PT-141 (Bremelanotide)

Also known as: Bremelanotide, Vyleesi

**Mechanism of Action** PT-141 (bremelanotide) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH) that acts as a selective agonist at melanocortin receptors, primarily MC4R and to a lesser extent MC1R and MC3R. Its central mechanism involves activation of MC4R in hypothalamic and limbic regions, modulating dopaminergic and oxytocinergic pathways to enhance sexual arousal and desire. Unlike PDE5 inhibitors, PT-141 does not rely on nitric oxide or vascular mechanisms, instead directly targeting central neural circuits governing sexual motivation. **Key Research Findings** Clinical trials (e.g., RECONNECT studies) demonstrated significant improvements in sexual desire and distress scores in premenopausal women with hypoactive sexual desire disorder (HSDD) compared to placebo. Common adverse effects include nausea (40%), flushing, and headache, with transient blood pressure elevation observed. Preclinical studies also show potential for erectile dysfunction treatment in men, though FDA approval is limited to HSDD. Pharmacokinetics reveal a Tmax of ~1 hour and half-life of 2–3 hours, with subcutaneous administration. **Clinical Relevance** Approved as Vyleesi (2019) for acquired, generalized HSDD in premenopausal women, PT-141 offers an alternative to flibanserin with a distinct mechanism and on-demand dosing (45 minutes before anticipated sexual activity). Its use is contraindicated with uncontrolled hypertension or cardiovascular disease due to pressor effects. Ongoing research explores applications in sexual dysfunction across genders and conditions like anorgasmia. For research purposes only — not medical advice.

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