PT-141
Human RCTBremelanotide · Vyleesi · PT141 · Bremelanotide acetate
Highest available evidence among curated papers: Human RCT (as of 2026-06-04).
Chemical & identity
- Molecular formula
- C50H68N14O10
- Molecular weight
- 1025.2 g/mol · PubChem
- PubChem CID
- 9941379 · PubChem
- SMILES
- CCCC[C@@H](C(=O)N[C@H]1CC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC1=O)CC2=CN=CN2)CC3=CC=CC=C3)CCCN=C(N)N)CC4=CNC5=CC=CC=C54)C(=O)O)NC(=O)C
- InChIKey
- FFHBJDQSGDNCIV-MFVUMRCOSA-N
- ChEMBL ID
- CHEMBL2070241 · ChEMBL
- Category
- Melanocortin
Chemical/structural fields are auto-pulled and source-linked. ChEMBL data: ChEMBL_36, CC BY-SA 3.0.
Mechanism (curated)
Cyclic melanocortin receptor agonist (activates MC4R, with MC1R activity); the central MC4R action mediates its effect on sexual desire.
Pharmacology & handling
- Half-life
- Approximately 2–3 hours; administered subcutaneously on demand.
Research
Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent.
Human trialMintzes B, Tiefer L, Cosgrove L · Drug and therapeutics bulletin · 2021 · Narrative review
This narrative review examines the FDA approvals of flibanserin (2015) and bremelanotide (2019) for hypoactive sexual desire disorder in women. The authors report that in clinical trials, flibanserin produced only one additional enjoyable sexual experience every two months on average, while bremelanotide showed no such benefit. The review notes that both trials involved shifts in primary outcomes and a contested indication, and suggests that industry-sponsored advocacy and conflicted testimony influenced flibanserin's approval, with bremelanotide's approval following on regulatory precedent despite weaker efficacy data.
Bremelanotide: First Approval.
Human trialDhillon S, Keam SJ · Drugs · 2019 · Narrative review
Bremelanotide (Vyleesi™) is a melanocortin receptor agonist approved in the USA for treating hypoactive sexual desire disorder (HSDD) in premenopausal women. It is a synthetic peptide analogue of alpha melanocyte-stimulating hormone (α-MSH) with high affinity for the melanocortin type 4 receptor and is administered as a self-administered, on-demand subcutaneous therapy. The abstract describes this as a narrative review summarizing the development milestones and regulatory approval of bremelanotide, with Phase 3 clinical trials conducted by Palatin Technologies.
Borland JM et al. · Neuropharmacology · 2025 · Animal study
This is an animal study investigating the neurobiological mechanism of bremelanotide (Vyleesi), an FDA-approved peptide treatment for female hypoactive sexual desire disorder, using a female Syrian hamster model. Researchers examined melanocortin receptor expression in the mesolimbic dopamine system and found MC4R mRNA primarily in dopamine neurons of the ventral tegmental area, with less expression in the nucleus accumbens and dorsal striatum. Bremelanotide treatment at both low and high doses did not affect melanocortin receptor mRNA expression in these brain regions, and failed to enhance sexual reward as measured by conditioned place preference testing. The authors conclude that bremelanotide does not act on the VTA-NAc reward circuit and does not enhance sexual reward, though they discuss the findings in relation to similar rat studies.
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials.
Human RCTKingsberg SA et al. · Obstetrics and gynecology · 2019 · RCT
Two identical phase 3 randomized controlled trials (RECONNECT studies 301 and 302) evaluated bremelanotide 1.75 mg administered subcutaneously as needed in 1,267 premenopausal women with hypoactive sexual desire disorder. Over 24 weeks, bremelanotide significantly improved sexual desire and reduced distress related to low sexual desire compared to placebo in both studies. The most common adverse events were nausea, flushing, and headache (≥10%), which were mostly mild to moderate in intensity. The authors concluded that bremelanotide demonstrated significant efficacy with a favorable safety profile.
