A non-selective melanocortin agonist with serious safety baggage
Injection · 503A Compounding
Educational content. This page describes Melanotan 2 for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
Researched and maintained by the PepHookup team. Regulatory status last verified April 12, 2026.
Melanotan 2 (MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (alpha-MSH). It grew out of structure-activity work at the University of Arizona in the late 1980s, where researchers led by Victor Hruby and Mac Hadley truncated alpha-MSH and used molecular dynamics to design potent, prolonged-acting cyclic lactam analogues. The molecule is closed into a ring through a lactam bridge between aspartate and lysine side chains, which gives it metabolic stability and a compact shape.
Unlike linear Melanotan 1 (afamelanotide, a 13-amino-acid peptide that is selective for MC1R), MT-II is non-selective and its compact cyclic structure lets it reach central melanocortin receptors. That central activity is the source of its sexual and appetite effects, and also the reason it carries side effects that the more selective analogues do not. MT-II has never been approved by the FDA or any major regulatory agency. It served as the chemical parent for bremelanotide (PT-141), which was engineered to isolate the sexual-function effects.
MT-II binds G-protein-coupled melanocortin receptors and raises intracellular cyclic AMP, driving protein kinase A dependent signaling. The downstream consequences depend on which receptor subtype is engaged and where in the body it sits.
At MC1R on skin melanocytes, raised cAMP activates CREB and upregulates microphthalmia-associated transcription factor (MITF), the master regulator of pigmentation, which in turn increases tyrosinase expression and pushes melanin synthesis toward eumelanin. At MC4R in the hypothalamus and spinal cord, activation triggers erectile signaling through nitric oxide dependent pathways and suppresses appetite through satiety circuits. MC3R contributes to energy homeostasis, and MC5R influences exocrine gland function.
The non-selective profile is the whole story. Because a single dose lights up all four receptor subtypes at once, pigmentation, sexual arousal, appetite suppression, nausea, and flushing tend to arrive together rather than in isolation. This is precisely why afamelanotide was developed for MC1R-selective pigmentation and PT-141 for MC4R-driven sexual function, leaving MT-II itself without a clean clinical niche.
A non-selective melanocortin agonist with serious safety baggage
MT-II is a non-selective melanocortin receptor agonist. At MC1R it drives eumelanin synthesis and skin darkening; at MC4R it stimulates erectile signaling via central nitric oxide pathways and suppresses appetite; at MC3R and MC5R it modulates energy homeostasis and exocrine function. Its cyclic structure enables the central receptor access that distinguishes it from linear afamelanotide.
Subcutaneous doses escalated to 0.025-0.03 mg/kg over two weeks increased facial, upper-body, and buttock pigmentation by quantitative reflectance in 2 of 3 subjects. Spontaneous penile erections occurred 1 to 5 hours after dosing, often preceded by stretching and yawning. Mild nausea appeared at most dose levels and somnolence at the highest dose. The authors recommended 0.025 mg/kg/day for future work.
Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME · Life Sci, 58(20):1777-1784 (1996) · PubMed
8 of 10 men developed clinically apparent erections without sexual stimulation. Mean duration of tip rigidity above 80% was 38.0 minutes with MT-II versus 3.0 minutes with placebo (p = 0.0045). Transient nausea, stretching, yawning, and reduced appetite were more frequent on active drug but required no intervention.
Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N · J Urol, 160(2):389-393 (1998) · PubMed
MT-II produced subjectively reported erections after 12 of 19 injections versus 1 of 21 placebo doses. Mean tip rigidity above 80% lasted 45.3 minutes with MT-II versus 1.9 minutes with placebo (p = 0.047), and sexual desire increased significantly. Four injections caused severe nausea.
Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N · Urology, 56(4):641-646 (2000) · PubMed
MT-II led to penile erection in 17 of 20 men without sexual stimulation, with roughly 41 minutes of tip rigidity above 80%. Increased sexual desire followed 13 of 19 active doses versus 4 of 21 placebo doses (68% versus 19%). Severe nausea occurred in about 13% of subjects at 0.025 mg/kg.
Wessells H, Levine N, Hadley ME, Dorr R, Hruby V · Int J Impot Res, 12(Suppl 4):S74-S79 (2000) · PubMed
start low, go slow
Subcutaneous Injection (clinical trial protocol)
Subcutaneous Injection (clinical trial protocol): This was the dose recommended after the first-in-human study. Higher doses produced severe nausea, and no formal dose-finding program was ever completed. Any dosing for an individual would be determined by a licensed provider, not self-selected from these figures.
All published dosing comes from small Phase I and early crossover studies. No Phase II or III dose-finding trials were ever completed, so there is no validated therapeutic dose for any indication.
MT-II is not approved by the FDA or any major regulatory agency. The FDA, Australia's TGA, and other authorities have issued public warnings against products sold as tanning injections.
Material sold online has been chemically analyzed and found to contain less peptide than labeled and measurable impurities, so the actual dose delivered by an unregulated vial is unknown and unreliable.
