PT-141 (Bremelanotide) – Cyclic Heptapeptide Melanocortin Agonist

Chemical Identity

Chemical Name: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
Synonyms: Bremelanotide; Vyleesi
Molecular Formula: C₅₀H₆₈N₁₄O₁₀
Molecular Weight: 1025.2 Da
CAS Number: 189691-06-3
Structure Type: Cyclic heptapeptide lactam analog of α-MSH

Pharmacological Classification

PT-141 is a **melanocortin receptor agonist** with high affinity for MC₃R and MC₄R, developed for the treatment of **hypoactive sexual desire disorder (HSDD)** in premenopausal women. Unlike phosphodiesterase type 5 inhibitors, PT-141 acts centrally to modulate sexual desire and arousal via melanocortin pathways.

Mechanism of Action

• MC₄R Activation: Stimulates melanocortin-4 receptors in the hypothalamus, enhancing sexual desire and arousal.
• Neurotransmitter Modulation: Influences dopamine and other neurotransmitter pathways involved in sexual behavior.
• Central Nervous System Effects: Acts centrally without significant peripheral vasodilation, differentiating it from traditional ED treatments.

β-Arrestin Recruitment

PT-141's activity at melanocortin receptors involves **G protein-coupled receptor (GPCR)** signaling. While specific data on β-arrestin recruitment is limited, its central mechanism suggests a role for β-arrestin pathways in receptor desensitization and internalization.

Melanocortin Receptor Affinity Profile

Receptor	Affinity	Physiological Role
MC1R	Low	Pigmentation
MC3R	Moderate	Energy homeostasis
MC4R	High	Sexual behavior, appetite
MC5R	Low	Exocrine function

Pharmacokinetics

• Administration: Subcutaneous injection
• Bioavailability: ~100%
• Time to Peak Concentration (T_max): ~1 hour
• Half-Life: ~2.7 hours
• Metabolism: Hydrolysis of peptide bonds
• Excretion: 64.8% urine, 22.8% feces

Biological Effects

Clinical trials have demonstrated that PT-141 significantly improves sexual desire and reduces distress in premenopausal women with HSDD. Its central mechanism offers an alternative to peripheral vasodilators, with potential applications in treating sexual dysfunction in both women and men.

Stability and Storage

• Form: Lyophilized powder
• Solubility: Water, saline
• Storage: –20°C; protect from light and moisture
• Reconstitution: Use sterile water; avoid repeated freeze-thaw cycles

References

1. Simon JA, Kingsberg SA, Portman DJ, et al. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol. 2019;134(5):899-908.
2. Palatin Technologies. Bremelanotide (PT-141) Investigator Brochure. 2019.
3. DrugBank Online. Bremelanotide. https://go.drugbank.com/drugs/DB11653
4. PubChem. Bremelanotide. https://pubchem.ncbi.nlm.nih.gov/compound/9941379