PT-141 Guide: Evidence & Sourcing

PT-141 at a glance

What it is

Bremelanotide, a synthetic cyclic seven-residue melanocortin peptide, developed from the alpha-MSH analogue melanotan II. Known in research settings as PT-141; the approved product is Vyleesi.

Approval status

FDA-approved in 2019 as Vyleesi (bremelanotide injection) for acquired, generalised hypoactive sexual desire disorder in premenopausal women. Supplied as a 1.75 mg / 0.3 mL single-dose autoinjector; the current label is held by Cosette Pharmaceuticals and was last updated in November 2025.

Mechanism, per the label

A melanocortin receptor agonist that nonselectively activates several receptor subtypes, binding principally at MC1R and MC4R. The label states plainly that the mechanism by which it improves the approved condition is unknown.

Approved dose

1.75 mg subcutaneously into the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity. No more than one dose in 24 hours, and no more than eight doses per month.

Half-life

Approximately 2.7 hours, with a reported range of 1.9 to 4.0 hours. Tmax is about 1 hour. These are measured label values, not estimates.

Bioavailability

About 100% by the subcutaneous route - unusually high, and one of the few peptides where the label states it outright. Plasma protein binding 21%, volume of distribution 25.0 +/- 5.8 L.

Most common adverse reaction

Nausea, in 40.0% of patients on drug against 1.3% on placebo - a 30-fold difference and by a wide margin the dominant tolerability issue.

The dosing-frequency finding

Focal hyperpigmentation occurred in 1% of patients taking up to eight doses per month, but in 38% of patients dosed daily for eight days. Frequency, not dose size, is what drove it - which matters because research-market use often ignores the monthly cap.

Contraindications, per the label

Uncontrolled hypertension or known cardiovascular disease. Bremelanotide transiently raises blood pressure in everyone who takes it.

Research-market status

PT-141 sold as a lyophilised research vial is not the approved product, is not approved for use in any person in that form, and is supplied for research and educational use only.

Educational reference. This page does not publish dose ranges or reconstitution arithmetic.

What it is / mechanism

Bremelanotide is a cyclic seven-residue peptide that acts on the melanocortin receptor family, and its origin explains most of its behaviour. It descends from melanotan II, a synthetic analogue of alpha-melanocyte-stimulating hormone that was developed for tanning; bremelanotide is a metabolite of that compound, refined into its own drug. Understanding that lineage explains both what it does and its most distinctive side effect, because the melanocortin family is where pigmentation and central arousal signalling happen to sit next to each other. The label describes it as a melanocortin receptor agonist that nonselectively activates several receptor subtypes, with binding principally at MC1R and MC4R. That nonselectivity is the whole story. MC4R is expressed in the central nervous system and is the receptor thought to be relevant to the approved indication; MC1R sits on melanocytes and governs melanin production. A drug that agonises both will act centrally and, given enough exposure, will also darken skin - not as an unrelated toxicity but as an on-target effect at the wrong receptor. What the label conspicuously does not do is claim to know how the drug works for its indication. It states that the mechanism by which bremelanotide improves hypoactive sexual desire disorder is unknown. That is a striking sentence to find in an approved label, and it is worth quoting accurately, because research-market pages routinely present a confident central-pathway mechanism that the regulator's own document declines to assert. What is established is the receptor pharmacology; what is inferred is the route from receptor to effect. The route of administration matters mechanistically too. Bremelanotide is given subcutaneously and its subcutaneous bioavailability is approximately 100% - the label's own figure. Essentially all of an injected dose reaches circulation, which is unusual and makes the relationship between injected amount and systemic exposure unusually direct. There is no first-pass loss to absorb variability, so an error in measuring a dose translates proportionally into an error in exposure. Metabolism is by multiple hydrolyses of the amide bonds in the cyclic peptide, and elimination is split between routes: in the mass-balance study, 64.8% of total radioactivity was recovered in urine and 22.8% in faeces. Distribution is modest, with a volume of distribution of 25.0 +/- 5.8 L and plasma protein binding of 21%, so the drug is not extensively tissue-sequestered or heavily bound. Combined with a half-life of roughly 2.7 hours, this is a compound that arrives quickly, does not linger, and does not accumulate on the approved intermittent schedule - which is precisely why the schedule is intermittent.

