Melanotan 2: Safety Profile & Research Summary
24 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: February 2026
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Côté et al. (2017) | F344BN rats — ICV 0.04–1 µg/day × 40d | Fat pads -35% to -55% (p<0.01/0.001); iBAT thermogenesis 3-fold ↑; food intake returned to normal by day 5 — weight loss via ↑ energy expenditure | [6] |
| Vemulapalli et al. (2001) | NZW rabbits — 66–133 µg/kg IV | Cavernosal pressure 3.2-fold ↑ (p<0.05); abolished by MC3/4 antagonist SHU 9119, pudendal nerve transection, or L-NAME → centrally-mediated NO release | [5] |
| Minakova et al. (2019) | MIA autism-model mice — ICV 2.5 µg/day × 7d | Sociability index 3.1 → 26.3 (p<0.0001); anxiety unchanged; rescued social deficits to control levels | [11] |
| Ford et al. (2024) | Prairie voles (WT vs Oxtr-KO) — IP/ICV | Social context → NAcc Fos ↑ (p<0.01) in WT but NOT Oxtr-KO; non-social → PVN activation only → oxytocin-dependent social learning mechanism | [7] |
| Jain et al. (2018) | C57BL/6J mice — 10 mg/kg IP | Plasma histamine 4-fold ↑ (p<0.0001); profound hypothermia abolished in mast cell-deficient mice; SC route ↓ histamine 63% | [8] |
| Eliason et al. (2022) | C57BL/6J mice — NAcc microinjection | All doses ↓ food intake at 1,2,4,6h (p<0.05); decreased lever-pressing motivation; no aversive state or metabolic rate change | [10] |
| Wu et al. (2020) | B16-F10 melanoma mice — topical | Dramatically slowed tumor growth; ↑PTEN, ↓COX-2/PGE2, induced cell death; inhibited migration/invasion | [14] |
Human Clinical Data
| Study | Population | Key Results | Ref |
|---|---|---|---|
| Dorr et al. (1996) — Phase I | n=3 healthy males; 0.01–0.025 mg/kg SC | Visible tanning in 2/3 subjects; spontaneous erections 1–5h post-dose; mild nausea; recommended Phase I dose: 0.025 mg/kg | [1] |
| Wessells et al. (1998) — Psychogenic ED | n=10 men; 0.025 mg/kg SC, double-blind crossover | 80% response rate; tip rigidity >80% for 38 min vs 3 min placebo (p=0.0045) | [3] |
| Wessells et al. (2000) — Organic ED | n=10 men; 0.025 mg/kg SC, double-blind crossover | 63% erection rate (12/19 injections vs 1/21 placebo); tip rigidity >80% for 45.3 min vs 1.9 min (p=0.047); enhanced sexual desire | [9] |
Safety Concerns — Case Reports (Unregulated Use)
| Event | Details | Ref |
|---|---|---|
| Priapism | 22-hour painful erection (unknown dose); 60-year-old required surgical shunting after 10 mg injection | [15] |
| Rhabdomyolysis | 39-year-old male: 6 mg SC → CPK 17,773 IU/L; tachycardia, hypertension, agitation, renal dysfunction | [16] |
| Renal Infarction | 45-year-old male: 50% right kidney infarction after 10 mg injections; likely sympathomimetic vasoconstriction | [17] |
| Melanoma/Nevi Changes | 16-year-old female (FAMMM): darkened/enlarged nevi + dysplastic nevus after 2 months (0.5 mg/day); melanoma in situ reports | [18] |
| Common Side Effects | Nausea (dose-dependent), facial flushing, fatigue, yawning/stretching, decreased appetite, darkened moles | [1] |
Pharmacokinetics & Dosing Summary
| Parameter | Value |
|---|---|
| Human Half-Life | ~1–2 hours (enhanced vs α-MSH by cyclic structure) |
| BBB Penetration | Yes (unlike Melanotan I) |
| Active Metabolite | Bremelanotide (PT-141) — deaminated, lacks C-terminal amide |
| ED Research Dose | 0.025 mg/kg SC (Phase I optimal for erection with manageable side effects) |
| Contraindications | Cardiovascular disease; personal/family melanoma history; PDE5 inhibitor combination (priapism risk) |
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
References
- Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences. 1996;58(20):1777-1784.
- Hadley ME, Dorr RT. Melanocortin peptide therapeutics: Historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-930.
- Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: Double-blind, placebo controlled crossover study. The Journal of Urology. 1998;160(2):389-393.
- FDA Warning Letters regarding unauthorized marketing of Melanotan products.
- Vemulapalli R, Kurowski S, Salisbury B, et al. Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO. British Journal of Pharmacology. 2001;134(8):1705-1710.
- Côté I, et al. Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction. Canadian Journal of Physiology and Pharmacology. 2017.
- Ford CL, McDonough AA, Horie K, Young LJ. Melanocortin agonism in a social context selectively activates nucleus accumbens in an oxytocin-dependent manner. Neuropharmacology. 2024;247:109848.
- Jain S, Panyutin A, Liu N, et al. Melanotan II causes hypothermia in mice by activation of mast cells and stimulation of histamine 1 receptors. American Journal of Physiology-Endocrinology and Metabolism. 2018;315(3):E357-E366.
- Wessells H, Levine N, Hadley ME, Dorr RT, Hruby VJ. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-646.
- Eliason NL, Martin L, Low MJ, Sharpe AL. Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food. Neuropeptides. 2022;96:102289.
- Minakova E, Lang J, Medel-Matus JS, et al. Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism. PLoS ONE. 2019;14(1):e0210389.
- Ter Laak MP, et al. Melanotan II promotes peripheral nerve regeneration in a rat sciatic nerve crush model. 2003.
- Evans-Brown M, Dawson RT, Chandler MD, McVeigh J. Use of melanotan I and II in the general population. BMJ. 2009;338:b566.
- Wu JC, Tsai HE, Hsiao YH, et al. Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition. International Journal of Molecular Sciences. 2020;21(2):681.
- Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Reports. 2019;12(2):e227644.
- Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clinical Toxicology. 2012;50(10):1169-1173.
- Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan II: a possible cause of renal infarction. CEN Case Reports. 2020;9(2):159-161.
- Sivyer GW. Dermatological changes with melanotan II use in a FAMMM patient. Dermatology Practical & Conceptual. 2012.
- Ryakhovsky VV, Khachiyan GA, Kosovova NF, et al. The first preparative solution phase synthesis of melanotan II. Beilstein Journal of Organic Chemistry. 2008;4:39.
- Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34-36.
- Giuliano F, Clement P, Droupy S, et al. Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience. 2006;138(1):293-301.
- Li G, Zhang Y, Wilsey JT, Scarpace PJ. Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats. Journal of Endocrinology. 2004;182(1):123-132.
- King SH, et al. Melanocortin Receptors, Melanotropic Peptides and Penile Erection. Current Topics in Medicinal Chemistry. 2007;7(11):1111-1119.
- Wessells H, Levine N, Hadley ME, Dorr RT, Hruby VJ. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. International Journal of Impotence Research. 2000;12(Suppl 4):S74-S79.
Related Research Questions
Want the complete research review?
View Full Melanotan 2 Research Page→FOR RESEARCH USE ONLY
This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.