PT-141 (Bremelanotide) --- Research Product Overview

**Disclaimer:** This article is provided for educational and research purposes only. The research-grade PT-141 sold by Viking Labs is not approved by the FDA for human use and is intended exclusively for in-vitro and laboratory animal research. A pharmaceutical formulation of bremelanotide is FDA-approved as Vyleesi for hypoactive sexual desire disorder in premenopausal women; that approved drug product is distinct from research-grade PT-141 and should not be conflated with it. Nothing in this article constitutes medical advice or a recommendation for self-administration.

Introduction

PT-141, also known as bremelanotide, is a synthetic cyclic heptapeptide melanocortin-receptor agonist derived from melanotan II. Where melanotan II is a non-selective melanocortin agonist whose principal pharmacological effect is pigmentary (via MC1R) and whose sexual-arousal effects in early human studies were essentially incidental to that primary indication, PT-141 was developed to retain the central melanocortin-mediated arousal effects while substantially reducing pigmentary signaling. Its development by Palatin Technologies culminated in FDA approval of the pharmaceutical formulation Vyleesi (bremelanotide injection) on June 21, 2019, for hypoactive sexual desire disorder (HSDD) in premenopausal women. The research-grade material discussed here is chemically identical to the active pharmaceutical ingredient but is supplied as bulk lyophilized peptide for laboratory use only.

For background on the broader receptor family and related peptides, see the melanocortin system and melanotan II and the melanocortin receptors.

Sequence and Physicochemical Properties

Bremelanotide is a cyclic heptapeptide with the primary sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, where the cycle is closed by an amide bond between the Asp side-chain carboxyl and the Lys side-chain epsilon-amine. The N-terminal norleucine is acetylated. The molecular formula is C50H68N14O10 with a monoisotopic mass of approximately 1024.5 Da and an average molecular mass of ~1025.2 Da.

The cyclic backbone confers conformational rigidity that drives both receptor selectivity (favoring MC3R/MC4R over MC1R relative to the parent alpha-MSH) and proteolytic stability. The peptide is moderately water-soluble; solubility can be improved with mild acidification (e.g., 0.5--1 percent acetic acid) prior to dilution into neutral buffer for cell-culture work.

Research-grade material targets HPLC purity of >=98 percent. Mass-spectrometric confirmation should show the parent ion at m/z 1025.5 M+H]+ (or m/z 513.3 [M+2H]2+ in ESI). Investigators should review the Certificate of Analysis for sequence confirmation, purity, residual TFA, water content, and endotoxin levels (typically <1 EU/mg for cell-culture-grade material). The [CoA reading guide walks through each specification.

Mechanism of Action

PT-141 is a non-selective melanocortin-receptor agonist with measurable activity at MC1R, MC3R, MC4R, and MC5R. Its pharmacologically relevant effects in models of sexual function are mediated principally by central MC4R activation in hypothalamic and limbic circuits, particularly the medial preoptic area and the paraventricular nucleus. This contrasts with phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, which act peripherally on penile vascular tone.

Activation of MC4R triggers Gs-coupled adenylyl cyclase activation, elevating cAMP in target neurons and modulating downstream dopaminergic and oxytocinergic signaling implicated in sexual motivation and arousal. PT-141's effects on female sexual function in clinical studies are believed to operate through the same central circuitry rather than through any direct effect on peripheral genital tissue.

Preclinical and Clinical Research Summary

PT-141 has been evaluated extensively in both preclinical and clinical settings. Diamond et al. (2004) reported that intranasal PT-141 produced dose-dependent erectile responses in normal men and patients with mild-to-moderate erectile dysfunction; subsequent oral and subcutaneous formulations confirmed central, MC4R-mediated effects across multiple cohorts. The pivotal trials supporting Vyleesi's approval (NCT02333071 and NCT02338960) enrolled premenopausal women with acquired, generalized HSDD and demonstrated statistically significant improvements in desire and reductions in distress relative to placebo across 24 weeks of as-needed dosing.

Reported adverse events in the clinical program include nausea (the most common, affecting roughly 40 percent of subjects), flushing, injection-site reactions, and transient blood-pressure elevations. The melanocortin mechanism also produces dose-dependent darkening of pigmented skin and gum tissue in a subset of subjects, reflecting residual MC1R activity.

