PT-141
Published research and evidence base
Bremelanotide (PT-141) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that acts as a non-selective agonist at melanocortin receptors, with activity at MC4R in central nervous system pathways considered central to its effects on sexual response. It was first investigated as an intranasal agent for erectile dysfunction before being redeveloped as a subcutaneous on-demand injection, and was approved by the FDA in 2019 as Vyleesi for generalised acquired hypoactive sexual desire disorder in premenopausal women. The pivotal RECONNECT phase 3 programme and its open-label extension reported statistically significant but small improvements in desire and reductions in distress, alongside high rates of nausea, flushing and headache. Independent re-analyses and subsequent systematic reviews have debated the clinical magnitude of the effect, and use in men remains investigational.
- Studies cited
- 15
- Published 2023+
- 10
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- Melanocortin receptor (MC3R/MC4R) agonism as a central rather than vascular mechanism of sexual response
- Hypoactive sexual desire disorder in premenopausal women: FDA-approved indication
- Small effect sizes and contested clinical meaningfulness in independent re-analyses
- Characteristic tolerability profile: nausea, flushing, headache, transient blood pressure elevation, focal hyperpigmentation with frequent dosing
- Historic intranasal erectile dysfunction development and renewed interest in male sexual dysfunction
- Preclinical and in-vitro exploration of melanocortin agonism beyond sexual medicine
Compound identifiers
- CAS
- 189691-06-3
- PubChem
- 9941379
What PT-141 is, chemically.
- Molecular formula
- C50H68N14O10
- Molecular weight
- 1025.2 g/mol
- CAS number
- 189691-06-3
- PubChem CID
- 9941379
Bremelanotide
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Systematic review2026
Clinical trial evidence on emerging pharmacological therapies for hypoactive sexual desire disorder in women: a systematic review and analysis of completed studies registered on ClinicalTrials.gov
Ashour AM, et al. · Frontiers in Medicine · PRISMA-guided systematic review of nine completed registered pharmacological trials for HSDD in adult women
Flibanserin and bremelanotide were the most extensively studied agents, both acting on central nervous system pathways, and were most often evaluated in phase II/III randomised double-blind placebo-controlled designs in premenopausal women. Endpoint definitions and safety reporting varied substantially between trials, limiting cross-study comparison.
- 02Systematic review2026
Female Sexual Desire, Arousal, and Orgasmic Dysfunctions: A Systematic Review and Meta-Analysis of Treatment Options
Toledo RG, et al. · Journal of Minimally Invasive Gynecology · systematic review and meta-analysis, 8994 abstracts screened, 36 included studies (26 randomised controlled trials, 10 single-arm)
Pooled analysis found that bremelanotide improved desire and arousal outcomes and reduced sexual distress, alongside similar distress reductions for mindfulness-based cognitive behavioural therapy and flibanserin. The authors noted that conclusions for many other interventions could not be drawn because of limited study numbers and heterogeneous outcome measures.
- 03Systematic review2024
Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder
Spielmans GI · Journal of Sex Research · independent re-analysis of the phase 3 bremelanotide trial data and outcome measures
The re-analysis reported effect sizes ranging from nil to small across efficacy measures and questioned the validity evidence for several outcome instruments used. The author concluded that most favourable reported outcomes appeared to have been derived post hoc.
- 04Human clinical2022
Safety Profile of Bremelanotide Across the Clinical Development Program
Clayton AH, et al. · Journal of Women's Health · integrated safety analysis across 43 phase 1-3 studies, approximately 3500 subjects, dosing up to 18 months
Pooled analysis reported nausea (40.0% vs 1.3%), flushing (20.3% vs 1.3%) and headache (11.3% vs 1.9%) for bremelanotide versus placebo, with no deaths attributed to treatment. Focal hyperpigmentation occurred in more than a third of subjects exposed to consecutive daily dosing, a regimen outside the approved on-demand use.
- 05Human clinical2019
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials
Kingsberg SA, et al. · Obstetrics and Gynecology · two identical randomised double-blind placebo-controlled phase 3 trials (RECONNECT), 1267 premenopausal women with HSDD, subcutaneous bremelanotide 1.75 mg as needed, 24 weeks
Bremelanotide produced statistically significant improvements versus placebo in the desire domain score (0.30-0.42, p<.001) and reductions in the desire-related distress score (-0.29 to -0.37, p<=.005). Nausea, flushing and headache were each reported by at least 10% of treated participants.
- 06Human clinical2019
Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder
Simon JA, et al. · Obstetrics and Gynecology · 52-week open-label extension of the RECONNECT phase 3 trials, 684 enrolled of 856 eligible completers, 272 completed the extension
Treatment-emergent adverse events during open-label use were nausea (40.4%), flushing (20.6%) and headache (12.0%). Improvements in desire and reductions in distress observed in the core trials were maintained over the extension period.
- 07Human clinical2006
An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist
Diamond LE, et al. · The Journal of Sexual Medicine · randomised placebo-controlled crossover laboratory study, 18 premenopausal women with female sexual arousal disorder, intranasal bremelanotide 20 mg, counterbalanced sessions with neutral and erotic video
More women reported moderate or high sexual desire after bremelanotide than after placebo (p=0.0114). Among those who attempted intercourse within 24 hours of dosing, a greater proportion reported satisfaction with arousal after bremelanotide (p=0.0256).
