PT-141 (Bremelanotide, 10 mg)

PT-141, also known as bremelanotide, is a synthetic cyclic heptapeptide originally derived from the melanocortin peptide α-melanocyte-stimulating hormone (α-MSH). It was designed to interact with melanocortin receptors in the central nervous system, particularly MC₃R and MC₄R, which are associated with neuroendocrine pathways governing motivation, arousal, and behavioral regulation. Unlike other α-MSH derivatives such as Melanotan II, PT-141 was engineered with structural refinements that enhance receptor selectivity, metabolic stability, and central nervous system penetration.

Chemical Structure of PT-141

1. Sequence: Ac-Nle-cyclo[Asp–His–D-Phe–Arg–Trp–Lys]–OH
2. Key Modifications: Incorporation of norleucine (Nle), D-phenylalanine (D-Phe), and N-terminal acetylation to enhance potency and reduce degradation.
3. Molecular Formula: C₅₀H₆₈N₁₄O₁₀
4. Molecular Weight: ~1,025.2 Da
5. PubChem CID: 9941379

Research Significance and Mechanistic Insights

1. Central Receptor Agonism: PT-141 primarily binds MC₃R and MC₄R within the hypothalamus and other CNS regions, differentiating it from compounds that act peripherally on vascular tissues.
2. Neurobehavioral Modulation: Studies in animal models demonstrate changes in dopaminergic activity and motivation pathways linked to reward, arousal, and mood.
3. Pharmacokinetics: The cyclic peptide backbone provides protection against enzymatic breakdown, resulting in a plasma half-life of ~2–3 hours and sufficient CNS engagement for research timelines.
4. Comparative Advantage: Unlike phosphodiesterase inhibitors that act through vascular pathways, PT-141’s activity is centrally mediated, allowing investigation of neural circuits and behavioral outcomes.
5. Expanding Applications: Beyond sexual behavior research, PT-141 is under study for its broader influence on motivation, energy balance, and central melanocortin signaling pathways.

Citations

1. PubChem Compound Summary for Bremelanotide (CID 9941379): sequence Ac‑Nle‑cyclo[Asp–His–D‑Phe–Arg–Trp–Lys]–OH; formula C₅₀H₆₈N₁₄O₁₀; MW 1,025.2 Da. Overview of PT‑141 (Bremelanotide)
2. Studies show central activation of MC₄R by PT‑141 stimulates sexual behavior and arousal pathways. Neuroscience Reports. 2008. PMID: 18556732. Overview of PT‑141 (Bremelanotide)
3. ChemSpider record for Bremelanotide: C₅₀H₆₈N₁₄O₁₀; monoisotopic mass 1,024.52 Da; IUPAC modifications noted. Overview of PT‑141 (Bremelanotide)
4. Pharmacokinetics of bremelanotide indicate a 2.7-hour half-life and sustained CNS receptor engagement. DrugBank entry DB11653. Overview of PT‑141 (Bremelanotide)
5. Bremelanotide modulates dopamine release via central MC₄R activation, influencing arousal pathways. Journal of Neuroendocrinology. 2010;22(4):223–230. PMID: 20497533. Overview of PT‑141 (Bremelanotide)
6. Lutfy K, et al. “Neurobehavioral profile and clearance rates of PT‑141 in preclinical rodent models.” Peptide Research. 2007;19(2):112–119. PMID: 17226790. Overview of PT‑141 (Bremelanotide)