PT-141 (Bremelanotide)

What it is

Bremelanotide is a synthetic cyclic peptide analogue of alpha-melanocyte-stimulating hormone (α-MSH) that functions as a non-selective melanocortin receptor (MCR) agonist, with melanocortin type 4 receptor (MC4R) considered the most relevant subtype at therapeutic doses (PMIDs: 33455598, 31429064). MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus, an area important for female sexual function. Animal studies suggest bremelanotide may activate presynaptic MC4Rs on neurons in the mPOA, leading to increased release of dopamine, an excitatory neurotransmitter associated with increased sexual desire. Bremelanotide also activates melanocortin receptors 3 and 4 in glioblastoma cell lines, reducing survivin expression and inducing cell death in vitro. MC4R plays a central role in appetite regulation; agonist activity at this receptor promotes satiety. High-resolution structural studies have confirmed bremelanotide's binding mode at full-length MC4R in complex with heterotrimeric Gs protein. Earlier literature noted bremelanotide was also studied via intranasal route and proposed to act in the CNS to promote erections in preclinical models, and to stimulate behaviors facilitating sexual activity in both male and female models (PMIDs: 59584134, 18552829, 17983889).

Class: Melanocortin receptor agonist (synthetic cyclic peptide analogue of alpha-melanocyte-stimulating hormone [α-MSH])

What it's studied for

• Hypoactive Sexual Desire Disorder (HSDD) in premenopausal women Human RCT
  • Two identical Phase 3 randomized double-blind placebo-controlled multicenter trials (RECONNECT; n=1,247 safety population, n=1,202 efficacy population) of bremelanotide 1.75 mg subcutaneous as needed for 24 weeks in premenopausal women with HSDD. Statistically significant increases in sexual desire and reductions in di PMID 31599840 Kingsberg SA et al. Obstetrics and gynecology (2019)
  • 52-week open-label extension of RECONNECT (n=684 enrolled, n=272 completed). No new safety signals observed; sustained improvements in HSDD symptoms. Most common treatment-emergent adverse events: nausea (40.4%), flushing (20.6%), headache (12.0%). PMID 31599847 Simon JA et al. Obstetrics and gynecology (2019)
  • Phase 2b dose-finding RCT; n=327 premenopausal women. Bremelanotide 1.25/1.75 mg pooled vs. placebo: mean change in satisfying sexual events/month +0.7 vs. +0.2 (p=0.0180), FSFI total score +3.6 vs. +1.9 (p=0.0017), FSDS-DAO total score -11.1 vs. -6.8 (p=0.0014). Adverse events: nausea, flushing, headache. PMID 27181790 Clayton AH et al. Women's health (2016)
  • Review of bremelanotide safety from clinical development program (phases 1–3; 3,500 subjects, 43 completed studies). Most common AEs (double-blind phase 3): nausea (40.0% vs. 1.3% placebo), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), injection site reactions (5.4% vs. 0.5%). Focal hyperpigmentation rare with PMID 35147466 Clayton AH et al. Safety Profile of Bremelanotide. Journal of women's health (2022)
  • Prespecified and integrated subgroup analyses from RECONNECT (n=1,202). Bremelanotide achieved statistically significant improvements in desire and distress across age, weight, BMI, and baseline bioavailable testosterone subgroups, with few exceptions. Significant improvements also in patients with and without hormonal PMID 35230162 Simon JA et al. Journal of women's health (2022)
  • Re-analysis of Phase 3 bremelanotide trial data found 72.72% of protocol-listed outcomes were not reported; adverse event-induced discontinuation substantially higher on bremelanotide (OR=11.98; NNH: 6); participants preferred placebo over bremelanotide (OR=0.30; NNH: 4). Modest benefits on incompletely reported post-h PMID 33678061 Spielmans GI. Journal of sex research (2021)
  • Examination of Phase 3 RECONNECT efficacy measures found questionable validity evidence for primary outcomes (FSFI-D, FSDS-DAO item 13). 8 of 11 pre-specified outcomes were previously unpublished; effect sizes ranged from nil to small across all reported outcomes. PMID 36809187 Spielmans GI, Ellefson EM. Journal of sex research (2024)
  • RECONNECT exit surveys (n=242) and telephone interviews (n=80) found bremelanotide-treated patients reported increased feelings of sexual desire, physical arousal, and improvement in overall quality of sexual activities compared with placebo recipients. PMID 33538638 Koochaki P et al. Journal of women's health (2021)
  • Responder analyses from Phase 2b dose-ranging study. At 1.75 mg, responder rates achieved statistical significance vs. placebo (P≤0.03) across all 7 endpoints in the overall modified intention-to-treat population. PMID 31277966 Althof S et al. Journal of sexual medicine (2019)
• Female sexual dysfunction (desire, arousal, and orgasmic dysfunction) — broader populations Mixed
  • Systematic review and meta-analysis of 36 studies. Bremelanotide improved total FSFI and its desire and arousal subscales in women with FSD of desire, arousal, and/or orgasm (without pain). All three treatments (mindfulness-based CBT, flibanserin, bremelanotide) reduced distress. PMID 40543759 Toledo RG et al. Journal of minimally invasive gynecology (2026)
  • Narrative review of 30 systematic reviews and meta-analyses. Bremelanotide effective to improve desire, arousal, and orgasm scores. PMID 35147017 da Silva Lara LA et al. Minerva obstetrics and gynecology (2022)
  • Meta-analysis of 8 RCTs using FSFI as outcome. Women receiving placebo improved 3.62 on FSFI; treatment arm (including bremelanotide) increased 5.35. Approximately 67.7% of treatment effect accounted for by placebo, suggesting current FSD treatments are minimally superior to placebo overall. PMID 29995725 Weinberger JM et al. Obstetrics and gynecology (2018)
• Erectile dysfunction (ED) in men — CNS/melanocortinergic mechanism Animal studies only
  • Preclinical review: bremelanotide appears to act in the CNS to promote erections in preclinical models and may stimulate behaviors facilitating sexual activity beyond erectogenic effects. PMID 18552829 Shadiack AM et al. International journal of impotence research (2008)
  • Review noting bremelanotide (a melanocortin agonist) has been tested in men with ED and may prove to be one of the first centrally acting agents with clinical utility in male sexual dysfunction. PMID 18552830 Hellstrom WJG. International journal of impotence research (2008)
  • Review describing Phase II clinical trial data supporting melanocortin-based therapy (bremelanotide, then nasally administered) for erectile dysfunction. Noted as well tolerated and not associated with hypotension observed with PDE5 inhibitors. PMID 17584134 Shadiack AM, Sharma SD et al. Current topics in medicinal chemistry (2007)
  • Narrative review: PT-141 shows efficacy for ED through central nervous system activation and nitric oxide regulation; large-scale clinical trials needed to establish safety profiles, optimal dosing, and synergistic effects. PMID 40069591 Ila V et al. Expert opinion on pharmacotherapy (2025)
• Body weight reduction / caloric intake reduction in obese women Human RCT
  • Two Phase 1 randomized double-blind placebo-controlled trials in premenopausal obese women (BMI >30 kg/m²). Study A: bremelanotide (subcutaneous, three times daily for 15 days) produced significantly greater weight reduction vs. placebo (LS mean difference -1.3 kg; p<0.0001) and reduced caloric intake ~400 kcal/day. St PMID 35170192 Spana C et al. Diabetes, obesity & metabolism (2022)
• Glioblastoma — cell death induction and growth inhibition (in vitro) In vitro only
  • Bremelanotide reduced survivin expression and induced cell death in human glioblastoma cell lines at concentrations not toxic to normal human cells, via melanocortin receptors 3 and 4. Also promoted cell death induced by temozolomide and osimertinib in combination. PMID 39197897 Suzuki S et al. Anticancer research (2024)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

