PT-141 (Bremelanotide / Vyleesi): MC4R Agonist for Female Sexual Desire

FDA-approved as-needed subcutaneous peptide for pre-menopausal hypoactive sexual desire disorder.

✅ Approved

Full name
Bremelanotide (PT-141)
Class
Non-selective melanocortin receptor agonist (MC4R > MC3R)
Half-life
~2.7 hours
Route
Subcutaneous, as-needed
Brand names
Vyleesi (Palatin / AMAG)
Regulatory status
FDA-approved 2019 for pre-menopausal HSDD

What it is

PT-141 (bremelanotide) is a synthetic cyclic heptapeptide analogue of α-MSH developed from melanotan II as an anti-obesity agent, but clinically developed for female sexual desire after central arousal effects were observed in early trials.

How it works

Agonism at central MC4R (with partial activity at MC3R, MC1R) modulates hypothalamic circuits regulating sexual arousal. The mechanism is distinct from vascular-focused drugs like sildenafil — it acts on desire rather than erectile function.

PT-141 does not cause persistent elevation of sex hormones; effects are acute and related to each dose. As-needed use avoids chronic receptor desensitisation.

What the research shows

RECONNECT and RECONNECT-2 Phase 3 trials demonstrated efficacy.

Kingsberg SA et al. (2019) — RECONNECT Phase 3

Kingsberg S.A. et al., Obstet Gynecol 2019;134:899–908. 👥 Human studies

Two 24-week Phase 3 trials in 1,247 pre-menopausal women with HSDD randomised to bremelanotide 1.75 mg SC as-needed or placebo.

Significant improvement in sexual desire (FSFI-D) and decreased distress (FSDS-DAO) scores; nausea was the most common adverse event.

Limitations: Effect sizes modest; high nausea rate; not indicated for post-menopausal women.

Safarinejad MR (2008) — exploratory male erectile dysfunction

Safarinejad M.R., J Urol 2008;180:2041–2046. 👥 Human studies

Exploratory data in men with ED who had failed PDE5 inhibitors showed improved erectile function with intranasal bremelanotide.

Intranasal programme was halted due to blood-pressure elevations; SC route enabled the female indication.

Limitations: Not the approved indication; discontinued male programme.

Safety and limitations

Nausea (40%), flushing, headache, and transient blood-pressure elevation are common. Focal hyperpigmentation with repeated use reflects MC1R activity.

Contra-indicated in uncontrolled hypertension or known cardiovascular disease. Not for use more than 8 times per month.

Sources

  1. Kingsberg S.A. et al. Obstet Gynecol 2019;134:899–908. PubMed
  2. FDA Vyleesi Prescribing Information (2019). PubMed

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