TABLE 1

[3H]QNB inhibition binding parameters for various ligands at the wild type (WT) and DREADD M4 mAChR.

Values represent the mean ± S.E.M. from n experiments performed in triplicate. ACh binding to the WT receptor could be resolved into two apparent dissociation constants. “High” and “Low” denote the negative logarithms of the apparent ligand dissociation constant for the high-and low-affinity states, respectively. Percentage high-affinity binding is shown in parentheses.


Ligand

M4 WT

M4 DREADD

n
pKB
nH
pKB
nH
ACh
High 4.9 ± 0.2 0.8 ± 0.1 3.2 ± 0.1 0.8 ± 0.1 6
(61 ± 23%)
Low 3.9 ± 0.4
Pilocarpine 4.3 ± 0.04 1.1 ± 0.1 3.4 ± 0.3* 0.8 ± 0.2 4
McN-A343 4.7 ± 0.1 0.9 ± 0.1 4.8 ± 0.1 0.7 ± 0.1 3
Clozapine 6.6 ± 0.1 0.8 ± 0.1 8.0 ± 0.1* 0.8 ± 0.2 6
CNO 4.9 ± 0.1 1.0 ± 0.3 6.6 ± 0.1* 0.8 ± 0.1 3
NDMC
6.0 ± 0.1
1.0 ± 0.1
7.4 ± 0.1*
1.2 ± 0.1
3
  • pKB, the negative logarithm of the apparent ligand dissociation constant; nH, Hill slope.

  • * Significantly different (P < 0.05) from the corresponding parameter at the M4 WT, as determined by Student's t test.