OVERVIEW

PT-141, also known as Bremelanotide, is a synthetic derivative of alpha-melanocyte-stimulating hormone (α-MSH). Initially developed to treat sexual dysfunction in both men and women, it has also been explored for its immune-modulating properties and potential applications in hemorrhagic shock treatment.

PT-141 functions as a melanocortin receptor (MC) agonist, primarily targeting MC-4R and MC-1R, which play roles in sexual arousal, immune function, and vascular regulation. Research suggests that PT-141 can:

• Enhance libido and sexual arousal.
• Improve erectile function in men and increase sexual desire in women.
• Stimulate immune system activity.
• Reduce inflammation and ischemic damage.

Unlike traditional PDE5 inhibitors (e.g., Viagra, Cialis), which work by increasing blood flow, PT-141 acts directly on the central nervous system, making it a potential alternative for individuals with psychogenic sexual dysfunction.

RESEARCH

PT-141 and Sexual Arousal

PT-141’s impact on sexual function is linked to its activation of the MC-4R receptor, found in the central nervous system and associated with sexual behavior and arousal.

• Animal studies showed that MC-4R activation increased mating behavior in both male and female subjects.
• Clinical trials in men with erectile dysfunction (ED)—including those unresponsive to sildenafil (Viagra)—revealed that one-third of participants achieved sufficient erections with PT-141.
• Pre-menopausal women with hypoactive sexual desire disorder (HSDD) experienced:
  • Increased frequency of satisfying sexual events.
  • Reduced distress related to low sexual desire.

Because PT-141 acts via the brain and not the vascular system, it may be particularly effective for non-vascular causes of sexual dysfunction.

PT-141 and Hemorrhagic Shock

In 2009, PT-141 was investigated for acute hemorrhage treatment, with research suggesting potential emergency medicine applications.

• The MC-1R receptor plays a key role in vascular response and blood flow regulation.
• Studies indicated that PT-141 enhanced vascular integrity and reduced ischemic damage in hemorrhagic shock models.

These findings suggest PT-141 or its derivatives could be explored for trauma and critical care medicine.

PT-141 and Immune System Modulation

PT-141 also targets the MC-1R receptor, which is involved in immune regulation.

• Animal studies suggest PT-141 may exhibit:
  • Anti-inflammatory properties.
  • Antimicrobial effects, potentially aiding in infection control.
• MC-1R activation has been linked to immune system support in autoimmune conditions and inflammatory diseases.

This research highlights PT-141’s potential beyond sexual health, particularly in immune and inflammatory disorders.

PT-141 and Cancer Research

Recent studies suggest that PT-141 may influence DNA repair mechanisms:

• The MC-1R receptor is involved in DNA damage repair pathways.
• Individuals with MC-1R mutations have a higher risk of melanoma and skin cancer.

Ongoing research aims to determine whether PT-141 could help prevent certain cancers or support DNA repair in high-risk individuals.

STRUCTURE

• Molecular Formula: C₅₀H₆₈N₁₄O₁₀
• Molecular Weight: 1025.182 g/mol
• Amino Acid Sequence: Ac-Nle-Asp(1)-His-D-Phe-Arg-Trp-Lys(1)
• CAS Registry Number: 189691-06-3
• PubChem Identifier: 9941379

CITATIONS

1. Rosen, R. C. et al. Evaluation of the safety, pharmacokinetics, and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. International Journal of Impotence Research (2004).
2. Wessells, H. et al. PT-141 induces penile erection via brain and spinal melanocortin receptors. Neuroscience (2003).
3. Rössler, A.-S. et al. The melanocortin agonist, Melanotan II, enhances proceptive sexual behaviors in female rats. Pharmacology, Biochemistry, and Behavior (2006).
4. Safarinejad, M. R. & Hosseini, S. Y. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo-controlled study. Journal of Urology (2008).
5. Clayton, A. H. et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Women’s Health (London, England) (2016).
6. Ji, H. et al. The Synthetic Melanocortin (CKPV)2 Exerts Anti-Fungal and Anti-Inflammatory Effects against Candida albicans Vaginitis via Inducing Macrophage M2 Polarization. PLoS ONE (2013).
7. Maresca, V. et al. Skin phototype: a new perspective. Pigment Cell & Melanoma Research (2015).
8. Feller, L. et al. Basal cell carcinoma, squamous cell carcinoma, and melanoma of the head and face. Head & Face Medicine (2016).
9. McMillan, T. R. et al. Melanotan II, a melanocortin agonist, partially rescues the impaired thermogenic capacity of pituitary adenylate cyclase-activating polypeptide deficient mice. Experimental Physiology (2021).
10. Spana, C. et al. Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials. Diabetes, Obesity, and Metabolism (2022).