Researched effects

The approved effect claim is narrow and specific: Vyleesi is indicated for acquired, generalised hypoactive sexual desire disorder in premenopausal women, defined in the label as low sexual desire causing marked distress or interpersonal difficulty and not accounted for by a co-existing medical or psychiatric condition, relationship problems, or the effects of a medication or drug substance. Each of those exclusions is part of the indication, not fine print - the approved population is defined as much by what has been ruled out as by what is present. Several things about the approved use are routinely lost in translation to the research market. The drug is used episodically, on demand, at least 45 minutes before anticipated activity - it is not a daily or continuous therapy. It is approved only in premenopausal women; the label's indication does not extend to men or to postmenopausal women, whatever the research-market usage pattern suggests. And the approval is for a desire disorder, which is a different clinical target from erectile function, though the two are habitually conflated in commercial copy about PT-141. The tolerability profile is a large part of the honest picture, because it is unusually prominent for an on-demand product. In the controlled trials, nausea occurred in 40.0% of patients receiving bremelanotide against 1.3% on placebo. Flushing occurred in 20.3% against 0.3%. Headache occurred in 11.3% against 1.9%, injection-site reactions in 13.2% against 8.4%, and vomiting in 4.8% against 0.2%. Two of those - nausea and flushing - separate from placebo by more than an order of magnitude, so they are attributable effects rather than background noise. The label notes that nausea improves for most patients with the second dose, which is a genuinely useful piece of information and one of the few reassuring details in the table. The blood-pressure effect is best understood as a predictable pharmacological action rather than an adverse event that happens to some people. Bremelanotide produces transient increases in blood pressure after every dose, with maximal mean rises of about 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after dosing and generally resolving within 12 hours. Those mean increases are modest, and in a healthy person they are unremarkable; the label nonetheless contraindicates the drug in uncontrolled hypertension or known cardiovascular disease, because a reliable pressor effect in someone whose cardiovascular reserve is already compromised is a different proposition from the same effect in someone whose is not. What is reported in research-community settings - use by men, use for erectile response, use at frequencies far above the approved cap - has no controlled data behind it in the form the market uses. It is not supported by the approved label, which covers a different population and a different endpoint. Nothing on this page is a claim that PT-141 treats, prevents or improves any condition, and nothing here is medical advice.

Research timeline

Dated milestones taken from the primary records: the molecule's discovery, its first registered human study, the trials that shaped the evidence and the regulatory decisions. Each entry links to the record it comes from.

1. Feb 2004Palatin Technologies publishes the first human studies of PT-141, given as a nasal spray to healthy men and men with erectile dysfunction: a half-life of about two hours, an erectile response greater than placebo, and flushing and nausea as the most common adverse events. PMID 14963471
2. Jul 2006The first study in women (18 premenopausal women with sexual arousal disorder, one dose of bremelanotide and one of placebo each) reports more women with moderate or high desire after bremelanotide, but no measurable change in genital blood flow. PMID 16839319
3. Apr 2008A single-author trial of bremelanotide in women with arousal disorder appears in The Journal of Sexual Medicine. The journal later retracted it after the author did not supply his original data, so its results cannot be relied on. PMID 18179455 (retracted)
4. Jun 2016A 12-week dose-finding trial of as-needed bremelanotide in premenopausal women (327 in the efficacy analysis) reports 0.7 more satisfying sexual events a month at the two higher doses against 0.2 with placebo; nausea, flushing and headache were the adverse events reported. PMID 27181790
5. Apr 2017A 24-hour blood-pressure monitoring trial in 397 premenopausal women finds small, short-lived rises in systolic pressure of about 3 mmHg against placebo after bremelanotide, with a fall in heart rate. PMID 27977473
6. Jun 21, 2019FDA approves Vyleesi (bremelanotide) as a new molecular entity for premenopausal women with acquired, generalised hypoactive sexual desire disorder. The label excludes postmenopausal women and men. FDA · Drugs@FDA 210557
7. Nov 2019The two phase 3 RECONNECT trials (1,267 premenopausal women, 24 weeks) are published: desire scores rose and desire-related distress fell more than with placebo; nausea, flushing and headache each affected 10% or more of women on bremelanotide. PMID 31599840

Records checked Oct 3, 2026

Claims at a glance

The claims most often made about this compound, each with the strongest kind of evidence we found for it. The grade says what was studied, not whether the claim is true; the line beside it says what that study showed.

• Increases sexual desire in womenHuman, randomised trial. Two phase 3 trials, 1,267 premenopausal women with low-desire disorder: desire and distress improved more than on placebo, by a modest margin, over 24 weeks. PMID 31599840
• Improves erections in menHuman, randomised trial. In 342 men who had not responded to sildenafil, a positive result in 33.5% against 8.5% on placebo (2008); the men's programme never led to an approval. PMID 18206919
• Works after menopause tooNo study found. The phase 3 trials enrolled premenopausal women only, and FDA's label states it is not indicated after menopause or in men. FDA label · Vyleesi (NDA 210557)
• Tans or darkens the skinHuman, randomised trial. Patchy darkening of the face, gums or breasts in 1% in the phase 3 trials, none on placebo, and far more often with daily use; FDA lists it as a warning, and it did not always fade. FDA label · Vyleesi (NDA 210557)
• Is well toleratedHuman, randomised trial. In the phase 3 trials 18% stopped because of side effects against 2% on placebo, nausea alone accounting for 8%. FDA label · Vyleesi (NDA 210557)

The reasoning behind each grade, study by study, is in this guide's Benefit & Outcome Review.

