PT-141 (Bremelanotide) Research: The Cyclic Melanocortin Heptapeptide and What Studies Have Investigated

What is PT-141 (bremelanotide)?

What is PT-141? As a molecule it is a cyclic heptapeptide: seven residues closed into a macrocycle by a lactam bridge, with an acetylated norleucine at the N-terminus and a free carboxylic acid at the C-terminus — written in the chemical literature as Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH. The ring forms between the aspartate and lysine side chains rather than by a disulfide bond, which constrains the conformation and resists the exopeptidases that clip linear peptides from their ends.

Two features carry its identity: the His-D-Phe-Arg-Trp core, the message sequence conserved across the melanocortin peptides with the phenylalanine inverted to the D-configuration; and the free-acid C-terminus, which distinguishes bremelanotide in the chemical record from its carboxamide-terminated relative melanotan-2.

Discovery and origin in the literature

The α-MSH lineage

Bremelanotide belongs to a family of synthetic analogues built from α-melanocyte-stimulating hormone, a thirteen-residue peptide whose central His-Phe-Arg-Trp motif is the minimal sequence the melanocortin receptors recognise. Medicinal-chemistry work through the 1980s and 1990s established that inverting that phenylalanine and cyclising the backbone produced analogues both more potent at the receptors and far more stable than the native hormone. Molinoff and colleagues at Palatin Technologies described PT-141 in Annals of the New York Academy of Sciences in 2003 (PMID 12851303) as “a synthetic peptide analogue of alpha-MSH” acting as an agonist at melanocortin receptors including MC3R and MC4R.

Amide versus acid, and regulatory status

The chemical record makes the relationship between the two related compounds unusually clean. Melanotan-2 is PubChem CID 92432, C₅₀H₆₉N₁₅O₉, ≈ 1024.2 Da; bremelanotide is CID 9941379, C₅₀H₆₈N₁₄O₁₀, ≈ 1025.2 Da. One nitrogen replaced by one oxygen — the conversion of a terminal carboxamide to a terminal carboxylic acid — with an identical macrocycle shared between them. Roughly one mass unit separates the two, which places a real demand on the mass spectrometry used to tell them apart. Bremelanotide is also the active ingredient of an approved prescription product (Vyleesi), authorised in the United States in 2019. A licensed finished pharmaceutical and a characterised research chemical are different categories of material, held to different standards, and are not interchangeable.

Reference data

The molecule facts below are drawn from the public chemical record (PubChem CID 9941379). They describe identity and physical form only.

Solubility is deliberately omitted rather than asserted: a value we cannot source from the public record is a value we will not print. No reconstitution procedure, quantity or route is given or implied.

Mechanisms researchers have examined

The PT-141 mechanism literature is melanocortin-receptor pharmacology. Each point below is what studies characterise in model systems:

• The melanocortin receptor family — five class-A G-protein-coupled receptors, MC1R through MC5R, reviewed by Cone in Endocrine Reviews in 2006 (PMID 17077189). They differ from one another in tissue distribution and ligand selectivity.
• Gs–adenylyl cyclase coupling — that literature describes the melanocortin receptors as coupling principally to Gs, stimulating adenylyl cyclase and raising intracellular cyclic AMP in the cell systems studied.
• MC3R and MC4R as the relevant subtypes — Molinoff et al. (2003) reported PT-141 as an agonist at receptors including MC3R and MC4R, subtypes described as expressed primarily in the central nervous system. Receptor selectivity, not potency alone, is the recurring question here.
• Central neuronal mapping in animal models — the same report described systemic PT-141 in rats increasing c-Fos immunoreactivity in hypothalamic neurons. c-Fos is a standard immediate-early-gene marker for identifying which neuronal populations a compound engages; it is reported here as methodology.

What the published clinical program measured

Because bremelanotide progressed to a licensed product, its trial record is public. The following states what was measured, by whom and under what registration — attributed throughout, offered as bibliography rather than as any claim by us.

• Phase-2 dose-finding — Clayton and colleagues reported a randomised, placebo-controlled dose-finding trial in premenopausal women in Women’s Health (London) in 2016 (PMID 27181790), the study preceding the phase-3 program.
• The RECONNECT phase-3 pair — Kingsberg et al., Obstetrics & Gynecology, 2019 (PMID 31599840): two identical randomised, double-blind, placebo-controlled multicentre trials, registered as NCT02333071 and NCT02338960, sponsored by Palatin Technologies, Inc. and AMAG Pharmaceuticals, Inc. Of 1,267 participants randomised, 1,247 were in the safety population and 1,202 in the modified intent-to-treat efficacy population; mean age was 39 years and 96.6% of sites were in the United States.
• The instruments used — coprimary endpoints were change from baseline to end of study in the Female Sexual Function Index desire-domain score and in item 13 of the Female Sexual Distress Scale — Desire/Arousal/Orgasm. Both are validated self-report questionnaires; naming them describes trial methodology.
• Reported tolerability — the authors reported nausea, flushing and headache each in 10% or more of participants in both studies, more frequently than with placebo. Reported for completeness, without interpretation.
• Open-label extension — Simon et al. published a longer-term safety and efficacy report in the same 2019 issue (PMID 31599847).

