TABLE 1

[3H]QNB inhibition binding (pKI) and Ca2+ mobilization potency (pEC50) parameters for various ligands at the M1 WT and DREADD mAChRs

Estimated parameter values represent the mean ± S.E. of three experiments performed in duplicate.

M1 WTM1 DREADD
LigandpKIapEC50bpKIpEC50
ACh3.86 ± 0.048.54 ± 0.062.43 ± 0.07*3.74 ± 0.12*
Xanomeline6.84 ± 0.028.38 ± 0.065.10 ± 0.03*5.83 ± 0.07*
TBPB6.76 ± 0.087.86 ± 0.106.45 ± 0.097.30 ± 0.19
McN-A-3434.71 ± 0.087.54 ± 0.054.37 ± 0.105.39 ± 0.08*
CNO5.18 ± 0.075.95 ± 0.075.93 ± 0.04*8.87 ± 0.07*
Clozapine6.81 ± 0.077.14 ± 0.407.93 ± 0.08*9.30 ± 0.07*
NDMC6.60 ± 0.057.49 ± 0.097.40 ± 0.02*9.33 ± 0.08*
BQCA4.15 ± 0.118.02 ± 0.064.05 ± 0.134.16 ± 0.16*

  • ↵a Negative logarithm of the equilibrium dissociation constant for each ligand.

  • ↵b Negative logarithm of the EC50.

  • ↵* Significantly different (P < 0.05), two-tailed Students t-test, from the corresponding parameter at the M1 WT mAChR.