TABLE 2

Inhibition binding parameters for WIN 62,577 against [3H]QNB in combination with a range of orthosteric ligands at M4 mAChRs in CHO cell membranes

Parameters derived from nonlinear regression analysis are presented as the mean ± S.E.M. (n = 5). LogKA is the logarithm of each ligand's equilibrium dissociation constant based on the extended TCM reaction scheme shown in Fig. 2. LogKB is the logarithm of the cooperativity factor for the interaction between WIN 62,577 and [3H]QNB. Antilogarithm (geometric mean) is shown in parentheses. LogKI is the logarithm of the cooperativity factor for the interaction between WIN 62,577 and the indicated unlabeled orthosteric ligand. Antilogarithm (geometric mean) is shown in parentheses.

Ligand LogKA LogKB LogKI Logα Logβ
QNB −10.2 ± 0.05 −0.60 ± 0.01 (0.25)
Atropine −8.73 ± 0.04 −0.27 ± 0.01 (0.54)
ACh −5.32 ± 0.02 −0.92 ± 0.01 (0.12)
McN-A-343 −5.29 ± 0.02 −0.30 ± 0.03 (0.50)
Xanomeline −7.50 ± 0.04 −0.27 ± 0.01 (0.54)
WIN 62,577 −5.47 ± 0.04