Overview

Melanotan-II is a synthetic cyclic analog of alpha-melanocyte stimulating hormone (α-MSH) developed at the University of Arizona in the 1980s as part of research into melanocortin receptor pharmacology. It acts as a non-selective agonist at MC1R, MC3R, MC4R, and MC5R, of which MC1R activation on melanocytes drives cutaneous pigmentation, and MC4R activation in the central nervous system is associated with the erectile and appetite-suppressant effects observed in early trials.

The MT-II programme was discontinued in favour of the MC4R-selective agonist bremelanotide (PT-141), which was later approved for a specific indication. MT-II itself remains a research reagent and is not an approved medicine.

Mechanism (as reported in the literature)

  • MC1R agonism. Research characterises MC1R activation on melanocytes as producing increased eumelanin synthesis and dermal pigmentation. Effects are more pronounced in individuals with functional MC1R alleles.
  • MC4R agonism. Studies indicate MC4R activation in hypothalamic circuits contributes to the appetite-suppressant and erectogenic effects reported in early clinical work.
  • MC5R and MC3R. Research on these receptors continues; effects on exocrine glands and inflammation are areas of ongoing study.

Research findings

  • Pigmentation studies. Early phase-1 and phase-2 investigator-initiated trials at the University of Arizona reported dose-dependent skin darkening in most subjects with reported doses of 250–500 mcg daily during induction (Dorr et al., 2000; PMID 10717326).
  • Sexual-function observations. Erectogenic effects were reported as a consistent adverse-event pattern in early trials, motivating the development of the MC4R-selective bremelanotide.
  • Appetite and body weight. Small studies reported reduced food intake during dosing.

Melanotan-II has never received regulatory approval and is characterised in the research literature only.

Common dosing (from published research protocols)

Induction protocols reported in the literature commonly began at 250 mcg daily, with dose adjustment based on reported tolerability and the rate of pigmentation change, up to approximately 1,000 mcg. Maintenance protocols reduced frequency to twice weekly once a target pigmentation was reached.

Reconstitution

A 10 mg vial reconstituted with 2 mL of bacteriostatic water yields a 5,000 mcg/mL solution. Under those conditions:

  • 250 mcg = 0.05 mL = 5 units on a U-100 syringe
  • 500 mcg = 0.10 mL = 10 units
  • 1,000 mcg = 0.20 mL = 20 units

Storage

Lyophilised MT-II is described as stable at ambient temperatures for shipping. Reconstituted solutions are refrigerated at 2–8 °C and reported as stable for approximately 30 days; longer storage is freezer-based.

  • PT-141 — the MC4R-selective successor to MT-II, developed for sexual-health research.
  • GHK-Cu — a distinct copper tripeptide studied in skin biology.

Common stacks

References

  • Dorr, R. T., et al. (2000). “Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.” Life Sciences, 66(23). PMID 10717326.
  • Hadley, M. E., Dorr, R. T. (2006). “Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.” Peptides, 27(4). PMID 16480791.
  • King, S. H., et al. (2007). “Melanocortin receptors, melanotropic peptides and penile erection.” Current Topics in Medicinal Chemistry, 7(11). PMID 17584134.