PT-141 (bremelanotide): what the molecule is, what the trials measured, and what its FDA label and COA say

What PT-141 is: a cyclic melanocortin-receptor agonist#

PT-141 is the development code for bremelanotide, a synthetic cyclic heptapeptide modeled on alpha-melanocyte-stimulating hormone (alpha-MSH), the pituitary peptide that signals through the melanocortin receptor family. The FDA label describes bremelanotide as a melanocortin receptor agonist that activates several receptor subtypes rather than one ^[1]. The developer's 2003 pharmacology paper describes PT-141 as a synthetic analogue of alpha-MSH acting as an agonist at melanocortin receptors expressed mainly in the central nervous system, in particular MC3R and MC4R ^[2].

The molecule is closely related to melanotan II (MT-II). Melanotan II has the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2: a six-residue ring closed between the side chains of aspartate and lysine, an acetylated norleucine at the N-terminus and an amide at the C-terminus ^[9]. Bremelanotide, as described in the Vyleesi label, is Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys)-OH: the same N-terminus and ring, but a free carboxylic acid at the C-terminus in place of the amide ^[1]. That single change at the end of the chain is the structural difference between the two peptides, which otherwise have separate literatures and separate regulatory histories.

PT-141 sequence, molecular weight, formula and CAS number#

Identifiers for the free peptide: molecular formula C50H68N14O10, molecular weight 1,025.2 g/mol, CAS registry number 189691-06-3, PubChem CID 9941379; the monoisotopic mass in PubChem is 1,024.52 Da ^[1][10]. The drug substance in Vyleesi is the acetate salt, which weighs more per mole than the free peptide ^[1]. A COA's measured content is in milligrams of material, and the report should say whether it was corrected for counter-ion and water.

Receptor pharmacology: MC1R, MC3R and MC4R#

The five melanocortin receptors (MC1R to MC5R) are G-protein-coupled receptors with different tissue distributions: MC1R on pigment cells, MC2R as the ACTH receptor in the adrenal cortex, MC3R and MC4R largely in the brain. The Vyleesi label gives bremelanotide's order of potency as MC1R, then MC4R, MC3R, MC5R and MC2R, and says binding to MC1R and MC4R is the most relevant at the exposures reached in the clinical program ^[1]. The 2003 pharmacology paper emphasizes the two central receptors, MC3R and MC4R, as the targets for the behaviors studied in animals ^[2].

Two consequences follow from that profile. Because the compound is potent at MC1R, the receptor that drives melanin production, pigmentation changes are part of its documented record: the label reports focal hyperpigmentation as an adverse reaction ^[1]. Because MC4R-expressing neurons are present across the central nervous system, the compound's behavioral effects in animals are attributed to central rather than peripheral action ^[1][2]. The label is explicit that the mechanism by which bremelanotide acts in its approved indication is unknown ^[1].

Preclinical studies: what was measured in animals#

The published preclinical literature on PT-141 is small and comes mostly from the developer's group. Molinoff and colleagues (2003) report that systemic PT-141 produced penile erections in rats and in nonhuman primates, increased c-Fos immunoreactivity (a marker of neuronal activation) in a hypothalamic region, and that neurons in that region took up a tracer virus placed in the corpus cavernosum, which the authors read as evidence of a neural pathway between the hypothalamus and the erectile response ^[2]. Work with the parent compound MT-II in Long-Evans rats showed that erections followed delivery to the brain ventricles, to the lumbosacral spinal cord or intravenously, that spinal delivery was the most effective, that the antagonist SHU-9119 blocked the spinal response, and that delivery into the penis itself did not raise intracavernous pressure, arguing against a direct peripheral site of action ^[9].

The one widely cited female-animal study is Pfaus and colleagues, PNAS 2004. Hormone-primed female Long-Evans rats were tested in pacing chambers after PT-141, scoring solicitations, hops and darts, pacing, lordosis quotient, female mounting, the male's return latencies, open-field locomotion and conditioned place preference. PT-141 increased solicitational behaviors at the two higher amounts tested without changing lordosis or pacing, and without general motor activation or any change in the conditioned-reward measure ^[3]. The authors read that selectivity as evidence that central melanocortin systems act on appetitive rather than reflexive components of sexual behavior in the rat.

The early human studies and the discontinued intranasal program#

Bremelanotide's first clinical program was in men, using an intranasal formulation. Diamond and colleagues (2004) reported double-blind, placebo-controlled studies of intranasal PT-141 in healthy men and in men with mild-to-moderate erectile dysfunction who responded to sildenafil. Erectile activity was measured with a RigiScan device, without visual sexual stimulation in healthy subjects and with it in patients. Plasma concentration rose with the amount given, median time to peak was 0.5 hours, mean half-life was 1.85 to 2.09 hours, and flushing and nausea were the most common adverse events ^[4]. A companion paper by Rosen and colleagues studied a subcutaneous formulation in healthy men and in men with an inadequate response to sildenafil, using a crossover design and the same RigiScan outcome ^[5]. Neither abstract reports participant numbers.

The intranasal program did not continue. In the summer of 2007 the FDA raised questions about increases in blood pressure seen with the nasal formulation, development was halted, and the commercial partner withdrew. In May 2008 Palatin Technologies announced that it was ending work on intranasal bremelanotide for male sexual dysfunction and reducing staff ^[6]. The blood-pressure finding carried through to the approved product: the current label lists uncontrolled hypertension or known cardiovascular disease as a contraindication and describes a transient rise in blood pressure with a fall in heart rate after each administration ^[1].

