Shop by category
Growth Hormone Axis ResearchRegeneration ResearchPeptide BioregulatorsCognitive & Neuropeptide ResearchMetabolic & Cellular ResearchMelanocortin & Endocrine ResearchDermal Peptide ResearchImmune & Thymic ResearchResearch & info
Research HubReference LibraryEducationCompareBlogCOAsContactAboutFAQCalculatorGlossary
Reviewed by Dr. Martina Rossi, PhD
Scientific Contributor and Reviewer · Reviewed
PT-141 is bremelanotide, a synthetic cyclic heptapeptide lactam and an analogue of alpha-melanocyte-stimulating hormone. PubChem resolves CAS 189691-06-3 to CID 9941379, formula C50H68N14O10, molecular weight 1025.2 [15]. That record is the free base [15].
The approved bremelanotide product does not contain the free base. Drugs@FDA lists the active ingredient of VYLEESI as bremelanotide acetate [14]. The acetate is a separate PubChem record, CID 91971505, CAS 1607799-13-2, formula C52H72N14O12, molecular weight 1085.2 [15]. The catalogue lists the free-base CAS, 189691-06-3, which is not the CAS of the substance inside the approved autoinjector, and it does not state whether the research powder is the free base or a salt.
PubChem lists melanotan II separately, as CID 92432, CAS 121062-08-6, formula C50H69N15O9 [15]. Its systematic name ends in carboxamide where bremelanotide's ends in carboxylic acid, so bremelanotide is the deamidated form [15]. Their regulatory positions run in opposite directions. A field-qualified query of FDA's Drugs@FDA data returns no match for melanotan II as a substance name, so it holds no US approval [23]. Melanotan II appears on FDA's page of bulk drug substances that may present significant safety risks in compounding, among substances previously in category 2 whose nominations were withdrawn [19]. FDA's rationale there cites published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism [19]. Neither "bremelanotide" nor "PT-141" appears anywhere on that list [19]. Neither compound's status transfers to the other.
Bremelanotide holds a current US approval. Drugs@FDA records NDA 210557, sponsor Cosette, with the original application approved on 21 June 2019 and a supplement approved on 23 October 2020 [14]. The product is VYLEESI, a subcutaneous autoinjector carrying prescription marketing status [14]. Its FDA label has an effective date of 13 November 2025, so this is a current record rather than a legacy one [2].
The indication is narrow, and the label states it exactly. VYLEESI is indicated for premenopausal women with acquired, generalized hypoactive sexual desire disorder, or HSDD [2]. The label defines that as low sexual desire causing marked distress or interpersonal difficulty [2]. The same sentence excludes desire problems due to a co-existing medical or psychiatric condition, problems with the relationship, or the effects of a medication or drug substance [2]. Those three exclusions are part of the indication, not commentary on it.
The label then limits its own use, in its own words: "VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men. VYLEESI is not indicated to enhance sexual performance." [2]
The approved product is a metered, single-dose prefilled autoinjector of bremelanotide acetate, dispensed on prescription after a clinical diagnosis [2][14]. Its label does not recommend more than eight doses in a month [2]. It is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease [2]. The label also directs that the medicine be discontinued after 8 weeks if the patient reports no improvement in her symptoms [2]. None of those conditions attach to a vial of research powder.
In the European Union and Canada the position differs. The European Medicines Agency publishes no assessment report for Vyleesi, and Health Canada's drug product database returns no record for the brand or the ingredient [21]. That is an absence of central EU authorization and of Canadian authorization; the national registers of individual EU member states were not checked. It is not a refusal and not a withdrawal, and no record of either was found [21].
(human, regulatory) The label describes bremelanotide as a melanocortin receptor agonist that nonselectively activates several subtypes, in the potency order MC1R, MC4R, MC3R, MC5R, MC2R [2]. It states that binding at MC1R and MC4R is the most relevant at therapeutic dose levels [2]. It also states plainly that "The mechanism by which VYLEESI improves HSDD in women is unknown." [2] The regulator asserts no established causal pathway for the effect in HSDD.
