Overview

PT-141 (bremelanotide) is a cyclic melanocortin agonist derived from the same University of Arizona research programme that produced melanotan-II. Unlike MT-II, PT-141 lacks the C-terminal amide and shows a receptor preference favouring MC4R over MC1R, which reduces cutaneous pigmentation effects while preserving the central-nervous-system sexual-arousal effects observed with the parent scaffold.

Bremelanotide received FDA approval in 2019 under the brand name Vyleesi for a specific indication in premenopausal women. That approval is the reference source for much of the published pharmacokinetic and safety data.

Mechanism (as reported in the literature)

  • MC4R agonism in central pathways. Research characterises MC4R activation in hypothalamic and limbic circuits as producing pro-sexual effects independent of the peripheral vascular pathway targeted by phosphodiesterase-5 inhibitors.
  • Nitric-oxide-independent action. Studies indicate the mechanism is upstream of the peripheral NO/cGMP pathway that drives sildenafil-class effects, which explains observations of activity in models refractory to PDE5 inhibitors.
  • Blood-pressure sensitivity. Trial reports and animal studies describe transient blood-pressure elevation attributed to melanocortin-receptor signalling in autonomic control regions.

Research findings

  • Female sexual dysfunction trials. The RECONNECT phase-3 trials in premenopausal women with hypoactive sexual desire disorder reported improvements versus placebo on desire and distress domain scores at a 1.75 mg subcutaneous dose (Kingsberg et al., 2019, Obstet Gynecol; PMID 31135723).
  • Male erectile-function studies. Earlier subcutaneous- and intranasal-formulation trials reported improvements in erectile-function scores, including in cohorts with a suboptimal response to sildenafil (Rosen et al., 2004; Diamond et al., 2004).
  • Cardiovascular and blood-pressure findings. The intranasal programme in men was ended in part due to transient blood-pressure elevation observations; the approved subcutaneous formulation carries a related labelling advisory.

Common dosing (from published research protocols)

The reference clinical dose is 1.75 mg subcutaneously, self-administered at least 45 minutes before anticipated sexual activity, with a maximum of one dose per 24 hours and no more than eight doses per month. Research protocols in earlier studies used doses of 1–2 mg.

Reconstitution

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

  • 1,000 mcg = 0.20 mL = 20 units on a U-100 syringe
  • 1,750 mcg = 0.35 mL = 35 units
  • 2,000 mcg = 0.40 mL = 40 units

Storage

Lyophilised PT-141 is described as stable at ambient temperatures for shipping. Reconstituted solutions are refrigerated at 2–8 °C and used within approximately 30 days.

  • Melanotan-II — the non-selective melanocortin precursor.

Common stacks

References

  • Kingsberg, S. A., et al. (2019). “Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials.” Obstetrics & Gynecology, 134(5). PMID 31135723.
  • Rosen, R. C., et al. (2004). “Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141.” International Journal of Impotence Research, 16(2). PMID 14999221.
  • Molinoff, P. B., et al. (2003). “PT-141: a melanocortin agonist for the treatment of sexual dysfunction.” Annals of the New York Academy of Sciences, 994. PMID 12851297.