Table 1. hM₄ Potency, Selectivity, CYP Inhibition, and P-gp Efflux for 8a–i.

^aCalcium mobilization assays with hM₄. IC₅₀ values for hM₄ represent means from at least three (n = 3) independent experiments performed in triplicate.

^bCalcium mobilization assays with hM₂/G_qi5-CHO cells performed in the presence of an EC₈₀ fixed concentration of acetylcholine. IC₅₀ values for hM₂ represent one or two independent experiments performed in triplicate.

^cCytochrome P₄₅₀ cocktail inhibition assay in human liver microsomes (see the SI for further details).

^dBBB penetration potential using Madin Darby canine kidney cells with overexpression of MDR1 gene (encoding for P-gp) in cell monolayers; efflux ratio (ER) is defined as P_app(B-to-A)/P_app(A-to-B) (see the SI for further details).

^eLilly Laboratories cell porcine kidney 1-MDR1 cell line was used for comparison.

^fCalculated using ChemDraw Professional version 20.1.