TABLE 1

Inhibition binding parameters for benzimidazole allosteric modulators using [3H]NMS or [3H]QNB at M1 or M4 mAChRs in CHO cell membranes

Parameters derived from nonlinear regression analysis are presented as the mean ± S.E.M. (n = 3-4). LogKB is the logarithm of the modulator equilibrium dissociation constant. Logα is the logarithm of the cooperativity factor. Antilogarithm (geometric mean) is shown in parentheses.

Ligand M1 mAChR M4 mAChR
LogKB Logα LogKB Logα
[3H]NMS
WIN 51,708 −6.01 ± 0.12 −0.23 ± 0.01* (0.59) −6.34 ± 0.21* 0.68 ± 0.15* (4.77)
WIN 62,577 −5.38 ± 0.35 −0.75 ± 0.05* (0.18) −5.41 ± 0.31* −0.14 ± 0.04* (0.73)
[3H]QNB
WIN 51,708 −5.98 ± 0.04* −0.15 ± 0.01* (0.71) −6.29 ± 0.26* −0.38 ± 0.01* (0.42)
WIN 62,577 −5.35 ± 0.05* −0.39 ± 0.01* (0.40) −5.60 ± 0.05* −0.60 ± 0.01* (0.25)
  • * Student's t test found a significant (p < 0.05) difference between WIN 51,708 and WIN 62,577 parameters.

  • Student's t test found a significant (p < 0.05) difference between M1 and M4 mAChR groups.