PT-141 + Oxytocin blend

PT-141 is bremelanotide, an MC3R and MC4R agonist that increases sexual desire through central melanocortin pathways in the hypothalamus rather than through any vascular mechanism - it is the reason it works in people for whom PDE5 inhibitors do nothing. Oxytocin is a nonapeptide with well-documented effects on social cognition, trust and anxiety when given intranasally, and a peripheral role in smooth muscle contraction during orgasm. The pairing rationale is that one supplies desire and the other supplies connection, which is a marketing story rather than a pharmacological one, since no study has looked at the two together. The important safety point is structural: Palatin developed bremelanotide intranasally first and abandoned that route because of blood-pressure increases, moving to subcutaneous dosing for the product that was eventually approved as Vyleesi. Buying an intranasal bremelanotide blend means using the delivery route the developer discarded on safety grounds.

Targets: MC3R and MC4R melanocortin receptors, Hypothalamic sexual desire pathways, Oxytocin receptor, Central amygdala and social cognition circuits

• · A microgram figure cannot honestly be given for this product. The milligram numbers on the label are the total contents of the bottle, not a dose, and the amount delivered per spray depends entirely on the fill volume and pump, which vendors frequently do not state. For scale, the approved subcutaneous bremelanotide dose is 1.75 mg and is capped at one dose in 24 hours and eight per month; intranasal bioavailability is lower and more variable, so people use more, which is exactly the pattern that produced the blood-pressure signal in the original trials. Work out your per-spray amount from the label before dosing, and if the label does not let you, do not use the product.

Work out your exact syringe units →

• very commonNausea— The dominant side effect of bremelanotide, affecting roughly 40 percent in the approved subcutaneous trials and strongly dose-related.
• commonTransient blood-pressure increase and heart-rate decrease— Documented in the approved subcutaneous product and the specific reason the intranasal development programme was discontinued. This is the safety issue that matters with this blend.
• commonFlushing and headache— Usually within the first hour.
• commonNasal irritation or stinging— Alternate nostrils.
• uncommonDarkening of moles, freckles and facial skin— Melanocortin-driven and cumulative with frequent use. Get any changing mole checked rather than assuming it is the peptide.
• rareEmotional flatness or over-attachment from the oxytocin arm— Inconsistently reported and hard to separate from context.

• Uncontrolled hypertension or known cardiovascular disease - bremelanotide transiently raises blood pressure and the intranasal route was abandoned over exactly this.
• Pregnancy and breastfeeding - oxytocin is uterotonic.
• History of melanoma or numerous atypical naevi.
• Concurrent use with nitrates.

• redundantpt-141 — Already in the bottle. Adding a standalone subcutaneous PT-141 dose on top stacks the blood-pressure and nausea effects.
• redundantoxytocin — The other component. Separate oxytocin is a better tool if oxytocin is what you actually want, since it can be dosed without the melanocortin load.
• redundantmelanotan-2 — Melanotan II is a non-selective melanocortin agonist and PT-141 is its metabolite. Running both is one receptor hit twice, with additive nausea and pigmentation.
• conflictNitrates — Blood-pressure effects in opposite directions with an unpredictable net result. Do not combine.
• cautionAntihypertensive medication — Bremelanotide's transient pressor effect can be unpredictable on top of blood-pressure treatment. Check your pressure after the first dose.
• cautionAlcohol — Compounds the nausea and the blood-pressure unpredictability, and it is the usual real-world context for this product.

• · Take your blood pressure before and about an hour after the first dose. This is not optional advice for this particular blend.
• · Find the per-spray delivered volume on the label and calculate what you are actually taking; the bottle contents figure is not a dose.
• · Keep a count of doses per month - the approved product caps at eight, and there is no reason to think an unapproved route is more forgiving.
• · Photograph moles at baseline if you intend to use it regularly.