The pigmentation part of the mechanism is understood. The label records that MC1R is expressed on melanocytes, and that binding there leads to melanin expression and increased pigmentation [2].
(human) RECONNECT was two identical randomized, double-blind, placebo-controlled Phase 3 trials, NCT02333071 and NCT02338960 [1]. Of 1,267 women randomized, 1,247 formed the safety population and 1,202 the modified intention-to-treat population [1]. Participants were 85.6% white and 96.6% from US sites, with a mean age of 39 [1]. The RECONNECT publication labels the pair study 301 and study 302, and the FDA label for VYLEESI calls the same two trials study 1 and study 2 [1][2].
(human) Both RECONNECT co-primary endpoints reached statistical significance. The placebo-subtracted increase in the FSFI desire domain was 0.30 in study 301 and 0.42 in study 302, integrated 0.35, all P<.001 [1]. The placebo-subtracted reduction in FSDS-DAO item 13 was -0.37 and -0.29, integrated -0.33 [1].
Those figures only mean something on their scales. The FSFI desire domain runs from 1.2 to 6.0, and the trials' own responder threshold was an increase of at least 1.2 points [2]. FSDS-DAO item 13 runs from 0 to 4, and its responder threshold was a decrease of at least 1 point [2]. Those thresholds define a meaningful change for an individual patient, not a minimum difference between group averages, so the placebo-subtracted means above cannot be judged against them directly [2][7].
(human) The endpoint closest to lived experience did not move. The label states there was no significant difference between groups in the change in the number of satisfying sexual events, a secondary endpoint [2]. Mean change was 0.0 against -0.1 in study 1, and 0.0 against 0.0 in study 2, with p values of 0.76 and 0.70 [2]. Median change was zero in all four arms [2].
(human) Dropout was heavily asymmetric. More patients on drug than on placebo failed to complete the 24-week double-blind period, at 40% against 13% in study 1 and 39% against 25% in study 2 [2]. The label states that an exploratory analysis of patients who completed the treatment period was performed because of that imbalance [2]. An efficacy estimate is fragile when roughly four in ten assigned participants never reach the endpoint.
(human) The size of the desire and distress effects is hard to judge without a comparison from other trials in this field. A meta-analysis of eight placebo-controlled trials in female sexual dysfunction found placebo arms improved by 3.62 points on the total FSFI, against 5.35 points in treatment arms [13]. Its authors concluded that 67.7% of the treatment effect was accounted for by placebo [13].
(human) An independent academic re-analyzed both trials using the FDA New Drug Application as his source [3]. He reported that 72.72% of protocol-listed outcomes were not reported by the trial publication, which instead gave 15 secondary measures absent from the protocols [3]. His meta-analysis reproduced results similar to the published ones [3]. He also reported two findings the publication did not. Adverse-event-induced discontinuation on drug against placebo carried an odds ratio of 11.98 (95% CI 3.74 to 38.37, NNH 6) [3]. A composite of completing the trial and electing to enter the open-label extension favored placebo, at an odds ratio of 0.30 (95% CI 0.24 to 0.38, NNH 4) [3]. His stated conclusion is that the drug "is generally not useful" [3].
(human) A follow-up paper recovered the unpublished endpoints. Eight of the 11 efficacy outcomes specified on ClinicalTrials.gov had gone unpublished, including FSDS-DAO total score, FSFI total score and the FSFI arousal domain [4]. When the authors analyzed them, "effect sizes ranged from nil to small" [4]. The same paper reports that the FSFI, its desire domain, the FSDS-DAO and its item 13 have "questionable, at best, validity evidence for women with HSDD" [4]. It found no validity evidence for the categorical responder outcomes published from RECONNECT [4].
