PT-141

Overview

PT-141 (bremelanotide) is a cyclic heptapeptide melanocortin receptor agonist derived from Melanotan II through removal of the C-terminal amide. It acts primarily on MC3R and MC4R receptors in the central nervous system. Unlike its parent compound MT2, PT-141 has minimal effects on melanogenesis via MC1R, making it a more selective tool for studying central melanocortin pathways. Under the brand name Vyleesi, bremelanotide received FDA approval in 2019, representing one of the few peptide drugs targeting CNS melanocortin receptors to reach clinical use.

Mechanism of Action

PT-141 activates MC3R and MC4R in the hypothalamus and limbic system. MC4R activation in the paraventricular nucleus triggers downstream signalling through oxytocin and dopaminergic pathways, while MC3R modulation in the ventral tegmental area influences reward circuitry. The compound acts through Gs-coupled cAMP elevation and Gq-coupled calcium signalling, depending on the receptor subtype and cellular context. Its central mechanism of action, distinct from peripheral vasodilatory pathways, makes it a unique pharmacological tool for studying the intersection of melanocortin signalling and behavioural neuroscience.

Research Applications

• Central melanocortin receptor (MC3R/MC4R) research
• Hypothalamic neuropeptide pathway investigation
• Oxytocin and dopaminergic circuit interaction studies
• Behavioural neuroscience and reward pathway research
• Melanocortin structure-activity relationship studies