Bremelanotide is FDA-approved as Vyleesi in a subcutaneous autoinjector only; an intranasal blend containing it is not an approved product. Oxytocin is a prescription drug. Nasal sprays combining the two are sold as research chemicals and are unlawful to market for human use. Prohibited in sport is not applicable to oxytocin, but tested athletes should check the current WADA list before using any melanocortin agonist.

• Kingsberg et al., RECONNECT phase 3 trials of subcutaneous bremelanotide in hypoactive sexual desire disorder (trial)
• Vyleesi (bremelanotide) prescribing information, including blood-pressure and dose-frequency limits (label)
• Palatin Technologies intranasal bremelanotide development programme and its discontinuation over blood-pressure increases (trial)
• Reviews of intranasal oxytocin effects on social cognition and their replication problems (review)

Bremelanotide is the rare libido compound that works upstream of the vasculature, and that is the whole clinical point of it. PDE5 inhibitors act on smooth muscle and blood flow, so they do nothing for someone whose problem is absent desire rather than inadequate erection. Bremelanotide is a non-selective melanocortin agonist with activity at MC1R, MC3R, MC4R and MC5R, and the desire effect is attributed principally to MC4R in the hypothalamus - the medial preoptic area and paraventricular nucleus - where melanocortin signalling engages dopaminergic and oxytocinergic pathways involved in sexual motivation. It raises desire centrally rather than enabling a response peripherally. That non-selectivity explains everything else about the compound. MC1R agonism in melanocytes drives melanogenesis, which is why repeated dosing darkens moles, freckles and facial skin - the Vyleesi label reports focal hyperpigmentation in about 1 percent of users at eight or fewer doses per month, and the rate rises with frequency. MC4R activity in autonomic centres is the most plausible explanation for the cardiovascular signature: the approved label documents peak increases of about 6 mmHg systolic and 3 mmHg diastolic with a heart rate reduction of up to 5 beats per minute, resolving usually within 12 hours. Nausea, at 40 percent versus 1.3 percent on placebo in the phase 3 programme, is central and dose-related, and it is the reason most people stop. Here is the part that matters for this specific product. Those blood-pressure numbers come from the subcutaneous route at 1.75 mg. Palatin developed bremelanotide intranasally first and abandoned that route because of blood-pressure increases, moving to subcutaneous for the product that was eventually approved. The intranasal pharmacokinetics explain why: bioavailability by that route is low and variable, effective doses were above 7 mg rather than 1.75 mg, and a variable-absorption route with a pressor effect means that on the day your absorption is good you get a dose you did not intend. Buying an intranasal bremelanotide blend means using the delivery route the developer discarded on safety grounds, at an unknown dose. Oxytocin acts at the oxytocin receptor, a Gq-coupled GPCR, with central effects on the amygdala, hypothalamus and reward circuitry that have been linked to trust, social salience and anxiety reduction, plus a peripheral role in smooth muscle contraction. The pairing rationale - one supplies desire, the other supplies connection - is a marketing story rather than a pharmacological one. It is worth adding that intranasal oxytocin has one of the worst replication records in modern neuroscience. Leng and Ludwig's review is titled Intranasal Oxytocin: Myths and Delusions, which conveys the tone of the critical literature accurately. The central question is whether a meaningful quantity reaches brain from a nasal dose at all. There is a genuine irony in that the melanocortin arm is thought to work partly through endogenous oxytocinergic pathways, so the oxytocin in the bottle may be the less useful way of engaging oxytocin signalling than the bremelanotide sitting next to it.