Common Research Applications

PT-141 is used in research to:

• Investigate central MC4R-mediated regulation of sexual motivation in rodent and primate models.
• Probe melanocortin-receptor pharmacology in vitro using transfected receptor cell lines.
• Compare central versus peripheral pharmacology of erectile and arousal pathways.
• Develop pharmacokinetic and formulation studies for cyclic peptide delivery.

Comparator Peptides and Molecules

PT-141 is best understood by direct mechanistic comparison with other compounds active on sexual function and erectile pathways, since each operates through a fundamentally different pharmacological circuit.

PT-141 vs. sildenafil (and other PDE5 inhibitors). Sildenafil, tadalafil, and vardenafil act peripherally by inhibiting phosphodiesterase-5 in penile vascular smooth muscle, prolonging cGMP-mediated nitric-oxide signaling and producing erectile-tissue vasodilation. They require pre-existing sexual stimulus (the NO signal must be generated upstream) and do not engage central arousal circuitry. PT-141 acts centrally on MC4R-expressing neurons in the medial preoptic area and paraventricular nucleus, modulating dopaminergic and oxytocinergic outflow that drives sexual motivation upstream of peripheral vascular events. The two mechanisms are conceptually orthogonal --- one acts on motivation/arousal, the other on penile hemodynamic response --- and represent the cleanest pharmacological dissociation in the field. For broader context on the NO/cGMP axis, see nitric oxide peptides.

PT-141 vs. apomorphine. Apomorphine is a non-selective dopamine receptor agonist (D1/D2) that produces central pro-erectile effects through dopaminergic activation of the medial preoptic area. Apomorphine SL (Uprima) reached late-stage clinical development for erectile dysfunction but was withdrawn from European markets in 2006 due to limited efficacy and a substantial nausea-and-emesis profile mediated by area-postrema D2 activation. PT-141's MC4R-driven mechanism is closer to the dopaminergic circuitry apomorphine engages but operates upstream of the dopaminergic relay --- which is why MC4R activation produces dopamine release in the medial preoptic area in microdialysis studies.

PT-141 vs. melanotan II. The closest direct chemical comparator. Melanotan II is a non-selective melanocortin agonist whose principal pharmacological activity is pigmentary (MC1R-mediated) with sexual-arousal effects emerging incidentally during early human melanin-induction studies. PT-141's structural modifications shifted receptor selectivity toward MC3R/MC4R, retaining the central arousal effects while substantially attenuating the pigmentary signal. The trade-off is incomplete: clinical-trial subjects on PT-141 still show dose-dependent transient hyperpigmentation in a subset, reflecting residual MC1R activity. See the melanotan II overview for the parent compound.

PT-141 vs. flibanserin. Flibanserin (Addyi) is the other FDA-approved drug for HSDD in premenopausal women and acts as a 5-HT1A agonist / 5-HT2A antagonist taken daily orally. Its mechanism is fundamentally different (serotonergic, daily dosing) from bremelanotide's melanocortin-pathway-on-demand subcutaneous injection.

Deeper Preclinical Breakdown

Three studies define the modern PT-141 evidence base.

Pfaus et al. (2007), Journal of Sexual Medicine (PMID 17873892). This preclinical-overview paper synthesized the central CNS effects of bremelanotide on female sexual function. Using a rat model of female sexual behavior, the investigators demonstrated that subcutaneous bremelanotide (50--500 microg/kg) activated c-fos expression in the medial preoptic area and ventromedial hypothalamus --- the canonical female-sexual-motivation circuitry --- and increased solicitation behavior in receptive female rats interacting with sexually experienced males. Microinjection of bremelanotide directly into the medial preoptic area replicated the systemic effect, while microinjection into adjacent structures did not, establishing anatomical specificity. The paper also reviewed parallel male-rat data showing increased non-contact erections and mounting frequency on bremelanotide pretreatment.

Diamond et al. (2004). The first published human data on intranasal PT-141 in normal men and patients with mild-to-moderate erectile dysfunction. Single-dose intranasal bremelanotide (4--20 mg) produced dose-dependent erectile responses measured by RigiScan in a placebo-controlled crossover. This paper established the central mechanism in humans (consistent with ED unresponsive to PDE5 inhibitors showing response to bremelanotide in subsequent studies) and led to the subcutaneous formulation that became Vyleesi.

