PCS1055 dihydrochloride is an effective, selective, and competitive muscarinic M4 receptor antagonist (IC50: 18.1 nM and a Kd: 5.72 nM). PCS1055 dihydrochloride is also a potent AChE inhibitor (IC50 s: 22 nM and 120 nM for electric eel and human AChE, respectively). PCS1055 dihydrochloride inhibits radioligand [3H]-NMS binding to the M4 receptor (Ki: 6.5 nM). PCS1055 dihydrochloride shows >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor.

M4 mAChR:（kd）5.72 nM, M4 mAChR:18.1 nM

PCS1055 effectively inhibits G protein activation in a concentration-dependent manner, demonstrating its highest potency at M4 receptors. Research indicates that PCS1055 shows a pronounced binding and functional preference for the M4 receptor subtype, surpassing its affinity and effectiveness for M1-, M2-, M3-, and M5 receptors by 130-, 31.2-, 426-, and >1000-fold, and 255-, 69.1-, 342-, and >1000-fold, respectively. Furthermore, PCS1055 counteracts functional signal transduction, evidenced by its ability to inhibit agonist-stimulated GTP-γ-[35S] binding, showcasing its antagonistic properties.

PCS1055 (30 mg/kg; intraperitoneal injection; male mice) treatment achieves peak plasma levels at 30 minutes, with total and unbound plasma concentrations of 45100 nM and 631 nM, respectively. At 1 hour, maximal brain exposure of the compound is observed at 11.8 nM [1].