The first thing that goes wrong is that you do not know your dose, and with this compound that is not a bookkeeping issue. The milligram figure on the bottle is total contents. Your per-spray amount depends on fill volume and pump delivery, which vendors frequently do not state, and the ratio between the two peptides is not standardised at all - the same product name is sold as 10 mg PT-141 with 5 mg oxytocin by one supplier and 5 mg with 10 mg by another. You are self-administering a compound with a documented pressor effect at an amount you cannot calculate. The second is the route itself, and it is the reason this is the blend with the most concrete safety concern on the page. Palatin developed intranasal bremelanotide, found blood-pressure increases, and moved to subcutaneous dosing for the product that was eventually approved. Intranasal bioavailability is low and variable, effective intranasal doses in the published study were above 7 mg against an approved subcutaneous dose of 1.75 mg, and variable absorption plus a pressor effect means the day your nose absorbs well is the day you get a dose you did not intend. The third is redosing. Onset is 45 minutes to two hours - slow compared with what people expect from anything used in this context. Someone takes a dose, nothing happens in twenty minutes, they take another, and then both arrive together. That is the standard route to severe nausea and a blood-pressure spike, and it happens constantly. The fourth is nausea, which is not a minor side effect here. Forty percent in the phase 3 programme at a carefully controlled subcutaneous dose. It is strongly dose-related, it is the commonest reason people abandon bremelanotide, and it is worse with alcohol. The fifth is the frequency cap. One dose per 24 hours, no more than eight per month. People exceed it because tolerance develops, the response blunts, and escalating feels like the obvious answer. Escalating a melanocortin agonist gives you more pigmentation, more nausea and more cardiovascular effect for a diminishing return. The sixth is pigmentation, which is cumulative and slow to reverse. Moles darken, new freckles appear, facial skin can darken. The dangerous version is not the cosmetic change but the assumption that any changing mole is just the peptide. Get it looked at. The seventh is storage. Oxytocin in solution is the less stable component and degrades noticeably at room temperature. A nasal spray living in a bedside drawer is losing the oxytocin arm continuously, which is one straightforward explanation for effects becoming inconsistent over a bottle's life. Refrigerate it. The eighth is the attribution problem in its sharpest form. If the melanocortin arm makes you nauseated, you cannot keep the oxytocin without it. There is no adjustment available. The ninth applies to anyone with cardiovascular disease or uncontrolled hypertension, and it is simple: this is not a compound to experiment with. The blood-pressure effect is documented, this route amplifies its unpredictability, and the context of use frequently includes alcohol and physical exertion.

1. —First use — A microgram figure cannot honestly be given, and that is the finding rather than an omission. The milligram number on the bottle is total contents, not a dose. Your per-spray amount depends on fill volume and pump delivery, and vendors frequently state neither. Work it out from the label before dosing, and if the label does not permit that calculation, do not use the product. For scale: the approved subcutaneous dose is 1.75 mg, and intranasal doses above 7 mg were needed for a significant effect in the published intranasal study.
2. —First use, practical version — Smallest amount the pump delivers - a single spray in one nostril - on a day when nothing depends on the outcome. Measure blood pressure before and an hour after. Nausea is strongly dose-related and is the commonest reason people abandon bremelanotide, at 40 percent even in the carefully dosed approved product.
3. —Subsequent uses — Increase by one spray at a time across separate occasions, never within the same session. Onset is 45 minutes to two hours, which is slow compared with what people expect, and taking a second dose because the first has not worked yet is the single most common route to nausea and a blood-pressure spike.
4. —Ongoing frequency cap — No more than one dose in 24 hours and no more than eight doses per month. That is the approved label's cap for the subcutaneous product, it exists because of the pressor effect and cumulative melanogenesis, and there is no reason to think an unapproved route with variable absorption is more forgiving. Frequent use also blunts the response, which is the usual reason people escalate.

• MC4R (melanocortin 4 receptor), hypothalamic

  The desire mechanism. Agonism in the medial preoptic area and paraventricular nucleus engages dopaminergic and oxytocinergic pathways involved in sexual motivation. Central and upstream of the vasculature, which is why it works in people for whom PDE5 inhibitors do nothing.

• MC3R

  Also agonised. Contribution to the sexual desire effect is less clearly defined than MC4R's, and it is part of the general melanocortin activity rather than a targeted action.