Simon JA et al. · Obstetrics and gynecology · 2019 · Other
This study presents the 52-week open-label extension phase of RECONNECT, which consisted of two parallel phase 3 trials (studies 301 and 302) evaluating bremelanotide for hypoactive sexual desire disorder in premenopausal women. Of 856 patients who completed the 24-week double-blind core phase, 684 enrolled in the open-label extension and 272 completed it. The most common treatment-emergent adverse events related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), with no new safety signals observed during the extension. Patients who received bremelanotide during the core phase showed sustained improvements in Female Sexual Function Index-desire domain scores and Female Sexual Distress Scale scores compared to those who had received placebo.
Spana C, Jordan R, Fischkoff S · Diabetes, obesity & metabolism · 2022 · RCT
Two phase 1 randomized controlled trials examined bremelanotide, an MC4R agonist, in premenopausal obese women. Study A (n=30) gave subcutaneous bremelanotide or placebo three times daily for 15 days; bremelanotide subjects showed significantly greater body weight reduction (−1.3 kg vs. placebo, p<0.0001) and ~400 kcal/day lower caloric intake (p<0.01). Study B (n=27) used a crossover design with once- or twice-daily dosing; twice-daily bremelanotide produced greater weight loss (1.7 vs. 0.9 kg, p<0.001) and 398–469 kcal greater caloric reduction versus placebo (p<0.0001). The authors conclude that MC4R agonism may aid weight loss and caloric reduction in obese women.
Clayton AH et al. · Women's health (London, England) · 2016 · RCT
This randomized, placebo-controlled dose-finding trial evaluated bremelanotide (BMT), a melanocortin-receptor-4 agonist, in 327 premenopausal women with female sexual dysfunctions. Participants received self-administered subcutaneous injections of placebo or BMT (0.75, 1.25, or 1.75 mg) as desired over 12 weeks. The pooled 1.25/1.75-mg dose showed statistically significant improvements versus placebo in satisfying sexual events per month (+0.7 vs +0.2), female sexual function index scores (+3.6 vs +1.9), and female sexual distress scale scores (−11.1 vs −6.8). Adverse events included nausea, flushing, and headache; the study concluded BMT was safe, effective, and well tolerated.
Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide.
Human RCTSimon JA et al. · Journal of women's health (2002) · 2022 · RCT
This report presents prespecified subgroup analyses from the RECONNECT phase 3 studies, two identically designed double-blind randomized placebo-controlled trials of bremelanotide (a melanocortin receptor agonist) versus placebo for hypoactive sexual desire disorder (HSDD) in premenopausal women. Among 1202 patients, bremelanotide 1.75 mg administered subcutaneously as needed achieved statistically significant improvements in sexual desire and decreased distress across subgroups defined by age, weight, BMI, and bioavailable testosterone levels, with few exceptions. Improvements were observed regardless of hormonal contraceptive use and HSDD duration. The study concluded that bremelanotide showed statistically significant improvements in sexual desire and reduced distress across several prespecified subgroups.
Clayton AH et al. · Journal of women's health (2002) · 2022 · Narrative review
This systematic review of bremelanotide's clinical development program analyzed safety data from 3500 subjects across 43 completed studies (phases 1–3), including up to 18 months of treatment in phase 3. The most common adverse events were nausea (40.0% vs. 1.3% placebo), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), and injection site reactions (5.4% vs. 0.5%), with nausea being the primary reason for discontinuation. Focal hyperpigmentation was rare with label-recommended dosing but occurred in over one-third of subjects after up to 16 consecutive daily doses; small, transient blood pressure increases were observed. Most drug–drug interactions were not clinically significant, except for interactions affecting indomethacin and naltrexone plasma concentrations.
Diamond LE et al. · The journal of sexual medicine · 2006 · RCT
This randomized, double-blind, crossover study evaluated a single intranasal dose of bremelanotide (PT-141), a melanocortin receptor agonist peptide, in 18 premenopausal women with sexual arousal disorder. More women reported moderate or high sexual desire after bremelanotide than placebo (P = 0.0114), and among those who attempted intercourse within 24 hours, more were satisfied with their arousal level after bremelanotide (P = 0.0256). A trend toward increased genital arousal feelings was noted with bremelanotide (P = 0.0833), but vaginal vasocongestion measured during erotic videos did not differ significantly between bremelanotide and placebo. The authors conclude bremelanotide shows promise for further evaluation in women with sexual arousal disorder.