There is a circularity behind that last point. (human) The responder thresholds used in RECONNECT were derived in the sponsor's own Phase 2b program [7]. That paper's own limitations section records that the thresholds came from data in the same clinical trial and from a single-blind phase [7]. It also records that several of its analysis types were post hoc [7]. Three of its seven authors were Palatin Technologies employees [7].
The trial group published a rebuttal, and the dispute is unresolved [5]. Its author list is substantially the RECONNECT group and includes two Palatin Technologies employees [5]. That asymmetry is part of the record rather than a detail. Both pivotal publications carry the funding statement "Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc." and name employees of both companies as authors [1][6]. The critical work came from an academic psychology department [3][4]. No industry funding is disclosed for either paper [3][4]. No sponsor-independent replication of the pivotal trials was identified in PubMed and ClinicalTrials.gov searches run on 2 October 2026. A separate company-sponsored Phase 3 bridging trial in 193 premenopausal women in South Korea was completed in May 2023 and has posted no results [26].
(human) An independent 2026 systematic review of 36 studies assessed both drug and non-drug treatments for female sexual dysfunction [12]. In its pooled analysis, bremelanotide improved total FSFI and its desire and arousal subscales [12]. It also found that mindfulness-based cognitive behavioral therapy improved total FSFI and the desire, arousal and orgasm subscales [12]. It records that no study has directly compared cognitive behavioral therapy with pharmacotherapy [12].
(human) A 52-week open-label extension followed the core phase, and all its analyses were descriptive by design [6]. Of 856 eligible patients, 684 enrolled and 272 completed [6]. That is roughly 60% attrition among people already selected for having tolerated 24 weeks. The larger score changes reported there, 1.25 to 1.30 on the FSFI desire domain, come from an uncontrolled study in a survivor population [6]. They are not comparable with the placebo-controlled 0.35 [1][6].
(human) Nausea occurred in 40.0% of treated patients against 1.3% on placebo [2]. Thirteen percent of treated patients required anti-emetic medication [2]. Eight percent discontinued the trials prematurely because of nausea, and no placebo patient did [2]. A randomized Phase 4 study in 228 healthy women tested oral ondansetron given before the drug [2]. The registry record for that ondansetron study describes its 228 participants as premenopausal women aged 18 to 55 [25]. AMAG Pharmaceuticals, then the North American licensee for VYLEESI, sponsored that ondansetron study [17][25]. The label records no significant difference in nausea incidence between the groups [2]. It concludes that pre-treatment with oral ondansetron "does not reduce the incidence of VYLEESI-associated nausea and is not recommended." [2]
(human) Overall discontinuation due to adverse reactions was 18% on drug against 2% on placebo [2]. Flushing occurred in 20.3% against 0.3%, headache in 11.3% against 1.9%, and vomiting in 4.8% against 0.2% [2]. Serious adverse reactions were much less common, at 1.1% against 0.5% [2]. A low serious-event rate and a heavy tolerability burden are both true of this record.
(human) Focal hyperpigmentation scaled sharply with how often the drug was given. It was reported in 1% of patients receiving up to eight doses per month, in a trial population whose median was ten injections across the whole 24 weeks [2]. No placebo-treated patient reported it [2]. The pivotal trials permitted up to twelve doses in a month, and the approved label does not recommend more than eight [2]. The label ties that lower ceiling to the risk of focal hyperpigmentation and to the time per month with raised blood pressure [2]. In another clinical study, 38% of patients developed focal hyperpigmentation after daily dosing for eight days [2]. Among those who continued for eight more consecutive days, a further 14% developed new pigmentary changes [2]. It involved the face, gingiva and breasts, and patients with dark skin were more likely to develop it [2]. The label states that "Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation of VYLEESI." [2]
(human) The label records transient blood pressure and heart rate changes after each dose [2]. Maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after dosing, with heart rate falling by up to 5 beats per minute [2]. Values usually returned to baseline within 12 hours [2]. The product is not recommended for patients at high risk for cardiovascular disease [2].