Research models and evidence status

The melanocortin analogue literature is a mature medicinal-chemistry and receptor-pharmacology field, and the bremelanotide trial record is a public, industry-sponsored, single-indication program in one population.

What is not established, and is deliberately not claimed here: any property of the supplied research material in a person. The published trials studied a licensed finished pharmaceutical administered under a marketing authorisation in a controlled clinical setting — a different object from a characterised research chemical in a vial. The endpoints were validated questionnaire scores in a specified diagnostic population and transfer to nothing else. The trials were sponsored by the companies developing the compound, noted here because disclosed funding is part of reading a trial honestly. Beyond the receptor-level work, the mechanistic account linking melanocortin signalling to what those questionnaires measured remains incomplete. This page therefore makes no efficacy, therapeutic, behavioural or other use claim of any kind, and the material is supplied for laboratory research use only — not for human or veterinary use.

How to verify this compound yourself

For a constrained macrocyclic peptide, identity and purity rest on two orthogonal analytical methods, both of which appear on a per-batch Certificate of Analysis:

• HPLC purity — reversed-phase chromatography separates the target peptide from related impurities and reports purity as a percentage of the chromatogram. For a cyclic peptide, ring-opened and partially cyclised species are exactly what this method is meant to resolve.
• Mass-spec identity — mass spectrometry confirms the measured mass against the expected ≈ 1025 Da. This is the check that matters most here: carboxamide-terminated melanotan-2 sits about one mass unit away at ≈ 1024 Da, so adequate mass resolution is what distinguishes the two compounds analytically.
• Endotoxin and sterility — where tested, separate quality attributes reported in EU/mL or as a sterility result, independent of chemical purity.

See how to read a COA for what each certificate line means, and how to verify peptide purity for how the two methods fit together. The exact batch received can be checked on the self-serve verify tool.

Research-grade sourcing and verification

PT-141 is not held in stock. It is listed on our sourcing catalogue as available to order — our supplier lists it, we have not bought it, and material of this kind typically takes about two to three weeks to reach us. For laboratory research use only, it is supplied with a per-batch Certificate of Analysis reporting HPLC purity (%) and mass-spec identity confirmation, verifiable at the lot level. This is sourcing and quality-assurance framing only.

Frequently asked questions

Literature cited

1. Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. “PT-141: a melanocortin agonist for the treatment of sexual dysfunction.” Ann N Y Acad Sci. 2003;994:96–102. PMID 12851303. pubmed.ncbi.nlm.nih.gov/12851303.
2. Cone RD. “Studies on the physiological functions of the melanocortin system.” Endocr Rev. 2006;27(7):736–749. PMID 17077189. pubmed.ncbi.nlm.nih.gov/17077189.
3. Clayton AH, Althof SE, Kingsberg S, et al. “Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.” Womens Health (Lond). 2016;12(3):325–337. PMID 27181790. pubmed.ncbi.nlm.nih.gov/27181790.
4. Kingsberg SA, Clayton AH, Portman D, et al. “Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials.” Obstet Gynecol. 2019;134(5):899–908. PMID 31599840. pubmed.ncbi.nlm.nih.gov/31599840.
5. Simon JA, Kingsberg SA, Portman D, et al. “Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder.” Obstet Gynecol. 2019;134(5):909–917. PMID 31599847. pubmed.ncbi.nlm.nih.gov/31599847.
6. ClinicalTrials.gov. “Study BMT-301 (RECONNECT),” NCT02333071, Palatin Technologies, Inc. clinicaltrials.gov/study/NCT02333071.
7. ClinicalTrials.gov. “Study BMT-302 (RECONNECT),” NCT02338960, Palatin Technologies, Inc. clinicaltrials.gov/study/NCT02338960.
8. National Center for Biotechnology Information. “PubChem Compound Summary for CID 9941379, Bremelanotide.” pubchem.ncbi.nlm.nih.gov/compound/9941379 (formula, mass, CAS 189691-06-3). Melanotan-2 comparison data from CID 92432.