Melanotan II
Also known as: MT-II, MT-2, Melanotan 2
Grey-Market Compound. This compound is not approved by the FDA or any major regulatory authority. No established regimen exists. Products available outside of regulated channels lack standardized manufacturing, quality control, and potency verification. Consult a qualified clinician. Research-only risks apply.
Overview
Clinical Summary
Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (alpha-MSH). It is a non-selective melanocortin receptor agonist that activates MC1R (skin pigmentation), MC3R and MC4R (sexual arousal and appetite), and MC5R (exocrine function). Originally developed at the University of Arizona for photoprotective tanning, melanotan II was found to produce sexual arousal as a prominent side effect, leading to the development of bremelanotide (PT-141) as a more selective derivative for sexual dysfunction. Melanotan II is widely used in the grey market for tanning and sexual enhancement, but it carries significant safety concerns including nausea, blood pressure changes, and alterations in nevi that may indicate melanoma risk.
Plain Language Summary
Melanotan II is a peptide that causes skin tanning without UV exposure and also increases sexual arousal. It works by activating melanocortin receptors throughout the body. While it is popular in the grey market for tanning and sexual enhancement, it has serious safety concerns. Common side effects include severe nausea and changes in blood pressure. More concerning, it can cause moles to darken or change, raising worries about melanoma risk. It is not approved for any use and a safer derivative (bremelanotide/Vyleesi) was developed for sexual dysfunction instead.
Mechanism of Action
Melanotan II is a cyclic lactam analogue of alpha-MSH with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. It is a non-selective agonist at melanocortin receptors MC1R through MC5R. MC1R activation on melanocytes stimulates eumelanin production, causing skin tanning independently of UV radiation. MC3R and MC4R activation in the hypothalamus and limbic system mediates sexual arousal, erectile function, and appetite suppression. The non-selectivity of melanotan II is responsible for both its broad effects and its side effect burden. Unlike the more selective bremelanotide (which primarily targets MC3R/MC4R), melanotan II produces significant pigmentation changes alongside its sexual effects.
Evidence Summary
Wessells et al. (1998) conducted a small double-blind crossover trial showing that subcutaneous melanotan II produced erections in 8 of 10 men with erectile dysfunction versus 1 of 10 with placebo. This trial also documented dose-dependent tanning and significant nausea. Brennan et al. (2014) reviewed the pharmacology and widespread grey-market use. Multiple case reports have documented nevus changes and potential melanoma associations. The compound was not pursued for clinical development due to its non-selectivity and side effect profile; instead, bremelanotide was developed as a more selective MC4R agonist for sexual dysfunction.
Safety Profile
Melanotan II carries significant safety concerns. Nausea is extremely common and can be severe, occurring in the majority of users. Blood pressure elevation has been documented. The most concerning safety signal involves changes in existing nevi (moles), including darkening, enlargement, and development of dysplastic features. Multiple dermatological case reports have raised concern about potential melanoma acceleration, though a direct causal link has not been established in controlled studies. Facial flushing, fatigue, and yawning are also common. The non-selective melanocortin activation underlies most of these effects.
Contraindications
- History of melanoma or dysplastic nevi
- Known hypersensitivity to melanocortin peptides
- Uncontrolled hypertension
- Cardiovascular disease
- Pregnancy and breastfeeding (no safety data)
Adverse Events
- Nausea and vomiting (very common, often severe)
- Facial flushing
- Blood pressure elevation
- Darkening of existing moles and nevi
- New mole development
- Fatigue and yawning
- Spontaneous erections
- Decreased appetite
- Injection site reactions
Interactions
- Antihypertensive medications (melanotan II may raise blood pressure)
- PDE5 inhibitors (additive erectile effects, potential cardiovascular risk)
- No formal drug interaction studies
Active Safety Signals
Melanotan II is a non-selective melanocortin agonist that stimulates melanogenesis independently of UV exposure. Multiple case reports document darkening, enlargement, or dysplastic changes in pre-existing nevi following melanotan II use. There is theoretical concern that stimulating melanocyte activity could accelerate progression of subclinical melanoma. Several dermatological societies have issued warnings against its use. Blood pressure elevation and severe nausea are also common acute adverse effects.
Regulatory Notes
Melanotan II is not approved in any jurisdiction. Multiple regulatory agencies (FDA, TGA, MHRA, EMA) have issued warnings against its use. It is classified as an unapproved therapeutic good in Australia. The more selective derivative bremelanotide (Vyleesi) received FDA approval for HSDD in 2019. Grey-market melanotan II is manufactured without quality controls and purity is unverified.
Monitoring Considerations
Full-body dermatological examination including dermoscopy before and during use. Blood pressure monitoring. Patients should photograph all existing moles before use and monitor for any changes in size, shape, or color. Any nevus changes should prompt immediate dermatological evaluation. Cardiovascular assessment in at-risk individuals.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
Grey-market preparations are supplied as lyophilized powder in multi-use vials. Reconstitute with bacteriostatic water. Store reconstituted solution at 2 to 8 degrees C and use within 4 to 6 weeks (vendor guidance, not validated). Protect from light. No pharmaceutical-grade stability data available. Peptide quality from grey-market sources is highly variable.
References
- 1RCT
Effects of Melanotan II on Erection in Men with Erectile Dysfunction
Wessells H, Fuciarelli K, Hansen J, et al. (1998). Journal of Urology
Key findings: Double-blind crossover trial demonstrated that subcutaneous melanotan II produced clinically meaningful erections in 8 of 10 men with erectile dysfunction vs. 1 of 10 with placebo. Dose-dependent tanning also observed.
Limitations: Very small sample size (n=10). Short duration. Significant nausea. Led to development of bremelanotide as a more selective analogue.
View source - 2review
Melanotan II: A Review of Its Pharmacology, Safety, and Effects on Pigmentation and Sexual Function
Brennan R, Wells JG, Van Hout MC. (2014). Human Psychopharmacology
Key findings: Review highlighting widespread grey-market use of melanotan II for tanning and sexual enhancement. Documents safety concerns including nausea, blood pressure changes, mole darkening, and potential melanoma risk.
Limitations: Observational and self-report data predominate. No controlled long-term safety studies.
View source - 3review
Melanocortin Peptides and Skin: From Alpha-MSH to Synthetic Analogues
Dorr RT, Lines R, Levine N, et al. (1996). Annals of the New York Academy of Sciences
Key findings: Early review of melanocortin-based tanning agents including melanotan I and II. Describes mechanism of MC1R activation and UV-independent melanogenesis.
Limitations: Pre-dates most clinical safety data. Early pharmacological characterization.
Last reviewed: 2026-03-24 | Version: 1 | Status: Published