PT-141 (Bremelanotide)

What Is PT-141?

PT-141 (bremelanotide) is a synthetic cyclic heptapeptide and active metabolite of Melanotan II. FDA-approved in 2019 as Vyleesi™ for premenopausal HSDD — the first and only approved sexual dysfunction treatment to act centrally via melanocortin receptors rather than peripherally via vascular mechanisms.

Key Mechanisms

• MC4R agonism (PVN) — triggers dopamine release in NAc; initiates central sexual arousal
• MC3R agonism (ARC) — sexual motivation via mesolimbic dopamine pathway
• Spinal pro-erectile centres — MC4R in thoracolumbar cord; effective in PDE5 non-responders
• Endogenous oxytocin release — PVN MC4R activation stimulates OT neurons — pharmacological OTR synergy

Key References

1. Kingsberg SA et al. “Bremelanotide for HSDD.” Obstet Gynecol, 2019;134(5):899–908.
2. Shadiack AM et al. “Melanocortins in treatment of male and female sexual dysfunction.” Curr Top Med Chem, 2007;7:1137–1144.