Bremelanotide

The Approved Drug Behind PT-141

Bremelanotide is the generic name for the compound most of the peptide community knows as PT-141, and since 2019 it has also been the approved active ingredient in Vyleesi, the first and only FDA-approved on-demand melanocortin therapy for hypoactive sexual desire disorder in premenopausal women. This page focuses on bremelanotide as a regulated drug — its label, its trial program, its pricing and access — rather than on the research-chemical PT-141 product sold by peptide vendors. For the community-use framing and the wider research history of the molecule, see our separate PT-141 page.

Structure and Mechanism

Bremelanotide is a cyclic heptapeptide (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH) derived from the alpha-MSH lineage by Palatin Technologies. Like its parent compound Melanotan II, it activates the melanocortin receptor family, but with a shift in selectivity away from MC1R (pigmentation) toward MC3R and MC4R — the receptors relevant to central nervous system control of sexual arousal. The hypothesized mechanism is not vascular but neural: MC4R activation in hypothalamic pathways modulates downstream dopaminergic signaling that contributes to subjective desire and arousal, distinct from the peripheral vasodilation produced by PDE5 inhibitors.

Clinical Development and the RECONNECT Program

Bremelanotide was developed through two pivotal Phase 3 trials — RECONNECT Study 301 and Study 302 — run by Palatin and AMAG Pharmaceuticals between 2014 and 2016. The trials enrolled approximately 1,200 premenopausal women with acquired, generalized HSDD and randomized them to on-demand subcutaneous bremelanotide 1.75 mg versus placebo. Co-primary endpoints were change in the Female Sexual Function Index desire domain and change in the Female Sexual Distress Scale item 13.

• Both trials met their co-primary endpoints with statistical significance.
• Effect sizes were modest — roughly 0.3–0.5 points on the FSFI desire domain versus placebo.
• The most common adverse events were nausea (about 40% of treated patients, driving a meaningful discontinuation rate), flushing, headache, and injection-site reactions.
• A small subset of patients experienced transient increases in blood pressure and decreases in heart rate, which shaped the eventual label.

On the basis of these results the FDA approved bremelanotide (Vyleesi) on June 21, 2019 for acquired, generalized HSDD in premenopausal women — the same indication for which Addyi (flibanserin) had been approved in 2015, but with a radically different mechanism and on-demand rather than daily dosing.

The Approved Label in Practice

The Vyleesi label specifies on-demand subcutaneous self-injection of a single 1.75 mg auto-injector 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. Key label restrictions include:

• Cardiovascular contraindication. Uncontrolled hypertension or known cardiovascular disease are listed contraindications because of the transient BP elevation seen in trials.
• Concomitant oral naltrexone. Bremelanotide can reduce naltrexone exposure enough to risk opioid-use-disorder treatment failure, and this is a contraindication.
• Focal hyperpigmentation. With repeated use — especially in patients with darker skin or those receiving more than eight doses per month — focal hyperpigmentation of the face, gums, or breasts has been reported.

Access, Pricing, and Commercial Trajectory

Vyleesi has had a commercially difficult run. AMAG divested the product back to Palatin in 2020 after slow uptake, and Palatin has continued to market it directly. Cash pricing is typically several hundred dollars per dose without insurance coverage, and payer coverage has been uneven — much of the market has turned instead to compounded bremelanotide, which lives in a different regulatory space and closer to the research-chemical supply chain discussed on the PT-141 page.

Honest Framing

Bremelanotide is the rare peptide in this library that has actually been through Phase 3 trials and received FDA approval. The approved clinical effect is real but modest, the tolerability profile is a meaningful constraint, and commercial adoption has been limited. As a regulated drug with a defined label, Vyleesi is a categorically different product from compounded or research-chemical bremelanotide — that distinction is where the practical and safety implications live.