💊PT-141 (Bremelanotide)
FDA-approved (Vyleesi, 2019) CNS melanocortin receptor agonist. Acts via MC3R/MC4R in hypothalamus — not peripherally. Effective in PDE5 non-responders.
Cyclic heptapeptide α-MSH analogueWhat 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
- Kingsberg SA et al. "Bremelanotide for HSDD." Obstet Gynecol, 2019;134(5):899–908.
- Shadiack AM et al. "Melanocortins in treatment of male and female sexual dysfunction." Curr Top Med Chem, 2007;7:1137–1144.
Frequently Asked Questions
PDE5 inhibitors act peripherally on vascular smooth muscle to support blood flow; PT-141 acts centrally on melanocortin receptors (MC3R/MC4R) in the hypothalamus and spinal cord to influence the neurological arousal pathway itself — which is why it's studied specifically in populations that don't respond to PDE5 inhibitors.
No — PT-141 (bremelanotide) is a metabolite of Melanotan II, produced by removing the C-terminal amide group. It shares the melanocortin mechanism but has a distinct receptor-selectivity profile and is the form that received FDA approval (as Vyleesi) in 2019.
Vyleesi (bremelanotide) received FDA approval in 2019 for premenopausal hypoactive sexual desire disorder (HSDD) — one of the few peptides in this wiki with a completed approval pathway.