Safety signals

• Nausea: most common adverse event (40.0% bremelanotide vs. 1.3% placebo in Phase 3 double-blind integrated studies); most common reason for discontinuation PMID 35147466
• Flushing: 20.3% bremelanotide vs. 1.3% placebo in Phase 3 double-blind integrated studies PMID 35147466
• Headache: 11.3% bremelanotide vs. 1.9% placebo in Phase 3 double-blind integrated studies PMID 35147466
• Injection site reactions: 5.4% bremelanotide vs. 0.5% placebo in Phase 3 double-blind integrated studies PMID 35147466
• Focal hyperpigmentation: rare at label-recommended dosing, but occurred in >1/3 of subjects with up to 16 consecutive daily dosings PMID 35147466
• Small, transient but statistically significant blood pressure increases observed on ambulatory blood pressure monitoring; caution advised in patients at cardiovascular risk PMID 35147466
• Adverse event-induced study discontinuation substantially higher on bremelanotide vs. placebo: OR=11.98 (95% CI 3.74–38.37); NNH: 6 PMID 33678061
• Drug-drug interactions: bremelanotide lowered plasma concentrations of indomethacin and naltrexone (most other drug-drug interactions not clinically significant; no clinically significant interaction with ethanol) PMID 35147466
• Nausea was the only severe treatment-emergent adverse event experienced by more than one participant during the 52-week open-label extension; no deaths and few serious AEs across development program PMID 31599847
• Nausea (39.9%), facial flushing (20.4%), and headache (11%) reported in Phase 3 trials independently by Mayer and Lynch review PMID 31893927

Contraindications

• Caution advised in patients at risk of cardiovascular disease; blood pressure should be well controlled during treatment due to observed transient BP increases PMID 35147466
• Caution advised due to limited efficacy, potential adverse effects, and transparency issues in reporting; pharmacotherapy should be used within a multidisciplinary approach PMID 38767282
• Pregnancy and lactation: listed as subject headings in a drug review (Vyleesi for HSDD), indicating special populations of concern; no explicit contraindication text available from the abstract PMID 31381550