established long-term safety profiles.
Melanotan II injection resulting in systemic toxicity and rhabdomyolysis
Case report published in Clinical Toxicology (2012) describing systemic toxicity and rhabdomyolysis in a 39-year-old Caucasian male who self-administered a single 6 mg subcutaneous dose of Melanotan 2 — six times the recommended starting dose. The patient presented with diffuse myalgias, diaphoresis, mydriasis, tachycardia, and muscle tremors consistent with sympathomimetic toxidrome. Creatine phosphokinase rose from 1,760 IU/L on presentation to 17,773 IU/L at 12 hours, alongside creatinine elevation and urinalysis findings consistent with myoglobinuria. Management included benzodiazepines for agitation and IV fluid with sodium bicarbonate for rhabdomyolysis; the patient was discharged from the ICU after 3 days with improving renal and CK values. The case illustrates dose-dependent sympathomimetic and musculoskeletal toxicity from supraphysiological non-selective melanocortin agonism.
Melanotan Tanning Injection: A Rare Cause of Priapism
Case report published in Sexual Medicine (2021) describing acute ischemic priapism following subcutaneous injection of Melanotan 2, used off-label for tanning. The case required escalating urological intervention: initial cavernosal aspiration and irrigation with intracavernous phenylephrine failed to achieve detumescence, necessitating operative management with penoscrotal decompression. The authors note that priapism had been reported only twice previously in association with Melanotan 2, making this a rare but recognized complication of the non-selective melanocortin receptor agonism that underlies the peptide's pro-erectile activity. The case illustrates that centrally mediated MC4R activation can precipitate a urological emergency requiring surgical management.
Melanotan II: a possible cause of renal infarction: review of the literature and case report
Case report and literature review published in CEN Case Reports (2020) describing right-sided acute renal infarction confirmed on CT imaging in a middle-aged male following Melanotan 2 use. The authors propose two pathways contributing to the event: thrombotic pharmacological effects and a possible direct toxic effect on the renal parenchyma driven by non-selective peripheral melanocortin-receptor activation with sympathomimetic and vasoconstrictive consequences. The review notes that Melanotan 2-associated rhabdomyolysis and renal failure have been documented in prior cases. Renal infarction is characterized as a potentially life-threatening condition that is frequently misdiagnosed or diagnosed late, elevating the clinical significance of this complication.
Changes in Oral Mucosa Associated with Melanotan II Injections: A Case Report
Case report published in Life (MDPI, 2026) documenting drug-induced oral mucosal pigmentation in a patient who self-administered Melanotan 2 injections over 64 days. Brown pigmentation developed across the attached gingiva of both maxillary and mandibular arches — most intense in the anterior mandible — and on the bilateral buccal mucosa with irregular borders; the tongue was unaffected. At 28 days post-cessation, buccal mucosal pigmentation had largely resolved, but gingival hyperpigmentation persisted with reduced intensity at 90-day follow-up. The authors highlight that persisting gingival pigmentation may obscure or mimic pathological intraoral lesions, and note a lack of published data on the resolution timeline for Melanotan 2-associated oral pigmentation.
WADA Prohibited List 2026 — Non-Approved Substances (S0)
The World Anti-Doping Agency (WADA) 2026 Prohibited List, approved September 2025 and effective 1 January 2026, includes class S0 (Non-Approved Substances), which prohibits at all times any pharmacological substance not currently approved by any governmental regulatory health authority for human therapeutic use. Melanotan 2 (MT-2) lacks approval by any such authority worldwide and is therefore captured under S0 regardless of whether it is individually named. S0 is structured as a category prohibition rather than an enumerated list, meaning any unapproved substance with a pharmacological structure or mechanism falls within its scope. S0 substances are non-specified, and a violation carries a presumptive four-year ban. No therapeutic use exemption is obtainable for MT-2 because there is no authorized therapeutic indication against which to grant one.
Unauthorized injectable peptide drugs seized from Optimum Wellness Centre in Calgary, Alberta may pose serious health risks
Health Canada safety alert dated April 1–2, 2025 reporting the seizure of 26 unauthorized injectable peptide drug products from Optimum Wellness Centre in Calgary, Alberta. Melanotan-2 and Melanotan-I are among the explicitly named products, alongside ARA 290, BPC-157, CJC-1295, ipamorelin, PT-141, and Thymosin variants. Health Canada confirmed that none of the seized products had been authorized by the agency, meaning they were not assessed for safety, efficacy, or quality and were illegal to sell in Canada. Stated risks include infection, allergic reactions, drug interactions, potentially dangerous ingredients or contaminants, and unsafe manufacturing or storage conditions. Recipients were advised to consult a healthcare professional and to verify authorized products through the presence of a Drug Identification Number (DIN), Natural Product Number (NPN), or DIN-HM.