Table 1.

Pharmacological parameters of pyrazol-4-yl-pyridine 8–13 at the hM₄. Values represent the mean ± SEM obtained from three experiments conducted in duplicate.

Parameters	8	9	10	11	12	13
pKBa	6.4 ± 0.1	6.5 ± 0.1	6.5 ± 0.2	6.3 ± 0.1	6.4 ± 0.1	6.4 ± 0.1
LogαAChb	1.7 ± 0.3	1.7 ± 0.2	1.6 ± 0.2	1.4 ± 0.2	1.4 ± 0.1	1.6 ± 0.2
LogαβAChc	1.9 ± 0.2	2.0 ± 0.1	2.0 ± 0.2	1.9 ± 0.2	2.5 ± 0.1f	2.4 ± 0.2f
LogβAChd	0.1 ± 0.3	0.4 ± 0.3	0.4 ± 0.2	0.5 ± 0.3	1.1 ± 0.2	0.8 ± 0.2
Logτe	0.3 ± 0.0	0.4 ± 0.0	0.7 ± 0.0	0.5 ± 0.0	0.5 ± 0.0	0.6 ± 0.0

^aNegative logarithm of the equilibrium dissociation constant of M₄-PAMs.

^bLogarithm of the binding (α) cooperativity factor between M₄-PAMs and ACh.

^cLogarithm of the operational functional (αβ) cooperativity factors between ACh and M₄-PAMs.

^dLogarithm of the activation (β) cooperativity factors between ACh and M₄-PAMs, determined by subtracting (α) from the (αβ) parameters.

^eLogarithm of the operational efficacy parameter of M₄-PAMs as allosteric agonists.

^fSignificantly different (P < 0.05) from logα_ACh values as determined by a multiple unpaired t-test.