Regulatory status: Vyleesi and its label#

The FDA approved bremelanotide in 2019 under the brand name Vyleesi, held by Palatin Technologies. The label states that the product is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems with the relationship, or the effects of a medication or drug substance ^[1]. The limitations of use state that the product is not indicated for HSDD in postmenopausal women or in men, and is not indicated to enhance sexual performance ^[1]. Those two sentences define the entire scope of the approval.

The label's safety sections are part of the compound's documented record. The contraindication is uncontrolled hypertension or known cardiovascular disease. The warnings cover a transient increase in blood pressure with a reduction in heart rate, focal hyperpigmentation, and nausea. The most common adverse reactions in the Phase 3 program, with placebo rates in parentheses, were nausea 40.0% (1.3%), flushing 20.3% (0.3%), reactions at the administration site 13.2% (8.4%), headache 11.3% (1.9%) and vomiting 4.8% (0.2%); 18% of participants on bremelanotide discontinued because of adverse reactions against 2% on placebo ^[1]. Focal hyperpigmentation was reported in 1% of trial participants, was more frequent in those with darker skin, and did not resolve in all cases ^[1]. These are a regulator's findings about a drug product, listed here as part of the record, not as guidance.

The label's pharmacokinetics section records a mean terminal half-life of about 2.7 hours and metabolism by hydrolysis of the peptide's amide bonds ^[1]. The label version read for this article has an effective date of January 10, 2025; the original 2019 label is listed on the product page.

The RECONNECT Phase 3 trials: what was measured#

The approval rested on two identical randomized, double-blind, placebo-controlled trials, studies 301 and 302, run under the name RECONNECT and reported together by Kingsberg and colleagues in Obstetrics & Gynecology in 2019 ^[7]; a 52-week open-label extension was reported in the same issue by Simon and colleagues ^[8]. Our guide to reading published peptide research explains the study types.

Points to keep in mind: the population was narrow (premenopausal women, mean age 39, 85.6% white, 96.6% at U.S. sites) ^[7]; the co-primary endpoints were patient-reported questionnaire scores, and the between-group differences, while statistically significant, were a fraction of a point on each scale ^[7]; the label reports the same endpoints as absolute changes of 0.5 versus 0.2 and 0.6 versus 0.2 (FSFI desire) and -0.7 versus -0.4 (FSDS-DAO item 13) ^[1]; and the extension had no placebo arm, so its figures are descriptive ^[8].

What the research does not cover#

• Postmenopausal women and men, in the approved indication. The label states the product is not indicated for either group ^[1]; the male program ended before Phase 3 ^[6].
• Any outcome other than the two questionnaire endpoints. RECONNECT measured desire and distress scores, not hormones, imaging or long-term health outcomes ^[7].
• Durability beyond 76 weeks in total (24 double-blind plus 52 open-label) ^[8].
• Independent receptor data. Binding and potency statements come from the label and the developer's 2003 paper ^[1][2].
• Head-to-head comparison with melanotan II. The structural relationship is documented; no study cited here compares the two directly ^[1][9].
• Preclinical work outside sexual-behavior models. The published animal work on PT-141 concerns erectile and solicitational behavior in rats and primates ^[2][3].

Anti-doping status#

Bremelanotide is not named in the 2026 WADA Prohibited List, and neither is melanotan or the melanocortin receptor class ^[11]. The list's S0 category prohibits any pharmacological substance not covered elsewhere on the list and with no current approval by any governmental regulatory health authority for human therapeutic use; because bremelanotide has an FDA approval, it does not fall under S0 either, whereas melanotan II, with no approval anywhere, would ^[11]. Absence from the list is not a clearance, and anyone handling this material in a sport context should check with their anti-doping organization.

Reading a PT-141 Certificate of Analysis#

Renuvia's current PT-141 lot, VB-2609-01-DM, carries a supplier-provided certificate rather than one commissioned by Renuvia. The certificate is from KMD Analytical, dated October 7, 2026, and reports an HPLC-DAD purity of 99.68%, identity confirmed, and a measured content of 10.55 mg in a vial labeled 10 mg (105.5% of label) ^[12]. It is filed in the COA library and labeled as supplier-provided. Renuvia's own lots are tested by Freedom Diagnostics Testing (HPLC-UV purity, LC-MS identity, measured content); a supplier certificate is the supplier's statement until a third-party report replaces it. Our guides to verifying that a COA is genuine and to vetting a research peptide supplier explain the difference.

When you read any PT-141 certificate, check these points:

1. The mass spectrometry result should match bremelanotide, about 1,025 Da for the free peptide (monoisotopic 1,024.52), not melanotan II. The two differ by about one mass unit at the C-terminus (NH2 against OH), so a mass rounded to the nearest 10 Da cannot distinguish them. Ask for the observed mass to at least one decimal place, or a retention-time match against a reference standard.
2. The purity figure should come from a chromatographic method (HPLC-UV or HPLC-DAD) with the chromatogram attached, so you can see whether adjacent peaks were quantified or folded into one rounded figure. Our peptide purity guide explains why 99% on paper can mean different things.
3. The measured content, in milligrams, should be stated separately from the purity percentage. A 10 mg label with 10.55 mg measured is a content statement; it says nothing about purity, and purity says nothing about content.
4. The lot number should match the vial, the laboratory should be named with a report number, and the certificate should say who commissioned it. A supplier-provided certificate tests the supplier's material, not necessarily the vialed lot you hold.
5. Because the peptide is cyclic, a ring-opened hydrolysis impurity has a mass about 18 Da above the parent; the label notes hydrolysis of the amide bonds as the main metabolic route ^[1]. A peak at parent mass plus 18 should be quantified, not ignored.

The guides to reading a Certificate of Analysis and HPLC and mass spectrometry cover each section of a report.