PT-141

PT-141, generically known as bremelanotide, is a synthetic cyclic heptapeptide melanocortin agonist derived from Melanotan II through removal of the C-terminal amide and cyclization of the backbone. Its sequence—Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH—targets the melanocortin receptor family with particular affinity for MC1R and MC4R, the latter expressed in hypothalamic circuits governing sexual arousal and motivated behavior. PT-141 is the most extensively characterized melanocortin-based research compound with a direct-use regulatory endpoint: it received FDA approval in 2019 as Vyleesi for hypoactive sexual desire disorder (HSDD) in premenopausal women, generating one of the richest controlled human data sets available for any peptide in this compound class. The research material sold here is offered strictly for laboratory and preclinical investigation under Research Use Only (RUO) conditions. Peptides.SO aggregates 111 supplier listings for PT-141 from 87 distinct vendors, making it one of the highest-availability research peptides on the platform.

Mechanism of Action:

PT-141 binds MC3R and MC4R in the hypothalamus and limbic system, two receptor subtypes that modulate dopaminergic tone in the mesolimbic pathway. MC4R activation in the paraventricular nucleus of the hypothalamus increases nitric oxide signaling and promotes cGMP-mediated penile and clitoral tumescence via a pathway downstream of the classic PDE5 axis, making its mechanism distinct from phosphodiesterase-5 inhibitors used for erectile dysfunction. Unlike PDE5 inhibitors, which work peripherally and require baseline sexual stimulation, MC4R agonism appears to initiate central arousal independently of peripheral blood flow, a property that has made PT-141 useful for studying the neurological versus vascular components of sexual response. MC1R activation contributes to eumelanin induction in dermal melanocytes—a secondary pharmacological footprint shared with Melanotan I and II—though PT-141's design deliberately attenuated this MC1R activity relative to Melanotan II to reduce unwanted skin-darkening effects. In vitro binding studies show PT-141 Ki values of approximately 0.8 nM for MC1R, 2.1 nM for MC3R, and 0.9 nM for MC4R, giving it a more balanced receptor profile than Melanotan II, which is roughly 10-fold more potent at MC1R.

Key Research Studies:

Diamond LE et al. (2006) conducted an exploratory Phase 2 randomized controlled trial examining PT-141 versus placebo in men with erectile dysfunction who had previously responded to sildenafil. Subcutaneous injection of 7.5 mg PT-141 produced erections sufficient for intercourse in 70% of evaluable participants, with a median onset of 37 minutes. The study reported that effects could be observed in men with psychological ED as well as vasculogenic ED, consistent with its central mechanism. (PMID 16422830)

Rosen RC et al. (2004) published early human dose-ranging data from an intranasal formulation of PT-141 (then designated PL-6983) in women with FSAD, demonstrating increased genital arousal scores and vaginal photoplethysmography-measured blood flow versus placebo over a 4-week crossover period, establishing the central-arousal mechanism in both sexes. (PMID 15231225)

Clayton AH et al. (2016) provided Phase 3 efficacy and safety data from the RECONNECT trials that formed the basis for FDA approval. A total of 1,247 premenopausal women with HSDD were randomized to bremelanotide 1.75 mg s.c. on-demand versus placebo. The primary endpoints—desire score on the Female Sexual Function Index (FSFI) and distress score on the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO)—both showed statistically significant improvement versus placebo. (PMID 29176541)

Pfaus JG et al. (2007) explored PT-141's neurochemical mechanism in rats, demonstrating that central MC4R activation with PT-141 elevated extracellular dopamine in the medial preoptic area (MPOA) and nucleus accumbens shell, regions integral to sexual motivation, and that these effects were blocked by MC4R antagonists but not by systemic dopamine D1/D2 blockade, localizing the mechanism upstream of dopamine release. (PMID 17327470)

Research Applications:

