Disclaimer: Information provided is for research and educational purposes only. Melanotan-II is not approved by the FDA or EMA for human or cosmetic use.

Introduction:

Melanotan-II (MT-II), often called the “tanning peptide,” is a synthetic analog of the natural α-melanocyte-stimulating hormone (α-MSH). It was developed in the 1980s to explore sunless tanning and skin-protection effects.¹ As a melanocortin receptor agonist, Melanotan-II promotes skin pigmentation and has been studied for its influence on sexual function, energy balance, and UV protection.¹ ² ³ ⁴ ⁸ ⁹

MT-II Fast Facts

• Class: Melanocortin receptor agonist (α-MSH analog)
  
• Design: Cyclic heptapeptide (lactam bridge) engineered for potency/stability
  
• Primary targets: MC1R (pigmentation), central MC3R/MC4R (sexual function, energy balance).⁸
  
• Most studied effects: Increased pigmentation; erectogenic response in ED cohorts; nausea/yawning common.¹

Melanotan-2 Chemical Structure

What exactly does MT-II do?

MT-II stimulates melanogenesis via MC1R on melanocytes → darker pigmentation following short subcutaneous dosing.¹

In the CNS, MT-II can trigger erections without sexual stimulation, pointing to central melanocortin circuitry (hypothalamic and spinal sites).²

Discovery & Research Milestones

• Originated at the University of Arizona in the 1980s, where researchers were exploring sunless tanning agents.¹
  
• Built as a short, stable analog of α-MSH, improving its half-life and activity compared to the natural hormone.²
  
• Early studies tested Melanotan II in skin pigmentation disorders and sexual dysfunction, but it never achieved regulatory approval.^³

Year	Study & Source	Key Finding
1996	Dorr RT et al.	Visible tanning after low-dose MT-II; common side effects include nausea & yawning. Recommended 0.025 mg/kg.
1998	Wessells H et al.	First studies on use for erectile dysfunction. MT-2 induces erections without erotic stimuli
2000-2003	Wessells H et al.	Mechanism established: central melanocortin pathways (hypothalamus and spinal cord) mediate MT-II-induced erection.
2003-2004	PT-141 program	MT-II signal translated into PT-141/bremelanotide; early RCTs show dose-dependent erectile activity and acceptable tolerance.

A Closer Look: What the Research Shows

• Skin Pigmentation (Tanning)
  A single-blind, alternating-day phase-I trial found visible tanning after five low doses and recommended 0.025 mg/kg for future studies; common AEs were nausea, yawning, somnolence.
• Erectile physiology
  A double-blind, placebo-controlled crossover study showed robust erections (average of 38 min of >80% rigidity) with 0.025 mg/kg MT-II; nausea/yawning increased vs. placebo.
• Development of PT-141
  The erectogenic signal from MT-II led to development of PT-141/bremelanotide (a related melanocortin agonist)

Research Applications

• Pigmentation disorders: Investigated for use in vitiligo and erythropoietic protoporphyria.²
  
• Skin protection: Studied for potential reduction of UV-related skin damage.³
  
• Sexual function: Explored as a treatment for erectile dysfunction and female sexual arousal disorder. ³

Regulatory Status

• MT-II: Not approved for tanning or sexual function
• Afamelanotide (MT-I) is approved for EPP (EU 2014; US 2019); long-term safety/PK are reviewed separately.

Summary

Melanotan-2 is a potent melanocortin agonist that darkens skin (via MC1R) and triggers erections by acting on central melanocortin pathways. Controlled early trials defined doses and common AEs; the erectogenic signal catalyzed development of bremelanotide.

FAQs About Melanotan II

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References

1. 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 Sci. 1996;58(20):1777-1784. https://pubmed.ncbi.nlm.nih.gov/8637402/
   
2. 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. J Urol. 1998;160(2):389-393. https://pubmed.ncbi.nlm.nih.gov/9679884/
   
3. Vemulapalli R, Kurosawa M, Killinger J, et al. Activation of central melanocortin receptors by melanotan-II (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂) results in penile erection in rats. Neuroscience. 2001;106(3):547-552. https://pubmed.ncbi.nlm.nih.gov/11591452/
   
4. Wessells H, Hruby V J, Hackett J, et al. Central melanocortin pathways mediate the erectogenic effects of melanotan-II in animal models. J Urol. 2003;170(6 Pt 1):S. (Abstract and mechanistic report.) https://pubmed.ncbi.nlm.nih.gov/14665870/
   
5. Rosen R C, Diamond L E, Earle D C, Shadiack A M, Molinoff P B. Evaluation of the safety, pharmacokinetics and pharmacodynamics of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with erectile dysfunction. J Sex Med. 2004;1(3):193-202. https://pubmed.ncbi.nlm.nih.gov/14999221/
   
6. Diamond L E, Earle D C, Garcia W D, Spana C. Double-blind, placebo-controlled evaluation of the safety, efficacy and dose response of subcutaneous PT-141 in men with erectile dysfunction. Int J Impot Res. 2004;16(4):353-360. https://pubmed.ncbi.nlm.nih.gov/14963471/
   
7. Hadley M E. Discovery that a melanocortin regulates sexual functions in male and female humans. Peptides. 2005;26(10):1687-1691. https://pubmed.ncbi.nlm.nih.gov/15996790/
   
8. Cai M, Hruby V J. Melanocortin receptors: their structure, function, and ligands. Peptides. 2016;88:3-18. https://pubmed.ncbi.nlm.nih.gov/27746082/ (Open access PMC article: https://pmc.ncbi.nlm.nih.gov/articles/PMC5999398/)
   
9. Mun Y, Jeon J H, Lee E S, et al. Melanocortin-1 receptor (MC1R): pharmacology and therapeutic prospects. Pharmaceutics. 2023;15(7):1814. https://pmc.ncbi.nlm.nih.gov/articles/PMC10418475/
   
10. Hjuler K F, Brøgger-Mikkelsen M, Pedersen S, et al. Melanoma associated with the use of melanotan-II. Acta Derm Venereol. 2014;94(1):115-116. https://pubmed.ncbi.nlm.nih.gov/24355990/
    
11. DermNet NZ. Melanotan II – Uses and side effects. (Clinical dermatology resource.) https://dermnetnz.org/topics/melanotan-ii
    
12. Minder E I, Schneider-Yaniv L, Schneider-Yaniv Z. Pharmacokinetics and pharmacodynamics of afamelanotide, a melanocortin 1 receptor agonist, in humans. Clin Pharmacokinet. 2017;56(8):815-826. https://pubmed.ncbi.nlm.nih.gov/28063031/