• MC1R (melanocytes)

  The pigmentation mechanism. Drives melanogenesis, producing darkening of moles, freckles and facial skin with repeated use. Focal hyperpigmentation was reported in about 1 percent of users at eight or fewer doses per month in the approved product, and it increases with frequency. This is cumulative and does not reverse quickly.

• Autonomic cardiovascular centres (melanocortin-mediated)

  The transient pressor effect: peak rises of about 6 mmHg systolic and 3 mmHg diastolic with heart rate down up to 5 beats per minute, resolving usually within 12 hours. This is the documented safety signal in the approved subcutaneous product and the reason the intranasal programme was discontinued.

• Oxytocin receptor (OXTR), Gq-coupled

  Central effects on amygdala, hypothalamus and reward circuitry linked to trust, social salience and anxiety, plus peripheral smooth muscle contraction including uterine. The central effects from intranasal dosing are the contested part - how much reaches brain is genuinely unresolved.

• Endogenous oxytocinergic signalling downstream of MC4R

  Worth noting because it undercuts the product's own rationale: melanocortin agonism is thought to engage oxytocin pathways centrally as part of its mechanism. The bremelanotide may be a more reliable route to central oxytocin signalling than the intranasal oxytocin in the same bottle.

• RECONNECT Studies 301 and 302 - bremelanotide for hypoactive sexual desire disorder, two identical randomised phase 3 trials Phase 3 · n=1267 · 24 weeks · 2019

  Change from baseline in Female Sexual Function Index desire domain and in Female Sexual Distress Scale item 13. Bremelanotide 1.75 mg subcutaneously as needed improved desire (combined 0.35, P<0.001) and reduced distress (combined -0.33, P<0.001) versus placebo. Nausea, flushing and headache each occurred in at least 10 percent. These are statistically significant and clinically modest effects, and they were produced subcutaneously at a known dose - not intranasally at an unknown one.

• Simon et al, long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder (open-label extension) Phase 3 open-label extension · 2019

  Long-term safety and durability of effect beyond the 24-week double-blind period. The relevant dataset for anyone intending to use a melanocortin agonist repeatedly over months rather than occasionally.

• Diamond et al, double-blind placebo-controlled evaluation of safety, pharmacokinetics and pharmacodynamics of intranasal PT-141 in healthy males and men with mild-to-moderate erectile dysfunction Early phase, randomised placebo-controlled · 2004

  Erectile response by RigiScan plus pharmacokinetics of the intranasal route. Median tmax 0.50 hours, mean half-life 1.85 to 2.09 hours, dose-proportional Cmax and AUC, significant erectile response only above 7 mg, first erection around 30 minutes. Flushing and nausea were the commonest adverse events. This is the only published pharmacokinetic characterisation of the route this blend actually uses.

• Rosen et al, safety, pharmacokinetics and pharmacodynamics of subcutaneous PT-141 in healthy men and men with inadequate response to sildenafil Early phase · 2004

  Established the subcutaneous route in men including those who did not respond adequately to sildenafil - the finding that defined bremelanotide's clinical niche as a central rather than vascular agent.

• White et al, ambulatory blood pressure monitoring assessment of bremelanotide Cardiovascular safety study · 2017

  Formal ambulatory blood pressure characterisation of the melanocortin agonist. This is the dedicated cardiovascular safety work behind the label's blood-pressure warnings, and it is the study that makes the pressor effect a documented fact rather than a theoretical concern.

• Clayton et al, phase 1 randomised placebo-controlled double-blind study of bremelanotide coadministered with ethanol Phase 1 · 2017

  Safety and tolerability of bremelanotide with alcohol in healthy participants. Directly relevant, because alcohol is the usual real-world context for this product and the combination compounds both nausea and blood-pressure unpredictability.