(human) One case of acute hepatitis appears in the label. The patient had received 10 doses over one year [2]. She presented with serum transaminases above 40 times the upper limit of normal, and total bilirubin 6 times that limit [2]. Liver tests returned to normal 4 months after the drug was stopped [2]. The label states that "Because another etiology was not identified, the role of VYLEESI could not definitively be excluded." [2] It adds that there was no imbalance between treatment groups in transaminase outliers [2]. One labeled case is not a signal.
(animal) Reproductive toxicity is on the label. Daily subcutaneous dosing of pregnant dogs during organogenesis produced fetal harm at exposures at or above 16 times the maximum recommended human dose by AUC [2]. Developmental effects appeared in mouse offspring at 125 times the maximum recommended human dose by AUC and above [2]. The lowest harmful dose was not identified in either species [2]. The label requires effective contraception and discontinuation if pregnancy is suspected [2].
(human) Two drug interactions are labeled. Bremelanotide may slow gastric emptying and reduce absorption of oral medicines that depend on threshold concentrations [2]. It may also significantly decrease systemic exposure to orally administered naltrexone, which the label says to avoid because of the severe consequence of naltrexone treatment failure [2].
Bremelanotide is not approved for men in the United States. The label's Limitations of Use bar that use explicitly [2]. No central EU authorization and no Canadian authorization were found [21].
On 30 August 2007, Palatin and King Pharmaceuticals announced that they "have delayed plans for the initiation of Phase 3 clinical trials with bremelanotide" for male erectile dysfunction [16]. The release states that FDA "raised serious concerns about the acceptable benefit/risk ratio" for a Phase 3 program in that indication [16]. It adds that FDA "questioned the overall efficacy results and the clinical benefit of this product in both the general and diabetic ED populations" [16]. FDA also "cited blood pressure increases as its greatest safety concern" [16]. The same release records FDA's stated alternative [16]. FDA "was amenable to proposals for a different drug development pathway, such as for a second-line therapy in non-responders to currently approved PDE-5 inhibitors" [16]. The Phase 1 and Phase 2 work behind that program used an intranasal route, which is not the route later approved [9][14].
(human) The largest randomized bremelanotide trial in men is not safely citable. A 2008 trial in 342 men with sildenafil-non-responsive erectile dysfunction carries a formal Expression of Concern, published by its journal in January 2023 [10][11]. That action is not isolated. A PubMed query for the same author returns 14 records typed as Expression of Concern and 18 typed as Retracted Publication [22].
The male program is not dead, and it is also not evidence. Palatin's annual report for the fiscal year ended 30 June 2025 lists a bremelanotide and PDE5 inhibitor co-formulation for men not adequately responsive to PDE5 inhibitor monotherapy [18]. The same filing places that candidate among products in the early stages of development [18]. No approval and no published controlled efficacy result follow from a pipeline listing.
Commercial ownership of the product has moved more than once. AMAG Pharmaceuticals licensed North American rights in January 2017 [17]. It launched the product nationally in September 2019 [24]. It terminated that license in July 2020 [17]. AMAG paid Palatin $12 million at closing plus $4.3 million the following March to return the asset [17]. That exit came roughly ten months after the launch [17][24]. Cosette acquired the product in December 2023 and is the current sponsor of record [14][18].
(human) The first published proof-of-concept study in women used a single intranasal dose in 18 premenopausal women with sexual arousal disorder [8]. More women reported moderate or high sexual desire after the drug than after placebo, at P = 0.0114 [8]. Among those who attempted intercourse within 24 hours, significantly more were satisfied with their level of arousal, at P = 0.0256 [8]. Genital arousal was a non-significant trend, at P = 0.0833 [8]. The objective measure failed, in that vaginal vasocongestion did not change significantly compared with placebo [8]. Three of the six authors, including the corresponding author, were Palatin Technologies employees [8].
