Research library
PT-141 Research Overview: Melanocortin Receptor Pharmacology and Randomised Trial Evidence
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- Peptide Pilots Scientific Content Team
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- Peptide Pilots Quality & Compliance review
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What is the controlled human evidence behind PT-141, and what were the safety findings that shaped its approved use?
PT-141 (bremelanotide) is a cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that acts as a non-selective melanocortin-receptor agonist, with activity at MC4R implicated in its central effects on sexual desire. It was originally investigated as a subcutaneous on-demand treatment for both female and male sexual dysfunction; male-indication development (erectile dysfunction) was discontinued after a co-occurring blood-pressure signal, while two randomised phase 3 trials in premenopausal women with acquired, generalised hypoactive sexual desire disorder (HSDD) reported statistically significant increases in desire and reductions in distress, supporting its 2019 FDA approval as Vyleesi. Nausea and transient blood-pressure elevation are the recurring, dose-limiting findings across the programme.
This page is an educational literature summary for laboratory professionals. It is not medical advice, not a description of product performance, and it does not describe or endorse human or veterinary use. Materials referenced are supplied for controlled laboratory research only.
What is PT-141 (Bremelanotide)?
Alpha-MSH and related melanocortin peptides act on a family of five melanocortin receptors (MC1R-MC5R) that regulate pigmentation, energy homeostasis, and, via central MC4R signalling, appetite and sexual function.
PT-141 is a metabolite of the earlier compound melanotan II, in which the C-terminal region was truncated and modified to retain melanocortin-receptor agonism while altering the balance of receptor subtype activity relative to the parent compound.
PT-141 (Bremelanotide) names and identifiers
Also referred to as: Bremelanotide; PT-141; Vyleesi (approved product name)
| Sequence | Cyclic heptapeptide: Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH |
|---|---|
| Molecular formula | C50H68N14O10 |
| Average molecular weight | ≈1025.2 g/mol |
| CAS number | 189691-06-3 |
| Molecular target | Melanocortin receptors, principally MC4R (UniProt P32245), with activity also at MC1R |
| Regulatory status | FDA-approved as Vyleesi (subcutaneous injection) in 2019 for acquired, generalised HSDD in premenopausal women |
PT-141 (Bremelanotide) research background
Melanotan II, a cyclic melanocortin agonist developed to study tanning and appetite pathways, was observed in an early-phase human trial to produce spontaneous erections in male volunteers, prompting a targeted development programme for sexual dysfunction.
PT-141 was derived from melanotan II by removing the C-terminal residues, yielding a linear-cyclic heptapeptide with a distinct receptor activity profile and a formulation initially explored as an intranasal spray before moving to subcutaneous autoinjector delivery.
Male erectile-dysfunction development was discontinued in 2008 after a phase 2a trial identified a dose-related increase in blood pressure that raised concern for the intended repeat-use population; development was redirected to female HSDD, culminating in the phase 3 RECONNECT trials and 2019 approval.
Proposed PT-141 (Bremelanotide) mechanisms and pathways
Evidence is separated by study type. In-vitro and animal findings describe model systems and do not establish equivalent behaviour in humans.
PT-141 (Bremelanotide) in-vitro and cell-based evidence
- Acts as a non-selective agonist across the melanocortin receptor family, with reported nanomolar potency at MC4R and MC1R in transfected cell-based cAMP assays.
- MC4R is expressed in hypothalamic and other central circuits implicated in the regulation of sexual arousal and food intake, providing the pharmacological rationale for a central, rather than local vascular, mechanism of action distinct from PDE5 inhibitors.
PT-141 (Bremelanotide) animal-model evidence
- Rodent studies report that central and peripheral melanocortin-receptor agonism increases measures of sexual behaviour (e.g. mounting frequency, genital reflexes) in both sexes, supporting a central pro-sexual mechanism.
- Animal cardiovascular studies confirm dose-related increases in blood pressure and heart rate consistent with melanocortin receptor effects on the sympathetic nervous system, informing later human dose selection.
Published PT-141 (Bremelanotide) human-study evidence
- The two identically designed phase 3 RECONNECT trials in premenopausal women with acquired, generalised HSDD reported statistically significant increases in the Female Sexual Function Index desire domain and reductions in FSDS-DAO distress scores versus placebo over 24 weeks of as-needed use.
- A thorough QT and cardiovascular pharmacology study in healthy volunteers reported transient increases in blood pressure and reflex reductions in heart rate following subcutaneous dosing, findings reflected in the approved product's prescribing information as a contraindication in uncontrolled hypertension and cardiovascular disease.
- Nausea was the most commonly reported adverse event across the programme, generally more frequent with early or repeated dosing, alongside flushing and injection-site reactions.