0 to 30 minutes: nothing, usually. Plasma tmax intranasally is around half an hour, but the subjective effect is central and lags the plasma curve. Flushing and early nausea can start in this window and are the first sign you took a meaningful dose. 45 minutes to 2 hours: onset. This is genuinely slow for the context in which it is used, and the mismatch between that and expectation is the single most common cause of accidental overdosing. 1 to 3 hours: peak effect and peak nausea together, since both are dose-related and centrally mediated. Blood pressure, if it is going to rise, is elevated across roughly this window and the label describes resolution usually within 12 hours. 2 to 24 hours: bremelanotide's plasma half-life is about 2 hours intranasally, but reported subjective effects last far longer - up to a day or more. That is receptor-mediated central action rather than persisting drug, and it is why the frequency cap is per 24 hours despite the short half-life. Oxytocin's central effects, whatever they amount to, are usually described over one to two hours and are much shorter than the melanocortin arm's. So for most of the duration of effect, the oxytocin you paid for is no longer contributing. Over weeks of repeated use: pigmentation changes accumulate gradually and do not reverse quickly. The response tends to blunt with frequent use, which is the usual trigger for escalation. After stopping: no withdrawal. Blood-pressure effects are episodic and end with the last dose. Pigmentation fades slowly over months, and some naevus darkening may not fully reverse.

Nitrates are an absolute conflict, not a caution. Bremelanotide raises blood pressure transiently and nitrates lower it, and the net result in an individual is unpredictable. Do not combine, and that includes recreational nitrites - poppers are common in exactly the context this product is used in and this is the interaction most likely to cause an actual emergency. Antihypertensive medication needs care rather than avoidance. The pressor effect can be unpredictable on top of blood-pressure treatment, and the practical response is to measure your pressure after the first dose rather than to guess. PDE5 inhibitors are the interaction people most want to know about, and the honest answer is that the mechanisms are complementary - central desire versus peripheral vascular response - and that combining a compound which raises blood pressure with one that lowers it produces a net effect nobody has characterised at these doses by this route. The approved bremelanotide label does not endorse the combination. If you are going to do it anyway, separate them in time rather than taking both at once, and take your blood pressure. Alcohol is the realistic context and has been formally studied with bremelanotide. It compounds the nausea, which is already the dominant side effect at 40 percent, and it adds its own vasodilatory unpredictability to a compound with a pressor effect. Melanotan II is a straightforward redundancy with a specific hazard. PT-141 is the active metabolite of melanotan II, so running both is one receptor family hit twice, with additive nausea and substantially additive pigmentation. This is the stack most likely to leave you with permanent cosmetic changes. Separate oxytocin is worth considering as a replacement rather than an addition. If oxytocin is genuinely what you want, standalone intranasal oxytocin can be dosed without the melanocortin load, without the pressor effect and without the pigmentation. It also has to survive the same replication critique. SSRIs deserve a mention because they are a common cause of the problem this product is bought for. If your low desire started when your antidepressant did, the useful conversation is about the antidepressant, not about a nasal peptide.

Against subcutaneous bremelanotide: the approved product is 1.75 mg subcutaneously with essentially 100 percent bioavailability, a known dose, a known blood-pressure profile and 1,267 patients of phase 3 data behind it. The nasal blend is an unknown dose by a route the developer abandoned on safety grounds. If you want bremelanotide, the subcutaneous route is better in every respect except price and convenience, and those two are the entire reason this product exists. Against standalone PT-141: standalone removes the component with the weakest evidence and lets you dose one thing. Given that intranasal oxytocin's central effects are seriously contested, and that melanocortin agonism is thought to engage oxytocin pathways anyway, the oxytocin in this bottle may be adding cost more than effect. Against standalone oxytocin: if connection rather than desire is what you actually want, standalone intranasal oxytocin gives you that without a pressor effect, without nausea at 40 percent and without pigmentation. It also has to survive the Leng and Ludwig critique, which is a real obstacle rather than a formality. Against PDE5 inhibitors: entirely different mechanisms and not really competitors. Sildenafil and tadalafil act peripherally on vascular smooth muscle and have vastly more human data, decades of use and cheap generics. If the problem is erectile response rather than desire, a PDE5 inhibitor is the right tool and bremelanotide is not. Bremelanotide's niche is specifically people for whom desire is the deficit, or men who did not respond to sildenafil. Against melanotan II: PT-141 is melanotan II's active metabolite with far less melanogenic activity per unit of sexual effect, so PT-141 is the more targeted choice. Melanotan II's tanning is a feature for some people and a serious cosmetic and dermatological liability for others. Against addressing the cause: low desire is commonly caused by hypogonadism, hyperprolactinaemia, thyroid disease, depression, SSRIs, alcohol, sleep debt and relationship context. Every one of those is more treatable than it is fashionable. A nasal melanocortin agonist is a reasonable thing to try after those are excluded and a poor way to avoid excluding them.