Kingsberg et al. (2019), Obstetrics and Gynecology (RECONNECT trials, PMID 31599831). The pivotal phase 3 program comprised two identical 24-week randomized double-blind placebo-controlled trials (NCT02333071, NCT02338960) enrolling 1247 premenopausal women with acquired generalized HSDD. Bremelanotide 1.75 mg subcutaneous on-demand produced statistically significant improvements in the Female Sexual Function Index desire domain and reductions in distress on the Female Sexual Distress Scale relative to placebo (p<0.001 integrated). Adverse events: nausea (40 percent), flushing (20 percent), injection-site reactions, headache; transient blood-pressure elevations (<10 mmHg average) led to FDA labeling guidance against use in subjects with uncontrolled hypertension. These trials supported the June 21, 2019 FDA approval of Vyleesi.

Formulation Considerations

Research-grade PT-141 (bremelanotide) is supplied as a lyophilized white-to-off-white powder, typically in 5 mg or 10 mg sealed glass vials under inert atmosphere with desiccant. The cyclic structure provides better lyophilization stability than linear melanocortin peptides; lyophilized vials are stable for >=24 months at -20 degrees C. Recommended diluent for multi-day research use is bacteriostatic water containing 0.9 percent benzyl alcohol; brief mild acidification (0.5--1 percent acetic acid) can improve initial dissolution before subsequent dilution into PBS or saline. The cyclic [Asp-His-D-Phe-Arg-Trp-Lys] backbone is less susceptible to proteolysis than alpha-MSH but is still vulnerable to oxidation of the tryptophan residue under prolonged light exposure --- amber vials and light-protected storage are preferred. Common synthetic impurities include open-chain (uncyclized) precursor and partial-acetylation byproducts visible on RP-HPLC. The FDA-approved Vyleesi pharmaceutical formulation uses a citrate-buffered single-use prefilled autoinjector at pH 4.5--5.5; research-grade material in BAC water at neutral pH is chemically equivalent in receptor-pharmacology terms but differs in formulation.

Research-Context Dosing Ranges

Published preclinical and clinical studies provide research-context dose anchors. In-vitro receptor-binding assays at MC1R/MC3R/MC4R/MC5R-transfected cell lines have used 0.1--100 nM for cAMP-accumulation EC50 determination. Rodent subcutaneous studies have used 50--500 microg/kg for behavioral sexual-motivation readouts and c-fos activation studies. Primate sexual-behavior studies have used 0.05--0.5 mg/kg subcutaneously. The FDA-approved Vyleesi human dose is 1.75 mg subcutaneous on-demand; clinical phase 2 dose-finding (Clayton et al.) tested 0.75, 1.25, and 1.75 mg with the 1.75 mg dose advanced to phase 3. These figures are reported as research-context anchors and the Vyleesi human dose is included only for completeness regarding the FDA-approved equivalent --- research-grade PT-141 sold by Viking Labs is not interchangeable with the Vyleesi pharmaceutical product.

Cross-References

For broader context within the Viking Labs research library, see the melanocortin system overview for the receptor family and signaling architecture, the melanotan II overview for the parent comparator compound, the kisspeptin reproductive overview for an upstream reproductive-axis modulator, and nitric oxide peptides for the parallel peripheral-vasodilation pathway. Handling and analytical protocols are covered in the peptide reconstitution guide and how to read a peptide CoA.

Handling, Reconstitution, and Storage

Lyophilized PT-141 is stable at -20 degrees C for >=24 months in sealed vials with desiccant. Reconstitution is standard for cyclic peptides: bacteriostatic water (0.9 percent benzyl alcohol) or sterile water for animal research, sterile saline or PBS for cell culture, with brief mild acidification if dissolution is incomplete. Stock solutions of 1--10 mg/mL are typical. Reconstituted material should be aliquoted to minimize freeze--thaw cycles; refrigerated working dilutions are typically stable for 14--28 days when reconstituted in bacteriostatic water. The cyclic structure provides better solution stability than linear melanocortin peptides such as alpha-MSH itself.

Summary

PT-141 (bremelanotide) is a cyclic heptapeptide melanocortin agonist whose pharmacological profile and FDA-approved pharmaceutical equivalent (Vyleesi) place it among the most extensively studied research peptides in the melanocortin family. Its central, MC4R-mediated mechanism of action distinguishes it both from peripheral PDE5 inhibitors and from melanocortin agonists with stronger MC1R-mediated pigmentary effects. Research-grade material from Viking Labs is intended for in-vitro and laboratory animal research only and should not be confused with the FDA-approved Vyleesi pharmaceutical product.

*This article is provided for informational and research purposes only. Viking Labs does not sell products intended for human consumption.*