Published PT-141 (Bremelanotide) studies
| Study | Model / type | Research question | Main observation | Citation |
|---|---|---|---|---|
| Clayton et al., RECONNECT phase 3 programme | Human, two identically designed randomised placebo-controlled trials, premenopausal women with HSDD, 24 weeks | Does as-needed subcutaneous bremelanotide improve sexual desire and reduce related distress? | Reported statistically significant improvement in desire (FSFI-D) and reduced distress (FSDS-DAO) versus placebo in both trials. | Women's Health, 2016 |
| Diamond et al., open-label safety extension | Human, open-label extension of the phase 3 programme, up to 52 weeks | What is the longer-term tolerability profile of as-needed bremelanotide? | Nausea, flushing and injection-site reactions were the most common adverse events; transient blood-pressure increases were observed post-dose. | Obstetrics & Gynecology, 2019 |
| Molinoff et al., early male erectile-dysfunction trial | Human, phase 2a, men with erectile dysfunction | Does bremelanotide improve erectile function, and what safety signal ended male-indication development? | Reported improved erectile function alongside a dose-related increase in blood pressure that led to discontinuation of the male development programme. | Annals of the New York Academy of Sciences, 2003 |
Limitations of the PT-141 (Bremelanotide) evidence
- The approved indication is narrow: acquired, generalised HSDD in premenopausal women, as defined by trial entry criteria; efficacy and safety data do not extend to postmenopausal women, men, or other categories of sexual dysfunction on the same evidentiary footing.
- Blood-pressure elevation is a mechanism-based effect (melanocortin receptors influence sympathetic tone), documented across species and study phases, and is the basis for a contraindication in uncontrolled hypertension and cardiovascular disease; repeat, frequent dosing amplifies this concern.
- Nausea is common enough that trial protocols and prescribing guidance recommend antiemetic pretreatment consideration and limit dosing frequency (no more than one dose per 24 hours, and a maximum of 8 doses per month in the approved label).
- Effect sizes on desire and distress scales, while statistically significant, are modest in absolute terms, and the clinical meaningfulness of the specific score changes is debated in the literature.
- Because it also increases MC1R activity, some studies report transient focal hyperpigmentation (e.g. gums, freckles) with repeated dosing, an effect shared with the parent compound melanotan II.
PT-141 (Bremelanotide) laboratory characteristics
Handling and analytical information reported in the literature and in supplier documentation. Values apply to laboratory materials and are not directions for any other use.
| Appearance | White to off-white lyophilised powder |
|---|---|
| Solubility | Water-soluble; a small cyclic heptapeptide |
| Lyophilised storage | Commonly stored at −20 °C, desiccated and protected from light |
| Reconstituted handling | Kept refrigerated and used within the manufacturer-specified window in research protocols |
| Analytical testing | RP-HPLC purity and MS identity are standard checks; the approved product uses pharmaceutical-grade autoinjector formulation with defined stability data |
| Stability considerations | The cyclic disulfide-free lactam structure is relatively stable when kept cold and dry; light exposure and repeated freeze-thaw are the main documented degradation risks |
Frequently asked PT-141 (Bremelanotide) research questions
Is PT-141 the same as melanotan II?
No, but it is closely related. PT-141 (bremelanotide) is a truncated, modified derivative of melanotan II with a different melanocortin receptor activity balance and a distinct clinical development history.
Why did the male erectile-dysfunction programme stop?
A phase 2a trial identified a dose-related increase in blood pressure that was judged unsuitable for the intended repeat-use population, leading the developer to discontinue that indication and pursue female HSDD instead.
What is the approved use of bremelanotide?
It is approved by the FDA as Vyleesi, a subcutaneous injection for acquired, generalised hypoactive sexual desire disorder in premenopausal women, based on the RECONNECT phase 3 trials.
Why is nausea common with this compound?
Melanocortin receptor agonism, including at MC4R in the central nervous system, is mechanistically linked to nausea, and it was the most frequently reported adverse event across the clinical programme.
PT-141 (Bremelanotide) primary references
- Clayton AH, Althof SE, Kingsberg S, et al. (2016). Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Women's Health. https://doi.org/10.2217/whe-2016-0018
- Kingsberg SA, Clayton AH, Portman D, et al. (2019). Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstetrics & Gynecology. https://doi.org/10.1097/AOG.0000000000003500
- Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences. https://doi.org/10.1196/annals.1288.038
Authorship and revision
Compiled from primary literature and public databases. Every factual statement on this page is traceable to a listed reference. Compiled by Peptide Pilots Scientific Content Team; documentation and compliance review by Peptide Pilots Quality & Compliance review. First published ; last revised . Pages are revised when the cited literature changes materially.
Catalogue reference
Peptide Pilots supplies PT-141 as a laboratory reagent with per-lot RP-HPLC and mass-spectrometry documentation. Quantities, testing, packaging and fulfilment details are on the catalogue page.
Related catalogue products
Laboratory reagents supplied by Peptide Pilots from the Reproductive & Sexual-Health Research tier. Research use only; not for human or veterinary use.