Grades checked Oct 5, 2026

Half-life & pharmacokinetics

PT-141 has a properly measured human half-life, which distinguishes it from most compounds in this market: approximately 2.7 hours, with a reported range of 1.9 to 4.0 hours. Tmax is about 1 hour, with a range of 0.5 to 1.0 hours. Both figures come from the approved label rather than from inference or animal scaling. Those two numbers explain the approved dosing instruction better than any narrative could. Being told to inject at least 45 minutes before anticipated activity is simply an instruction to let the compound reach peak concentration, which happens at around an hour. A 2.7-hour half-life then means the great majority of a dose has cleared within a working day - after four half-lives, roughly eleven hours, only a few per cent remains. That short exposure window is why the approved product is an on-demand treatment rather than a daily one, and why no accumulation is expected on the approved schedule. It also frames why dosing frequency, not dose size, is the axis the label warns about. Because clearance is quick, taking the compound daily does not produce dramatic accumulation of drug in plasma - yet daily dosing for eight days still produced focal hyperpigmentation in 38% of patients against 1% at the approved monthly cap. The pigmentation effect tracks repeated receptor stimulation over time rather than a high peak concentration, which is exactly the pattern one would expect from an MC1R-mediated effect on melanocytes. A short half-life is not, on its own, protection against the consequences of frequent use.

Storage & handling

• Approved product, for reference: store at or below 25 degrees Celsius, do not freeze, protect from light - the label's own instruction for the ready-to-use autoinjector.
• Research-market lyophilised powder, unopened: store cold; the dry form is the stable one and tolerates shipping without refrigeration for short periods.
• Reconstituted with bacteriostatic water: refrigerate at roughly 2-8 degrees Celsius and protect from light. Commonly reported usable windows of several weeks are handling conventions, not stability data measured for this peptide in this format.
• Avoid repeated freeze-thaw cycles; direct the diluent down the vial wall rather than shaking, and wipe the stopper with alcohol before each entry.

Evidence File

The PT-141 Evidence File: An Approved Drug, 1,247 Women, and a Label That Excludes Almost Everyone Buying It

PT-141 is the rare research-market compound that is also a licensed medicine. It is bremelanotide, sold as VYLEESI under NDA210557, and that changes what an evidence file can do: instead of reconstructing a record from scattered papers, it can read the regulator's own conclusions, the trial data those conclusions rest on, and the restrictions the regulator imposed. What emerges is a genuine efficacy signal in a tightly defined population and a set of limits the research market has quietly detached from the molecule. The approved indication is premenopausal women. The label says in terms that it is not indicated in men and not indicated to enhance sexual performance. It carries a monthly dose ceiling, a cardiovascular contraindication, and a pigmentation warning that the label itself says did not always resolve. Every figure below comes from the label or the registry, not from secondary sources.

• FDA approved — NDA210557, UNII PV2WI7495P, subcutaneous
• 1,247 premenopausal women across two identical Phase 3 trials
• 18% discontinued for adverse events vs 2% on placebo
• Label limits: not indicated in men; no more than 8 doses per month
• 1 retracted paper in the published record

Sourcing File

The PT-141 Sourcing File: A Cyclic Heptapeptide With a D-Amino Acid, and an FDA Label That Does the Salt Arithmetic For You

Bremelanotide is structurally the most demanding compound in this tranche to make correctly and the easiest to verify against an authoritative reference, because an approved product exists and its label states the composition exactly. It is a cyclic heptapeptide containing a D-amino acid and an acetylated N-terminus — three synthesis features that each introduce a distinct failure mode, and two of which are invisible to the analytical methods most certificates rely on. The label also does something unusually useful: it states both the free-base and the acetate-salt mass of the same dose, which turns the salt-content question from an abstraction into a worked example with an official answer.

• Cyclic heptapeptide: Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH)
• 1.75 mg free base = 1.89 mg acetate salt — 92.6% net peptide, from the label
• Contains D-Phe — invisible to standard amino acid analysis
• MW 1025.2 free base; formula C50H68N14O10 · xCH3COOH, 1 ≤ x ≤ 2

Benefit & Outcome Review

The PT-141 Benefit and Outcome Review: What Was Proven, in Whom, and How Far It Transfers

Bremelanotide is one of very few compounds in this library where the answer to what was proven is genuinely something. Two large randomised placebo-controlled trials in 1,247 women produced a result a regulator accepted, and this review does not pretend otherwise. The harder and more useful question is transfer: the proven population is premenopausal women with a specific diagnosed condition, and the buying population is largely not that. Each claim below is graded on what was measured, in whom, at what effect size, and whether the evidence reaches the person likely to be reading. Where the honest answer is that a benefit is real but was never tested in you, this review says exactly that rather than splitting the difference.

• 5 marketed claims assessed against the label and registry
• 1 proven in a randomised trial — in premenopausal women only
• 18% stopped for adverse events; 8% for nausea alone
• 0 male indication trials registered in roughly two decades

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