What it is
PT-141, generic name bremelanotide, is a small lab-made peptide of seven amino acids, six of them joined in a ring. It is almost identical to Melanotan II, differing only in one chemical group at the end of the chain. Like Melanotan II, it switches on melanocortin receptors, a family of receptors found on pigment cells in the skin and on nerve cells in the brain.
The approved product, Vyleesi, is a single-dose autoinjector for injection under the skin on an as-needed basis. It is approved in the United States for one thing: low sexual desire that causes distress in women who have not been through menopause, when the problem is not explained by another condition, a relationship problem or a medicine. How it works for that purpose is not known.
Bremelanotide (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, C50H68N14O10, 1025.2 g/mol free base) is the C-terminal carboxylic acid counterpart of Melanotan II. The label describes it as a non-selective melanocortin receptor agonist with an order of potency MC1R, MC4R, MC3R, MC5R, MC2R, and states that MC1R and MC4R binding is most relevant at therapeutic doses. MC4R is widely expressed in the central nervous system, including hypothalamic circuits linked to sexual motivation; the label states that the mechanism in HSDD is unknown. MC1R activation on melanocytes accounts for the focal hyperpigmentation.
Pharmacokinetics (label): after 1.75 mg subcutaneously, mean Cmax 72.8 ng/mL and AUC 276 h·ng/mL, median Tmax about 1 hour, absolute bioavailability about 100%, 21% protein binding, volume of distribution about 25 L, and mean terminal half-life about 2.7 hours. Elimination is by hydrolysis of amide bonds; 64.8% of a radiolabelled dose was recovered in urine and 22.8% in faeces.
Who made it and when
Bremelanotide grew out of the University of Arizona’s Melanotan II work, where researchers noticed that men given the tanning compound had unexpected erections. Palatin Technologies patented bremelanotide in 1999 and first tested it as a nasal spray in men with erectile problems.
Development later moved to women and to an injection under the skin. Palatin ran the two main trials, then licensed North American rights to AMAG Pharmaceuticals in 2017. The FDA approved Vyleesi on 21 June 2019. AMAG handed the rights back to Palatin in 2020, and in December 2023 Palatin sold the product to Cosette Pharmaceuticals, which holds the approval today.
US 6,579,968 (priority June 1999, granted June 2003, assigned to Palatin) claims Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH and its salts for sexual dysfunction; it has expired. Early clinical work used intranasal PT-141: Diamond et al. (Int J Impot Res 2004) reported median Tmax 0.5 hours, half-life 1.85–2.09 hours, and significant erectile responses above 7 mg in healthy men and sildenafil-responsive men with erectile dysfunction. The programme later switched to subcutaneous dosing in premenopausal women; a randomised, placebo-controlled dose-finding trial in premenopausal women (Clayton et al., Womens Health 2016) preceded Phase 3.
Palatin sponsored the two identical Phase 3 RECONNECT trials (Studies 301 and 302), started January 2015. AMAG obtained exclusive North American rights in 2017 and filed the NDA; FDA approved NDA 210557 on 2019-06-21 as a new molecular entity. The AMAG agreement ended in 2020, and Palatin completed the sale of Vyleesi to Cosette for USD 12 million upfront plus sales milestones in December 2023. Drugs@FDA lists Cosette as the application holder.
What the data say
Two matched trials enrolled about 1,270 premenopausal women with long-standing low desire. Over 24 weeks, women using Vyleesi reported a small increase in desire and a small decrease in distress about low desire compared with placebo. On the desire scale used, which runs from 1.2 to 6, the average extra improvement over placebo was about a third of a point. Most women in the trials used it two or three times a month.
Side effects were common. Four in ten had nausea, typically starting within an hour of a dose and most often after the first dose, and about one in five had flushing. Blood pressure rose briefly after each dose. With frequent use, some women developed dark patches on the face, gums or breasts that did not always fade.
RECONNECT (Kingsberg et al., Obstet Gynecol 2019): 1,267 women randomised 1:1 to bremelanotide 1.75 mg subcutaneously as needed or placebo for 24 weeks; 1,247 in the safety and 1,202 in the modified intent-to-treat population; mean age 39, 85.6% white, 96.6% at US sites. Co-primary endpoints were change in the FSFI desire domain (range 1.2–6.0) and FSDS-DAO item 13 (range 0–4). Treatment differences for desire were +0.30 (Study 301) and +0.42 (Study 302), integrated +0.35 (all P under .001); for distress −0.37 (P under .001) and −0.29 (P=.005), integrated −0.33. The label reports no difference from placebo in the number of satisfying sexual events, a secondary endpoint, and more early discontinuation on bremelanotide.
Safety (label, n=627 vs 620): nausea 40.0% vs 1.3%, flushing 20.3% vs 0.3%, injection-site reactions 13.2% vs 8.4%, headache 11.3% vs 1.9%, vomiting 4.8% vs 0.2%. Blood pressure rose by up to 6/3 mmHg, peaking 2–4 hours after dosing and returning to baseline within about 12 hours. Focal hyperpigmentation occurred in 1% at up to 8 doses a month and 38% after 8 consecutive daily doses. The label advises stopping after 8 weeks if there is no improvement.
Regulatory picture
Three separate facts. Approval: bremelanotide is FDA approved as Vyleesi, for premenopausal women with acquired, generalized HSDD only. The label says it is not approved for women after menopause, for men, or to enhance sexual performance. Compounding: because an approved product exists, pharmacies may not make copies of it. As an ingredient of an approved drug it can legally be used by a US pharmacy in a patient-specific preparation that is not a copy, but such preparations are not reviewed by the FDA. Enforcement: in August 2026 the FDA sent warning letters to online sellers of “research” peptides that listed PT-141, saying the products were unapproved drugs meant for people. Products sold online as PT-141 are not Vyleesi.
Approval: approved. NDA 210557, approved 2019-06-21; label revised 10/2020. Limitations of use: not indicated in postmenopausal women or men, or to enhance sexual performance. The label contraindicates it in uncontrolled hypertension or known cardiovascular disease, advises against it in patients at high cardiovascular risk, and states that no more than one dose should be given in 24 hours and that more than 8 doses a month is not recommended.
Compounding: recorded as restricted, meaning copies of Vyleesi are not permitted. Because bremelanotide is a component of an FDA-approved drug, section 503A allows it as a bulk ingredient for patient-specific preparations that are not essentially copies; those preparations are not FDA-reviewed. It is not among the substances FDA placed in Category 2.
Enforcement: FDA warning letters dated 2026-08-24 to online peptide sellers named PT-141 (bremelanotide) among unapproved new drugs, rejecting “research use only” labelling where websites made human-use claims. No FDA action against the approved product has been reported.
