For research use only. Not for therapeutic Use.
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].
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].
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].
| Catalog Number | I011979 |
| CAS Number | 361979-40-0 |
| Synonyms | N-[2-(1-benzylpiperidin-4-yl)ethyl]-3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-amine;dihydrochloride |
| Molecular Formula | C27H34Cl2N4 |
| Purity | ≥95% |
| InChI | InChI=1S/C27H32N4.2ClH/c1-2-7-22(8-3-1)20-31-17-14-21(15-18-31)13-16-28-26-19-24-11-6-10-23-9-4-5-12-25(23)27(24)30-29-26;;/h1-5,7-9,12,19,21H,6,10-11,13-18,20H2,(H,28,29);2*1H |
| InChIKey | VSCSFYDNGYAWKG-UHFFFAOYSA-N |
| SMILES | C1CC2=CC=CC=C2C3=NN=C(C=C3C1)NCCC4CCN(CC4)CC5=CC=CC=C5.Cl.Cl |
| Reference | [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. |
