| Description |
PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC50 of 18.1 nM and a Kd of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [3H]-NMS binding to the M4 receptor with a Ki 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].
|
| Related Catalog |
|
| 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]. Animal Model: Male mice[1] Dosage: 30 mg/kg Administration: Intraperitoneal injection (Pharmacokinetic Analysis) Result: The maximal plasma levels were observed at the 30 min time-point with 45100 nM total and 631nM unbound plasma concentrations. The maximal compound exposure observed in the brain was 11.8 nM at 1 h.
|
| References |
[1]. Croy CH, et al. Characterization of PCS1055, a novel muscarinic M4 receptor antagonist. Eur J Pharmacol. 2016 Jul 5;782:70-6. [2]. Contreras JM, et al. Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. J Med Chem. 2001 Aug 16;44(17):2707-18.
|