$0–$60/month. This is used episodically rather than daily, so the monthly figure depends entirely on frequency. A 15 mg pre-mixed nasal bottle has generally sold in the forty to ninety dollar range and, used within the eight-doses-per-month cap that the approved product specifies, will last well over a month - often several. Someone using it twice a month spends almost nothing; someone using it weekly and exceeding the cap spends more and gets a blunted response. For comparison, the approved subcutaneous product is dramatically more expensive per dose, which is the honest reason this grey-market version exists. Observed market ranges, not verified against current vendor pricing this session.

• ?The ratio in this blend is genuinely not standardised. Vendors sell PT-141 to oxytocin at both 10:5 and 5:10, so the product name conveys no information about contents.
• ?No study of bremelanotide and oxytocin together exists at any dose by any route.
• ?Intranasal bremelanotide bioavailability was not quantified in the study I could verify. The inference that it is a fraction of subcutaneous comes from comparing the above-7 mg effective intranasal dose with the 1.75 mg approved subcutaneous dose, which is reasoning rather than measurement.
• ?The pharmacokinetic values recorded in the structured fields - volume of distribution 25 L, protein binding 21 percent, clearance 6.5 L/h - are from the approved subcutaneous product and do not necessarily describe the intranasal route. The tmax of 0.5 hours is the intranasal figure from Diamond et al.
• ?No pharmacokinetic data exists for intranasal oxytocin's central exposure, and whether meaningful quantities reach brain at all is actively contested in the literature.
• ?The specific reason Palatin discontinued intranasal bremelanotide is described in the Core entry as blood-pressure increases. I did not independently resolve a primary source documenting that discontinuation decision in this session, so treat the causal account as widely reported rather than verified here. The blood-pressure effect itself is verified from the approved label and from the ambulatory monitoring study.
• ?No verified receptor binding affinity figures were resolved for bremelanotide at MC1R, MC3R or MC4R, so those fields are left empty.
• ?Molecular weights for both components are omitted deliberately - neither was verified in this session.
• ?The oxytocin hyponatraemia risk is extrapolated from obstetric use at much higher doses with large fluid volumes. Whether it is relevant at intranasal blend doses is unknown, and I found no case reports at these amounts.
• ?Participant numbers and durations for the Diamond, Rosen, White, Clayton and Simon studies were not resolved, so those fields are null despite each trial being verified as existing.
• ?The frequency cap of eight doses per month is taken directly from the approved subcutaneous label. Whether it is the right cap for an unapproved route at an unknown dose is unknown - it is the most conservative available anchor, not a validated limit for this product.
• ?How quickly melanocortin-driven pigmentation reverses after stopping is not well characterised, and the statement that some naevus darkening may not fully reverse is clinical impression rather than documented outcome.
• ?Cost ranges are general market observation and were not verified against current vendor pricing this session.
• ?Component structures in the modifications array are established chemistry but were not independently resolved this session, hence verified false.

• Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA, Obstetrics and Gynecology, 2019 · PMID 31599840

  The RECONNECT phase 3 programme: 1,267 women, 24 weeks, 1.75 mg subcutaneously as needed. Every efficacy claim for the PT-141 component traces here. Read the effect sizes - they are statistically robust and clinically modest, and they were produced by a route this blend does not use.

• Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH, Obstetrics and Gynecology, 2019 · PMID 31599847

  The open-label extension. The right paper for anyone planning repeated use over months rather than occasional use, and the source of the cumulative hyperpigmentation picture.

• 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, Earle DC, Rosen RC, Willett MS, Molinoff PB, International Journal of Impotence Research, 2004 · PMID 14963471

  The only published pharmacokinetic study of intranasal bremelanotide - the route this product uses. Median tmax 0.50 hours, half-life 1.85 to 2.09 hours, effective doses above 7 mg. Read it against the 1.75 mg subcutaneous approved dose and the size of the gap will tell you why nasal dosing is hard to control.

• Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB, International Journal of Impotence Research, 2004 · PMID 14999221

  The subcutaneous companion study and the origin of bremelanotide's central-mechanism claim - it worked in men who did not respond to sildenafil, which is the reason anyone cares about melanocortin agonists for sexual function.

• Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide White WB, Myers MG, Jordan R, Lucas J, Journal of Hypertension, 2017 · PMID 27977473

  The dedicated cardiovascular safety study. This is why the blood-pressure caution on this blend is a documented pharmacological property rather than defensive hedging, and why measuring your own pressure around the first dose is the specific advice.

• Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants Clayton AH, Lucas J, DeRogatis LR, Jordan R, Clinical Therapeutics, 2017 · PMID 28189361

  Bremelanotide with alcohol, formally studied. Worth reading because alcohol is the usual real-world context for this product and this is the only controlled look at that combination.

• VYLEESI (bremelanotide) injection - full prescribing information DailyMed / FDA prescribing information

  The source of every hard pharmacokinetic and safety number in this record: tmax about 1.0 hour, absolute subcutaneous bioavailability about 100 percent, 21 percent protein binding, volume of distribution 25.0 L, terminal half-life about 2.7 hours, clearance 6.5 L/h, 64.8 percent urinary and 22.8 percent faecal excretion, peak blood pressure rise of 6/3 mmHg with heart rate down up to 5 bpm, nausea 40 percent versus 1.3 percent on placebo, flushing 20.3 percent, injection site reactions 13.2 percent, focal hyperpigmentation about 1 percent at eight or fewer doses per month, and the one-dose-per-24-hours and eight-doses-per-month caps. If you use this blend, read the label of the approved version of half of it.

• Intranasal Oxytocin: Myths and Delusions Leng G, Ludwig M, Biological Psychiatry, 2016 · PMID 26049207

  The essential corrective on the oxytocin half of this bottle. Argues that the quantities reaching brain after intranasal dosing are far too small to explain the reported behavioural effects. If you are paying extra for the oxytocin component, read this before you decide it is worth it.

• Oxytocin - a social peptide? Deconstructing the evidence Leng G, Leng RI, Ludwig M, Philosophical Transactions of the Royal Society B, 2022 · PMID 35858110

  The more recent and more thorough deconstruction of the intranasal oxytocin literature, including its publication bias and replication problems.

• Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis Keech B, Crowe S, Hocking DR, Psychoneuroendocrinology, 2018 · PMID 29032324

  A quantitative meta-analysis of intranasal oxytocin on social cognition, giving the effect sizes rather than the narrative. Useful for calibrating how much the oxytocin arm of this blend is realistically contributing.

• Intranasal oxytocin effects on social cognition: a critique Evans SL, Dal Monte O, Noble P, Averbeck BB, Brain Research, 2014 · PMID 24239931

  Methodological critique of the intranasal oxytocin literature, including dose, timing and blinding problems that affect most of the studies vendors cite.