PT-141 10mg

PT-141 (Bremelanotide) — Melanocortin Peptide for Neuroendocrine and Sexual Function Research

Chemical and Biochemical Characteristics

• Full Chemical Name: Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH · nAcOH (n = 1–2)

• Molecular Formula: C₅₀H₆₈N₁₄O₁₀

• Molecular Weight: 1025.18 g/mol

• CAS Number: 189691-06-3

• PubChem CID: 9941379

• Peptide Class: Synthetic cyclic α-melanocyte-stimulating hormone (α-MSH) analogue

• Structure Type: Heptapeptide containing D-phenylalanine; cyclic conformation enhances stability and receptor selectivity

• Primary Targets: Melanocortin-1 receptor (MC1R) and melanocortin-4 receptor (MC4R)

• Developers: Palatin Technologies / AMAG Pharmaceuticals (USA)

• FDA Approval: 2019 – approved under the brand name Vyleesi® for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD)

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Overview

PT-141, also known as Bremelanotide, is a synthetic melanocortin receptor agonist derived from the α-MSH analogue Melanotan II (MT-2).
Unlike vasodilator drugs such as sildenafil (Viagra), PT-141 acts centrally, directly modulating regions of the brain associated with sexual arousal and motivation rather than altering peripheral blood flow.

Originally developed to study melanocortin signaling, PT-141 has since become the first and only FDA-approved medication for female sexual arousal disorder.
Its dual receptor profile (MC4R and MC1R) has also led to exploratory research in neuroprotection, bleeding control, infection response, and oncology.

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Mechanism of Action

PT-141 primarily binds to MC4R, a G-protein-coupled receptor located in the hypothalamus, spinal cord, and limbic system, regions critical to sexual motivation and behavior.
Activation of MC4R increases dopaminergic and sympathetic signaling, producing measurable increases in sexual arousal in both sexes.

It also interacts with MC1R, which is linked to skin pigmentation and tissue repair.
This dual receptor affinity contributes to PT-141’s broader pharmacological profile beyond sexual function.

Key mechanisms include:

• Central neuroendocrine activation of sexual desire and arousal;

• Enhanced dopaminergic tone in hypothalamic nuclei;

• Increased sympathetic drive facilitating genital response;

• MC1R-mediated tissue protection and anti-inflammatory modulation.

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PT-141 and Sexual Function Research

Studies in animal and human models show that MC4R activation by PT-141 enhances sexual motivation, receptivity, and mating behavior in both males and females【1】【2】【3】【4】.

Clinical trials demonstrated:

• In men with erectile dysfunction (ED) unresponsive to sildenafil, nasal administration of PT-141 restored sufficient erectile function for intercourse in roughly one-third of participants【5】.

• In premenopausal women with HSDD, PT-141 significantly increased the number of satisfying sexual events per month and reduced sexual distress scores without major adverse effects【6】.

These findings confirm PT-141’s central mechanism of action — independent of vascular response — and its value for studying the neurobiological regulation of libido.

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Clinical Development and Regulatory History

Despite early promise, PT-141’s path to approval was complex.
Initial trials were paused due to inconsistent endpoints and evolving definitions of female sexual dysfunction (FSD).
Following renewed advocacy from sexual-medicine experts, the Phase II “Reconnect” studies (2017–2018) used subcutaneous administration and improved endpoint criteria.
This led to FDA approval in 2019 for Vyleesi®, now available as a single-use autoinjector for on-demand therapy.

A next-generation formulation, Rekynda™, is currently in late-stage development for broader indications, including both female and male sexual disorders【8】.

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Other Research Areas

Hemorrhagic Shock and Ischemia

In 2009, modified PT-141 analogues were investigated for hemorrhagic and ischemic protection due to MC1R- and MC4R-mediated vasomodulatory effects.
Experimental models showed improved tissue oxygenation and reduced ischemic injury under low-volume conditions.
The optimized derivative, PL-6983, reached Phase IIb clinical evaluation for this indication.

Antifungal and Anti-Inflammatory Properties

PT-141 analogues demonstrated anti-fungal and macrophage-modulating effects via MC1R activation.
In rodent models of Candida albicans vaginitis, treatment induced M2 macrophage polarization and reduced inflammatory burden【9】.
This highlights the potential of melanocortin peptides as broad-spectrum immunomodulators.

Cancer Research

MC1R plays a role in DNA repair and photoprotection, and variants of this receptor are associated with higher risk of basal and squamous cell carcinomas【10】【11】.
Modified PT-141 analogues are being studied for their potential to enhance DNA repair pathways and protect against UV-induced oncogenesis in high-risk populations.

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Emerging Research Directions

PT-141’s pharmacology extends beyond sexual medicine.
Because MC4R is implicated in early-onset obesity, representing up to 6 % of monogenic cases, researchers are exploring PT-141’s impact on energy homeostasis and appetite regulation.
Meanwhile, MC1R involvement in pain signaling, renal physiology, and infection control offers multiple translational pathways for peptide-based interventions.

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Summary

PT-141 (Bremelanotide) is a cyclic melanocortin peptide with wide-ranging applications in research on:

• Central sexual arousal mechanisms;

• Melanocortin receptor pharmacology;

• Neuroendocrine regulation of desire and reward;

• Ischemic and inflammatory protection;

• DNA repair and melanoma-related pathways.

By acting centrally on MC4R rather than peripherally, PT-141 provides a powerful model for exploring neurochemical and hormonal integration of sexual function and melanocortin system physiology.

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Selected References

1. Sandrock M. et al. Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice. Reprod Biol Endocrinol, 2009; 7:24.

2. Rosen R.C. et al. Evaluation of safety and pharmacodynamics of PT-141 in men with inadequate Viagra response. Int J Impot Res, 2004; 16(2): 135–142. [PubMed]

3. Wessells H. et al. Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ induces penile erection via brain and spinal melanocortin receptors. Neuroscience, 2003; 118(3): 755–762. [PubMed]

4. Rössler A.-S. et al. Melanotan II enhances proceptive sexual behaviors in female rats. Pharmacol Biochem Behav, 2006; 85(3): 514–521. [PubMed]

5. Safarinejad M.R., Hosseini S.Y. Salvage of sildenafil failures with Bremelanotide. J Urol, 2008; 179(3): 1066–1071. [PubMed]

6. Clayton A.H. et al. Bremelanotide for female sexual dysfunction: a placebo-controlled dose-finding trial. Womens Health (Lond), 2016; 12(3): 325–337. [PubMed]

7. Miller M.K. et al. Expert opinion on emerging drugs to treat female sexual dysfunction. Expert Opin Emerg Drugs, 2018; 23(3): 223–230. [PubMed]

8. AMAG Pharmaceuticals / Palatin Technologies. Exclusive licensing agreement for Rekynda™ (Bremelanotide). MarketWatch, 2017.

9. Ji H. et al. Synthetic melanocortin (CKPV)₂ exerts antifungal and anti-inflammatory effects via macrophage M2 polarization. PLoS ONE, 2013; 8(2). [PLOS ONE]

10. Maresca V. et al. Skin phototype: a new perspective. Pigment Cell Melanoma Res, 2015; 28(4): 378–389. [PubMed]

11. Feller L. et al. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face. Head Face Med, 2016; 12:11. [PubMed]

12. Spana C. et al. Effect of Bremelanotide on body weight of obese women: data from two phase-1 trials. Diabetes Obes Metab, 2022; 24(6): 1084–1093. [PubMed]

 

 

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