- 08Human clinical2004
Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction
Diamond LE, et al. · International Journal of Impotence Research · double-blind placebo-controlled dose-escalation study of intranasal PT-141 in healthy men and men with mild-to-moderate erectile dysfunction, with RigiScan penile rigidity monitoring
Intranasal PT-141 showed dose-proportional pharmacokinetics with a median Tmax of 0.50 hours and a terminal half-life of approximately 1.85-2.09 hours. Erectile responses were recorded at doses above 7 mg within roughly 30 minutes of dosing; flushing and nausea were the most common adverse events and no maximum tolerated dose was reached.
- 09Animal in vivo2025
Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder
Borland JM, et al. · Neuropharmacology · female Syrian hamsters, receptor mRNA expression analysis plus low- and high-dose bremelanotide in a conditioned sexual reward paradigm
Melanocortin 3 and 4 receptor mRNA was localised predominantly to ventral tegmental area dopamine neurons. Neither dose of bremelanotide altered receptor expression or conditioned sexual reward in this species, and the authors concluded the drug did not enhance mesolimbic reward circuitry in this model. These are animal findings and do not describe human responses.
- 10In vitro2026
Goldilocks-Inspired Design of Mid-Size Macrocycles for Selective Targeting of Human Melanocortin Receptors
Merlino F, et al. · Journal of Medicinal Chemistry · synthesis and receptor pharmacology of 14 mid-size macrocyclic peptide analogues at human melanocortin receptor subtypes
Compounds FM648 and FM636 were characterised as potent and selective human MC4R antagonists, while FM635 acted as a selective MC4R agonist. The work illustrates ongoing structure-activity optimisation of melanocortin-targeting macrocycles beyond bremelanotide.
- 11In vitro2024
Melanocortin Receptor Agonist Bremelanotide Induces Cell Death and Growth Inhibition in Glioblastoma Cells via Suppression of Survivin Expression
Suzuki S, et al. · Anticancer Research · human glioblastoma cell lines treated with bremelanotide, with melanocortin receptor antagonists and forced survivin overexpression as controls
Bremelanotide reduced survivin expression and induced cell death in glioblastoma cell lines at concentrations non-toxic to control cells, an effect blocked by melanocortin receptor antagonists and by survivin overexpression. This is a cell-culture observation unrelated to any approved clinical indication.
- 12Review2026
Should Bremelanotide Be Considered for the Treatment of Sexual Arousal and Desire Disorders in Men?
Pfaus JG, et al. · Journal of Clinical Psychopharmacology · narrative commentary reviewing rodent preclinical data, melanocortin-4 receptor neuroanatomy and prior male clinical studies
The authors argued that existing preclinical and early clinical data support further evaluation of bremelanotide for male arousal and desire disorders, including possible combination with PDE5 inhibitors. No approved male indication exists and the proposed use remains investigational.
- 13Review2025
Intravenous peptides and amino acids for erectile dysfunction: a narrative review of current applications and future directions
Ila V, et al. · Expert Opinion on Pharmacotherapy · narrative review of literature through October 2024 covering PT-141, PnPP-19, L-arginine and L-citrulline
The review described PT-141 as acting through central melanocortin pathways rather than peripheral nitric oxide signalling. The authors concluded that large-scale trials are still required to establish safety, dosing and any synergistic effect with PDE5 inhibitors.
- 14Review2025
Pharmacotherapy of Hypoactive Sexual Desire Disorder in Premenopausal Women
Barakeh D, et al. · The Annals of Pharmacotherapy · narrative review of pharmacologic management of generalised acquired HSDD in premenopausal women
The review identified flibanserin and bremelanotide as the only FDA-approved treatments for generalised acquired HSDD in premenopausal women. The authors raised concerns about limited efficacy, adverse effect burden and transparency of the supporting evidence base.
- 15Review2023
Targeting the central melanocortin system for the treatment of metabolic disorders
Sweeney P, et al. · Nature Reviews Endocrinology · mechanistic review of central melanocortin (MC3R/MC4R) signalling and melanocortin-targeting therapeutics
The review summarised MC4R signalling biology and positioned bremelanotide's 2019 approval as evidence for the tolerability of melanocortin agonist peptides as a therapeutic class, alongside setmelanotide's 2020 approval for syndromic obesity.
What this evidence does not establish.
Controlled evidence is confined almost entirely to on-demand subcutaneous dosing for hypoactive sexual desire disorder in premenopausal women, where independent re-analyses dispute whether the statistically significant effects are clinically meaningful; there is no approved or adequately powered indication in men, in postmenopausal women, or for any performance, athletic or cosmetic use. Long-term safety beyond the 52-week open-label extension, cardiovascular outcomes with repeated dosing, and effects of non-approved routes or dose schedules have not been established.
Common questions about the research.
- What is PT-141?
PT-141, or bremelanotide, is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that acts as an agonist at melanocortin receptors, principally the centrally expressed MC3R and MC4R subtypes.
- How does PT-141 relate to Melanotan 2?
PT-141 is an active metabolite of melanotan II, but their receptor profiles differ. Melanotan II retains substantial MC1R activity, the subtype associated in the literature with pigmentation, whereas PT-141 is characterised as having comparatively low MC1R activity and greater relative activity at MC3R and MC4R.
- What tolerability signals appear in the published trials?
The phase 3 publications report nausea, flushing, and headache as the most frequently recorded adverse events, along with transient increases in blood pressure and reductions in heart rate following administration. These are trial observations reported for context, not safety guidance.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.