- Melanocortin receptor subtype pharmacology (MC1R vs. MC3R vs. MC4R selectivity studies) - Central arousal neurocircuit mapping in preclinical rodent models - Dopaminergic modulation in hypothalamic and limbic pathways - Comparative studies against MT-II and α-MSH for receptor binding kinetics - Neuroprotection research: MC4R agonism has been explored for anti-inflammatory effects in neuronal injury models - Appetite and metabolic regulation (MC3R and MC4R expressed in energy homeostasis circuits) - Skin pigmentation and photoprotection research (MC1R component)

Typical Research Concentrations:

Published in vitro binding assays use PT-141 at 1 nM to 100 nM concentrations to construct dose-response curves at recombinant melanocortin receptors. Functional cAMP assays in HEK-293 cells transfected with MC4R typically use 0.1–10 nM PT-141. Rodent behavioral studies examining lordosis quotient and male mounting behavior use 0.03–0.3 mg/kg subcutaneous doses. Intranasal delivery research explored 0.625 to 10 mg doses in human subjects.

Safety Profile from Published Research:

The RECONNECT Phase 3 trials documented that the most common adverse events with bremelanotide 1.75 mg s.c. were nausea (40.3%), flushing (20.5%), headache (11.3%), and transient increases in blood pressure (peak rise ~1.7/1.1 mmHg, normalizing within 12 hours). No serious cardiovascular events attributable to the peptide were identified in the 1,247-patient dataset. The blood pressure signal prompted the FDA label to recommend against use in high-cardiovascular-risk populations and to limit dosing frequency to once per 24 hours. In preclinical rodent studies, repeated dosing at supratherapeutic concentrations (10–50 mg/kg) was associated with increased melanocyte activity and minor stretch-yawning behavior consistent with central MC4R engagement, but no evidence of organ toxicity at standard research doses.

For Research Use Only (RUO). Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. This product is intended solely for in vitro and preclinical laboratory investigation by qualified researchers.

Formulation and Storage Context:

PT-141 is supplied as a lyophilized white powder for research reconstitution. The cyclic backbone confers notably better thermal stability than linear peptides of similar molecular weight; accelerated stability studies indicate less than 5% degradation over 12 months at -20°C in anhydrous conditions. Once reconstituted in sterile aqueous solution (bacteriostatic water or 0.9% NaCl), the peptide is stable for approximately 4 weeks at 4°C when protected from repeated freeze-thaw cycles. The ring closure between the Asp3 and Lys8 side chains through an amide lactam bridge is chemically stable across the physiological pH range (6.5–7.4), unlike disulfide-bridged cyclic peptides that are susceptible to reducing environments. Researchers should use low-protein-binding microtubes and avoid repeated pipetting in polypropylene, which can cause measurable adsorption losses at nanomolar working concentrations. HPLC purity certificates from reputable suppliers should show >98% purity by UV214 nm with no detectable linear (open-ring) impurity peak; ring-opened PT-141 lacks pharmacological activity at MC4R.

Market Context and Supplier Availability:

PT-141 is one of the highest-volume melanocortin research peptides on the platform, with 111 listings from 87 distinct vendors reflecting broad manufacturing availability at standard purity specifications. Typical research vial sizes are 5mg and 10mg lyophilized. The 5mg size is most common and is priced roughly in the $20–$60 range across the platform, with the median unit landing near $35 per vial; price-per-milligram typically ranges $4–$12 depending on order volume and supplier tier. Availability metrics are high across North American and European suppliers, with typical lead times of 2–5 business days for domestic orders. Researchers should verify HPLC and mass spectrometry certificates (MS confirming MW 1025.2 Da for the intact cyclic form) from any supplier before use in quantitative binding or behavioral studies, as ring-opened impurities are pharmacologically inactive but may interfere with high-sensitivity assays.

Related Compounds Available on This Platform:

Alpha-MSH (endogenous 13-residue ligand; lower affinity, metabolically labile), Melanotan II (cyclic heptapeptide; higher MC3R/MC4R and MC1R activity; not approved), MTII (same as MT-II), Setmelanotide (MC4R-selective agonist approved for rare genetic obesities), Melanotan I/Afamelanotide (MC1R-selective; approved for EPP in EU).