PCS1055 (dihydrochloride)

PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC₅₀ of 18.1 nM and a K_d of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [³H]-NMS binding to the M4 receptor with a K_i of 6.5 nM. PCS1055 dihydrochloride exhibits >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor. PCS1055 dihydrochloride is also a potent AChE inhibitor with IC₅₀ s of 22 nM and 120 nM for electric eel and human AChE, respectively^[1][2]. IC50 & Target: IC50: 18.1 nM (Muscarinic M4 receptor); Kd: 5.72 nM (Muscarinic M4 receptor)^[1];
IC50: 22 nM (Electric eel AChE) and 120 nM (Human AChE)^[2] In Vitro: PCS1055 also antagonized functional signal transduction as demonstrates by the inhibition of agonist-stimulated GTP-γ-[³⁵S] binding. PCS1055 inhibits G protein activation in a concentration dependent manner, with the highest potency at the M4 receptors. Both studies shows that PCS1055 is most potent at the M4 receptor subtype with a binding preference of 130-, 31.2-, 426- and >1000-fold, and functional preference of 255-, 69.1-, 342- and >1000-fold over the M1-, M2-, M3- and M5 receptors, respectively^[1]. In Vivo: PCS1055 (30 mg/kg; intraperitoneal injection; male mice) treatment shows the maximal plasma levels at the 30 min time-point with 45100 nM total and 631nM unbound plasma concentrations. The maximal compound exposure observed in the brain is 11.8 nM at 1 h^[1].