Because every dose activates all four melanocortin receptors at once, side effects such as nausea, flushing, and spontaneous erections tend to accompany the intended pigmentation effect rather than being avoidable.
MT-II's safety profile is the main reason it never advanced through approval. Beyond routine peptide side effects, case reports document rhabdomyolysis with kidney injury, ischemic priapism, and posterior reversible encephalopathy syndrome, several of them following self-administered doses larger than those used in the supervised trials.
The relationship between MT-II and melanoma remains unresolved. Several case reports describe melanoma or eruptive dysplastic nevi emerging during or shortly after use, though most patients also had fair skin, heavy UV or sunbed exposure, and family history. A dermatology review concluded that much of the excess risk reflects the sun-seeking behavior that accompanies use rather than the peptide itself, while noting that MT-II does stimulate melanocyte proliferation and darkens existing moles, which regulators treat as a legitimate concern.
Commercially available MT-II is unregulated. Laboratory analysis of products sold online found vials containing well below the labeled amount of peptide plus unidentified impurities. Shared injecting equipment adds a bloodborne-virus risk on top of contamination and mislabeling.
MT-II is not a substitute for medical care, and the information here is educational. Whether it is appropriate for a given person, and at what dose, is a decision for a licensed provider who can weigh these documented risks.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Melanotan 2 | Pigmentation and sexual function (no approved use) | Subcutaneous injection | About 2 weeks in published trials | Non-selective melanocortin agonist that produces tanning, sexual arousal, and appetite suppression together, paired with safety concerns that kept it from approval and led regulators to flag it |
| PT-141 (Bremelanotide) | Sexual Health | Injection (as-needed) | Ongoing as-needed | The only FDA-approved on-demand HSDD treatment that works centrally through melanocortin and dopamine pathways rather than peripheral blood flow |
| Melanotan 1 (Afamelanotide) | Photoprotection in EPP | Subcutaneous implant | Every 2 months (ongoing) | The only FDA-approved melanocortin agonist, pairing eumelanin induction with UV-independent DNA repair through a selective MC1R mechanism |
| AHK-Cu | Hair & Skin Regeneration | Topical | 8 to 12 weeks | A hair follicle-focused copper tripeptide with a single supporting laboratory study and a biphasic dose response that makes formulation precision matter |
The FDA placed this substance in Category 2 of the 503A bulk drug substances evaluation, flagging significant safety risks. 503A compounding carries FDA enforcement risk, so most pharmacies decline to prepare it and many physicians hesitate to prescribe it.
In April 2026, HHS Secretary Robert F. Kennedy Jr. announced that nominators withdrew 12 peptides from Category 2 of the FDA's 503A bulk drug substances evaluation, including this one. The FDA referred them to its Pharmacy Compounding Advisory Committee (PCAC) for re-evaluation at meetings beginning July 2026. If PCAC recommends Category 1 status and the FDA agrees, licensed 503A pharmacies could compound it under FDA enforcement discretion again. The outcome is not final.
Listed in Category 2. FDA and international regulatory agencies have flagged serious risks including potential melanoma induction, posterior reversible encephalopathy syndrome, and sympathomimetic toxidrome. Not approved for any indication and not eligible for compounding.
Listed as 'Melanotan II' in 503A Category 2
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ “Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics.” J Med Chem, 32(12):2555-2561 (1989)
Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME “Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.” Life Sci, 58(20):1777-1784 (1996)
Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N “Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study.” J Urol, 160(2):389-393 (1998)
Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N “Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction.” Urology, 56(4):641-646 (2000)
Wessells H, Levine N, Hadley ME, Dorr R, Hruby V “Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.” Int J Impot Res, 12(Suppl 4):S74-S79 (2000)
Hadley ME, Dorr RT “Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.” Peptides, 27(4):921-930 (2006)
Ückert S, Bannowsky A, Albrecht K, Kuczyk MA “Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies.” Expert Opin Investig Drugs, 23(11):1477-1483 (2014)
Nelson ME, Bryant SM, Aks SE “Melanotan II injection resulting in systemic toxicity and rhabdomyolysis.” Clin Toxicol (Phila), 50(10):1169-1173 (2012)
Habbema L, Halk AB, Neumann M, Bergman W “Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review.” Int J Dermatol, 56(10):975-980 (2017)
Devlin J, Pomerleau A, Foote J “Melanotan II overdose associated with priapism.” Clin Toxicol (Phila), 51(4):383 (2013)
Looking into Melanotan 2? Find a provider who knows this peptide and can walk you through your options.
Find a ProviderA linear α-MSH analog that selectively activates MC1R to drive photoprotective pigmentation.
FDA-approved as Scenesse, a subcutaneous implant used in erythropoietic protoporphyria.
A copper-bound tripeptide that stimulates fibroblast proliferation and follicle signaling.
Used in cosmetic and hair-regeneration formulations; not on any FDA bulks list for compounding.
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