PT-141 (Bremelanotide)
Bremelanotide acetate (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH)
An FDA-approved cyclic melanocortin receptor agonist indicated for hypoactive sexual desire disorder (HSDD) in premenopausal women. Marketed as Vyleesi by Cosette Pharmaceuticals. Administered as an on-demand subcutaneous injection. Acts centrally via brain melanocortin receptors rather than peripheral vasculature.
Last updated: 2026-03-12
Safety Summary
Nausea is the primary dose-limiting adverse event (~40%) and the main reason for discontinuation (~8%). The incidence and severity of nausea tend to decrease with subsequent doses. Hemodynamic effects (transient BP increase, HR decrease) are the basis for contraindication in uncontrolled hypertension and cardiovascular disease. Focal hyperpigmentation risk is strongly dose-frequency dependent: rare with labeled intermittent use (-��8 doses/month) but substantial with daily dosing (~38% in research settings). May persist after discontinuation and may be irreversible, particularly in darker skin. No evidence of tolerance or tachyphylaxis over 52 weeks of intermittent use in the clinical program. No withdrawal syndrome documented. No cancer signal in clinical program (~3,500 subjects) or FAERS data through mid-2025. No clinically significant anti-drug antibody formation. Transient ACTH/cortisol increases observed but not clinically significant at approved doses.
Known Side Effects
Very common (~40%)
Very common (~20-21%)
Very common (~11-12%)
Common (~4-6%)
Common (>4%)
Common (2-4%)
Common (2-4%)
Common (>2%)
Common (dose-related)
Common
Uncommon (~1% with labeled intermittent dosing; up to ~38% with daily dosing)
Rare (single case report of acute hepatitis)
Who Should NOT Use This
Transient BP increases (up to ~6 mmHg systolic) could be clinically significant in uncontrolled hypertension.
Transient hemodynamic effects (BP increase, HR decrease); safety not established in CVD patients.
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Bremelanotide slows GI transit and can significantly decrease systemic exposure of oral naltrexone, potentially leading to treatment failure.
No human data; potential fetal risk.
Rare hepatotoxicity signal (single case report). Limited data.
MC1R activation stimulates melanogenesis; theoretical concern about melanocyte activation. No clinical signal but monitoring recommended.
Talk to Your Doctor
Before considering PT-141 (Bremelanotide), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-5]
Evidence Assessment
FDA-approved drug (Vyleesi, NDA 210557, approved June 21, 2019) for HSDD in premenopausal women. Supported by two identical Phase 3 RECONNECT RCTs (integrated n=1,267) and 52-week open-label extension safety data. Development program included ~3,500 subjects across 43 studies. Active Phase 2 programs for ED, obesity, and diabetic nephropathy.
1Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials (RECONNECT)NCT01382719 / NCT02338960PMID 31599840
Kingsberg SA, Clayton AH, Portman D, et al. - Obstetrics & Gynecology (2019) - Two identical Phase 3 RCTs (integrated analysis) - 1267
Integrated: FSFI desire domain LS mean improvement +0.35 vs placebo (P<0.001); FSDS-DAO Item 13 LS mean reduction -0.33 vs placebo (P<0.001). Both coprimary endpoints met.
Limitations: Effect sizes small-to-moderate. 24-week treatment duration. Premenopausal women only. Industry-sponsored. High nausea rates.
2Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire DisorderPMID 31582365
Simon JA, Kingsberg SA, Portman D, et al. - The Journal of Sexual Medicine (2019) - 52-week open-label extension - 684
Efficacy maintained over 52 weeks. No evidence of tachyphylaxis or withdrawal. No new safety signals. Most common AEs: nausea (~40%), flushing (~20%), headache (~12%). Nausea severity decreased over time.
Limitations: Open-label design; no placebo comparator. Self-selected from parent RCTs.
3Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141 in healthy male subjects and in patients with an inadequate response to ViagraPMID 14999221
Rosen RC, Diamond LE, Earle DC, et al. - Int J Impot Res (2004) - Phase 1/2 (SC in men)
SC PT-141 induced erections in healthy males and men with ED who had inadequate response to sildenafil. Dose-dependent effect. PK: t½ ~2.7h, Tmax ~1h. Well-tolerated.
Limitations: Small sample. Early-stage. No large confirmatory RCT for male ED published.
4Phase 2 Clinical Study of Bremelanotide Co-Administered with PDE5i for ED
Palatin Technologies - Press release / ClinicalTrials.gov (2024) - Phase 2 (ongoing) - 50
Study initiated; safety results reported as positive per sponsor. No peer-reviewed efficacy data yet.
Limitations: Ongoing; open-label; small sample; no peer-reviewed publication.
5Phase 2 Obesity Study: Bremelanotide (MC4R agonist) and Tirzepatide CombinationNCT06565611
Palatin Technologies - ClinicalTrials.gov (2024) - Phase 2 (combination obesity study)
Palatin reported positive appetite suppression results from combination study.
Limitations: No peer-reviewed publication; small sample; early-stage.