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PT-141

PT-141 (Bremelanotide): A Melanocortin Receptor Agonist Approved for HSDD

Research summary. PT-141, also known by its INN bremelanotide, is a synthetic cyclic heptapeptide melanocortin receptor agonist derived from the alpha-melanocyte-stimulating hormone (α-MSH) lineage. It binds preferentially to MC4R with additional activity at MC1R. Bremelanotide was approved by the FDA in 2019 under the trade name Vyleesi for the treatment of acquired, generalised hypoactive sexual desire disorder (HSDD) in premenopausal women, making it one of relatively few peptide drugs to reach approval for a sexual-function indication. Earlier development for acute haemorrhage was abandoned.

Molecular profile

  • Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
  • Molecular formula: C₅₀H₆₈N₁₄O₁₀
  • Molecular weight: ~1025.2 g/mol
  • PubChem CID: 9941379
  • CAS number: 189691-06-3
  • Class: Melanocortin receptor agonist (MC4R-preferring)
  • Synonyms: Bremelanotide; Vyleesi (brand); PT-141

Mechanism of action

Unlike phosphodiesterase-5 inhibitors such as sildenafil — which act peripherally on vascular smooth muscle to support genital arousal — bremelanotide acts centrally:

  • MC4R agonism in the central nervous system. MC4R is widely expressed in hypothalamic regions involved in sexual behaviour and food intake. Activation of MC4R is thought to underlie the pro-sexual-desire effects observed in clinical studies.
  • MC1R activity. Off-target activity at MC1R contributes to the characteristic transient skin-darkening and flushing effects observed in some research subjects.
  • Origin from melanotan II. Bremelanotide is structurally related to and was derived from melanotan II, but lacks the C-terminal amide and has a distinct cyclisation, producing a different receptor-activity profile.

The central mechanism contrasts with peripheral vasoactive approaches and is the basis for bremelanotide's regulatory positioning as a treatment for desire-domain (rather than arousal-physiology) dysfunction.

Preclinical and clinical research highlights

Preclinical sexual-behaviour models. Rodent studies have reported MC4R-mediated increases in proceptive sexual behaviours and in penile-erection responses, supporting the central pro-sexual-function hypothesis.

Phase 2 and Phase 3 HSDD trials. Pivotal Phase 3 trials (RECONNECT 301 and RECONNECT 302) evaluated bremelanotide on-demand in premenopausal women with HSDD and reported statistically significant improvements in validated desire and distress endpoints relative to placebo, supporting the 2019 FDA approval of Vyleesi.

Safety profile in clinical research. Reported adverse effects include nausea (most common), flushing, injection-site reactions, headache, and transient blood pressure increases. The drug carries label warnings regarding blood pressure and is contraindicated in uncontrolled hypertension or cardiovascular disease.

Earlier indications. Phase 2 work in acute hypovolaemic shock and in male erectile dysfunction was conducted but did not lead to approval in those indications.

Current research status

Bremelanotide is an FDA-approved drug for acquired, generalised HSDD in premenopausal women (Vyleesi, 2019, AMAG/Palatin). It is administered subcutaneously on-demand prior to anticipated sexual activity. Approval is specifically for premenopausal women, and use outside this population is off-label.

Research peptide supply of "PT-141" is widespread for laboratory use, but the existence of an approved, regulated drug product is a meaningful distinction. Researchers and customers should be aware that the regulated product is the appropriate channel for therapeutic use, while research-grade material is for in-vitro and animal-model work only.

Key takeaways for researchers

  • PT-141 / bremelanotide is a cyclic heptapeptide melanocortin receptor agonist (MC4R-preferring) derived from the α-MSH lineage.
  • It is FDA-approved as Vyleesi (2019) for acquired, generalised HSDD in premenopausal women, administered subcutaneously on-demand.
  • The mechanism is central MC4R agonism, distinct from peripheral PDE-5 inhibitor approaches.
  • Common reported effects include nausea, flushing, and transient blood-pressure increases.
  • Research-grade PT-141 is for laboratory use only and is not a substitute for the regulated drug product.

References

  1. Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899–908.
  2. Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med. 2006;3(4):628–638.

This article is provided for educational and research purposes only. PT-141 / bremelanotide research material is supplied for laboratory use and is not intended for human consumption outside of an approved, regulated drug product (Vyleesi). It is not intended for diagnosis, treatment, cure, or prevention of any disease or condition. All work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.

PT-141 | BonesLabs