Diamond LE et al. · International journal of impotence research · 2004 · RCT
PT-141, a cyclic heptapeptide melanocortin analog, was evaluated in a double-blind, placebo-controlled study following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Pharmacokinetic analysis showed dose-dependent increases in C(max) and AUC, with median T(max) of 0.50 h and mean half-life of 1.85–2.09 h. PT-141 induced statistically significant erectile response compared to placebo at doses greater than 7 mg, with first erection onset in approximately 30 minutes. PT-141 was well tolerated, with flushing and nausea as the most common adverse events, no maximum-tolerated dose identified, and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical examinations.
Diamond LE et al. · Urology · 2005 · RCT
This randomized cross-over study in 19 men with erectile dysfunction evaluated co-administration of low-dose intranasal PT-141 (7.5 mg), a melanocortin receptor agonist cyclic heptapeptide, with sildenafil (25 mg) versus sildenafil alone or placebo. Erectile response was assessed by RigiScan during visual sexual stimulation over 6 hours. PT-141 combined with sildenafil produced a significantly greater erectile response than sildenafil alone and was safe and well-tolerated with no new or increased adverse events.
Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder.
Human trialSpielmans GI, Ellefson EM · Journal of sex research · 2024 · Narrative review
This narrative review examines the measurement properties of efficacy outcomes from phase III bremelanotide trials (RECONNECT) for hypoactive sexual desire disorder in women. The authors found that continuous efficacy measures including the Female Sexual Function Index and Female Sexual Distress Scale-Desire/Arousal/Orgasm had questionable validity evidence for HSDD. Eight of eleven clinicaltrials.gov-specified efficacy outcomes were previously unpublished, and when analyzed showed effect sizes ranging from nil to small. The authors conclude that bremelanotide's benefits are statistically modest and limited largely to outcomes with scant validity evidence in women with HSDD.
Pfaus J, Giuliano F, Gelez H · The journal of sexual medicine · 2007 · Animal study
Bremelanotide, an alpha-MSH analogue, was tested in ovariectomized, hormone-primed female rats using a model allowing the animals to control timing of sexual encounters. The peptide dramatically increased solicitation (appetitive sexual behavior) following subcutaneous injection or direct infusion into the lateral ventricles or medial preoptic area (mPOA), but not the ventromedial hypothalamus, without altering pacing or lordosis. Peripheral administration activated the mPOA and other hypothalamic and limbic regions, possibly via dopamine terminals in the mPOA. The authors conclude bremelanotide shows behavioral, pharmacological, and neuroanatomical specificity consistent with potential treatment of hypoactive sexual desire disorder in females.
Molinoff PB et al. · Annals of the New York Academy of Sciences · 2003 · Other
PT-141 is a synthetic peptide analogue of alpha-MSH that acts as an agonist at melanocortin receptors (MC3R and MC4R) expressed in the central nervous system. In animal studies, PT-141 administration to rats and nonhuman primates induced penile erections, and in rats it activated hypothalamic neurons as measured by c-Fos immunoreactivity. In humans, PT-141 administration to both normal men and patients with erectile dysfunction produced rapid, dose-dependent increases in erectile activity. The findings suggest PT-141 may be a promising treatment for sexual dysfunction.
Summaries are our own; we link to originals (PubMed / DOI) and never rehost full text.
Regulatory status
- FDA approved
- Yes
- WADA prohibited
- No
- Compounding status
- FDA-approved (Vyleesi) for hypoactive sexual desire disorder (HSDD) in premenopausal women.
- Notes
- FDA-approved bremelanotide (Vyleesi) for acquired, generalized HSDD in premenopausal women as of 2026-06-04. Not listed on the WADA prohibited list. Note: trial efficacy is statistically significant but modest/debated (see curated critical reviews).
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04