Compound reference
PT-141
Also known as Bremelanotide, Vyleesi
PT-141 (bremelanotide) is the melanotan-II-derived melanocortin agonist that became Vyleesi — FDA-approved in 2019 for premenopausal women with hypoactive sexual desire disorder. Unlike its parent, it is a genuinely trialed, approved drug — but with modest effect sizes and a narrow label, and the gray-market "PT-141" used by men is outside both.
- CAS
- 189691-06-3
- Sequence
- Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH — the C-terminal-acid analogue/metabolite of melanotan II
FDA-approved prescription medicine for acquired generalized hypoactive sexual desire disorder in certain premenopausal women.
Mode of action
PT-141 — bremelanotide — is a cyclic melanocortin-receptor agonist derived from Melanotan II (it is the C-terminal-acid analogue of that peptide). Its therapeutic action is central, not vascular: it activates melanocortin receptors — the relevant one being MC4R, densely expressed in the medial preoptic area of the hypothalamus — where receptor agonism is thought to increase dopamine release and thereby raise sexual desire. That places it in the appetitive/desire arm of the sexual-response pathway, mechanistically distinct both from PDE5 inhibitors such as sildenafil (which act peripherally on vascular tissue and require sexual stimulation) and from flibanserin (a serotonergic agent). Preclinical work localising the effect to dopamine terminals in the medial preoptic area underpins this model.
Main intended effect
To increase sexual desire — specifically, to treat hypoactive sexual desire disorder (HSDD).
Areas of interest
The approved use is acquired, generalised HSDD in premenopausal women, marketed as Vyleesi. Historically, the same central-erectogenic mechanism was pursued for erectile dysfunction with an intranasal formulation, but that development was halted over blood-pressure increases and the program pivoted to the subcutaneous HSDD product. Off-label and on the gray market, PT-141 is sold broadly as a libido enhancer for men and women.
Evidence for intended effects
Unlike most research peptides, PT-141 is a properly trialed and approved drug — though its effect sizes are modest. The pivotal RECONNECT program (Kingsberg and colleagues, 2019) comprised two identical phase 3 randomised, double-blind, placebo-controlled trials in 1,267 premenopausal women with HSDD; as-needed subcutaneous bremelanotide 1.75 mg significantly improved the Female Sexual Function Index desire domain (integrated +0.35, p<0.001) and reduced sexual-distress scores (−0.33, p<0.001) versus placebo. A 52-week open-label extension (Simon, 2019) reported no new safety signals, albeit with high (>60%) dropout. The central mechanism is supported by preclinical and neurobiology reviews. The honest caveats: the benefits are statistically real but small, the trial populations were predominantly white and US-based, and there is no comparable approved evidence for use in men or for erectile dysfunction.
| Strand | What exists | Tier |
|---|---|---|
| HSDD in premenopausal women | Two phase 3 RCTs (RECONNECT); FDA approval (Vyleesi) | Established / approved (modest effect) |
| Long-term tolerability | 52-week open-label extension | Supportive (high dropout) |
| Mechanism | Preclinical + neurobiology reviews | Well characterized |
| Men / erectile dysfunction | No approved evidence; ED program halted | Unproven |
Studied amounts (literature dosing context)
The approved product is bremelanotide 1.75 mg in 0.3 mL, given subcutaneously as needed via a single-dose autoinjector, no more than once per 24 hours and no more than eight doses per month. These are label figures for the approved indication; this page does not provide dosing guidance.
Safety and regulatory status
In its approved use, bremelanotide's most common adverse effects are nausea (about 40%), flushing (~20%), injection-site reactions (~13%) and headache (~11%); it causes transient, usually small increases in blood pressure (around 6/3 mmHg) with a modest fall in heart rate that typically resolve within 12 hours, and it can cause focal hyperpigmentation with repeated dosing. It is not indicated for postmenopausal women or for men. Vyleesi is an FDA-approved prescription drug (2019) — but the material sold online as "PT-141" is unregulated, of unverified identity and purity (PT-141 has been named in regulatory seizures), and is frequently used outside the narrow population and indication for which it was approved and is medically monitored.
Sources
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials
Pivotal RECONNECT program (Kingsberg, Clayton, Simon, et al.): two identical phase 3 randomized double-blind placebo-controlled trials (Studies 301 and 302) enrolling 1,267 premenopausal women with HSDD, randomized 1:1 to bremelanotide 1.75 mg subcutaneously as-needed or placebo for 24 weeks. On the coprimary Female Sexual Function Index-desire domain, bremelanotide improved scores by an integrated 0.35 (P<0.001), and on the Female Sexual Distress Scale-DAO item 13 it reduced distress by an integrated -0.33 (P<0.001), with consistent direction across both studies. The most frequent treatment-emergent adverse events were nausea, flushing, and headache (>=10% in both studies), mostly mild to moderate. Generalizability is limited by a predominantly white (85.6%) and US-recruited (96.6%) population.
Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder
52-week open-label extension (Simon, Kingsberg, et al.) of the RECONNECT phase 3 trials evaluating long-term tolerability of bremelanotide 1.75 mg subcutaneous as-needed in premenopausal women with HSDD; of 856 women completing the initial 24-week phase, 684 enrolled in the extension and 272 completed it. The most common treatment-related adverse events were nausea (40.4%), flushing (20.6%), and headache (12.0%), with nausea the only severe event affecting more than one participant in both studies, and no new safety signals identified. Women previously on bremelanotide maintained improvements in sexual desire versus prior placebo. The analysis was descriptive rather than inferential, and dropout exceeded 60%, which may bias the tolerability picture toward those who tolerated treatment.
VYLEESI (bremelanotide injection), for subcutaneous use — Prescribing Information
FDA prescribing information (DailyMed) for VYLEESI (bremelanotide injection) by Palatin Technologies, indicated for premenopausal women with acquired, generalized HSDD characterized by low sexual desire causing marked distress or interpersonal difficulty, with initial US approval in 2019. The dose is 1.75 mg in 0.3 mL subcutaneously via single-dose prefilled autoinjector, no more than once per 24 hours and not more than 8 doses per month. Labeling describes transient post-dose increases in blood pressure (maximal ~6 mmHg systolic, 3 mmHg diastolic) and decreased heart rate (up to 5 bpm) usually resolving within 12 hours. Most common adverse reactions are nausea (40%), flushing (20.3%), injection-site reactions (13.2%), and headache (11.3%); it is not indicated in postmenopausal women or men.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c9607a2-5b57-4a59-b159-cf196deebdd9
Bremelanotide: an overview of preclinical CNS effects on female sexual function
Preclinical overview (Pfaus, Giuliano, Gelez) of bremelanotide, an alpha-MSH analogue and melanocortin receptor agonist, tested in ovariectomized hormone-primed female rats in paradigms where animals controlled the timing of sexual contact. Both peripheral subcutaneous administration and direct infusion into the lateral ventricles or medial preoptic area (mPOA) dramatically and selectively increased solicitation behaviors without altering pacing or lordosis, implicating activation of dopamine terminals in the mPOA as the appetitive-desire mechanism. The work localizes the central site of action relevant to female sexual desire rather than peripheral arousal. Findings are in rodent models and the authors note the need for translation to human clinical contexts.
The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women
Narrative review (Pfaus, Sadiq, Spana, Clayton) of the melanocortin system underlying bremelanotide's action in HSDD. It describes melanocortins as endogenous neuropeptides in the excitatory pathway of the female sexual response, with the therapeutically relevant MC4R predominantly expressed in the medial preoptic area of the hypothalamus, where receptor agonism is proposed to increase dopamine release and thereby sexual desire. The review contrasts bremelanotide's melanocortin-agonist mechanism with flibanserin's serotonergic mixed agonist/antagonist action, framing the two approved HSDD agents as mechanistically distinct. As a mechanism-focused review it does not present new efficacy or safety data.
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization
Hadley and Dorr review the development of melanocortin peptide therapeutics, tracing milestones from α-MSH biology through clinical candidates and commercialization. Melanotan I, a linear superpotent α-MSH analog, was advanced for skin tanning and potential reduction of skin-cancer risk, while Melanotan II, a cyclic truncated analog, was originally tested for tanning but — owing to its erectogenic side effect — was redirected toward male erectile dysfunction; the MT-II-derived analog PT-141 (bremelanotide) was then developed and commercialized for sexual dysfunction in both sexes. Written by investigators central to the field, this is a historical and commercialization review rather than primary data.
Use of melanotan I and II in the general population
Evans-Brown and colleagues describe the spread of the synthetic melanocortin analogues Melanotan I and Melanotan II into general, non-clinical use, driven by their skin-tanning effects and — for MT-II — induction of penile erections and increased sexual desire. The authors note the drugs are unlicensed yet easily obtained online and sold or administered in tanning salons, beauty parlours, and hairdressers, and they summarize development status: Melanotan I (afamelanotide) was in phase III trials as a photoprotective agent, while Melanotan II had earlier been developed for sexual dysfunction, yielding the analog/metabolite bremelanotide (PT-141). This is a short BMJ awareness piece on unregulated population use; both peptides were unlicensed for cosmetic use.
Melanotan
Mahiques-Santos's opinion article frames melanotan for dermatologists. It explains that melanotan is a synthetic α-MSH analog and distinguishes Melanotan I ([Nle4-D-Phe7]-α-MSH, a 13-amino-acid linear peptide, more melanin-selective, developed as the photoprotectant afamelanotide/SCENESSE) from Melanotan II (a shorter lactam-ring cyclic analog, less receptor-selective, which also suppresses appetite and increases libido and seeded the PT-141 program). The author reviews potential medical uses (photoprotection in erythropoietic protoporphyria and other photodermatoses; central erectogenic activity), then details black-market "Barbie drug" use and its harms — eruptive melanocytic naevi, changes in pre-existing nevi, a reported melanoma (without established causation), hypertension, and injection/needle-sharing infection risk — and advises clinicians to suspect, investigate, and report illicit use. An opinion/review article; unlicensed cosmetic use is discouraged pending completion of clinical trials.