FDA has named bremelanotide in a compounding enforcement action. A 2020 warning letter to a compounding firm names "Bremelanotide (PT-141)" among substances whose compounded products "are not eligible for the exemptions provided by section 503A(a)" [20]. The inspection behind that letter ran from 20 August to 24 October 2018 [20]. That predates the June 2019 approval, so the letter's stated reasoning reflects the pre-approval position [14][20]. The letter shows that FDA has acted on compounded bremelanotide. It does not state the substance's current compounding status.
PT-141 is bremelanotide, and bremelanotide holds a real, current US approval. That approval covers premenopausal women with a diagnosed case of acquired, generalized HSDD, in a prescription subcutaneous autoinjector [2][14]. The same label states that the product is not indicated in men, not indicated in postmenopausal women, and not indicated to enhance sexual performance [2]. Its measured effect on desire in the pivotal trials was statistically significant [1]. That effect was a placebo-subtracted 0.35 points on a desire scale running from 1.2 to 6.0 [1][2]. Its most common adverse reaction was nausea, in 40% of treated patients [2].
Bremelanotide is approved in the United States as VYLEESI, NDA 210557, a prescription subcutaneous autoinjector. The approval covers premenopausal women with acquired, generalized HSDD that is not due to a co-existing condition, relationship problems or another medication. The label states that it "is not indicated for the treatment of HSDD in postmenopausal women or in men" and "is not indicated to enhance sexual performance".
No. CAS 189691-06-3 resolves to bremelanotide free base, CID 9941379. The approved product contains bremelanotide acetate, CAS 1607799-13-2, CID 91971505. The catalogue does not state whether the research powder is the free base or a salt, so the free-base CAS identifies the peptide rather than confirming the powder's form.
No. PubChem lists them as separate records, and bremelanotide is the deamidated form. Their regulatory positions run in opposite directions. Melanotan II has no US approval and appears on FDA's page of bulk substances that may present significant safety risks, among those whose category 2 nominations were withdrawn, and neither "bremelanotide" nor "PT-141" appears on that page.
No sponsor-independent replication of the pivotal trials was identified; a company-sponsored Phase 3 bridging trial in South Korea was completed in 2023 but has posted no results. Both were funded by Palatin Technologies and AMAG Pharmaceuticals, and both name employees of those companies as authors. An independent re-analysis using the FDA New Drug Application reproduced similar results, and reported unpublished outcomes on which "effect sizes ranged from nil to small". The trial group published a rebuttal, and the dispute is unresolved.
References
Reviewed for scientific accuracy
Dr. Martina Rossi, PhD
PhD, Université Grenoble Alpes · Scientific Contributor and Reviewer
Dr. Rossi's doctoral research at Université Grenoble Alpes examined the vascular functions of bone morphogenetic proteins. Her peer-reviewed work spans cell and molecular biology, vascular biology, and gene therapy, in journals including Cardiovascular Research, Scientific Reports, and Brain Sciences. She reviews Pure Peptides' product, reference, and research pages for scientific accuracy against the sources they cite.
PT-141 and melanotan II get treated as near-enough the same thing. FDA's compounding safety-risk page names only melanotan II, as a withdrawn nomination.
PTD-DBM is a CXXC5-blocking peptide studied in cells and mice for wound healing and hair regrowth. ClinicalTrials.gov lists no human trial of it.
An evidence-led review of VIP and aviptadil research: regulatory status stated precisely, the COVID-19 and ARDS trials, and the erectile dysfunction evidence.
An evidence-led review of oxytocin research: regulatory status, the delivery question, the autism trials, and the trust and social cognition literature.
An evidence-led review of kisspeptin-10 research: its mechanism, the human studies, why the evidence in women is inconsistent, and what it does not show.
An evidence-led review of ACTH 1-39 research: what it is, the molecules it is not, how it acts, and its regulatory status in the United States.
A receptor-biology look at Melanotan 2 research: peptide structure, melanocortin receptor agonism, and preclinical findings on the MC1R, MC3R, MC4R, and MC5R subtypes.
