. Author manuscript; available in PMC: 2018 Apr 19.

Published in final edited form as: ACS Chem Neurosci. 2017 Jan 10;8(4):866–883. doi: 10.1021/acschemneuro.6b00429

Table 6.

Mouse M₁ PAM Potency Coupled with Mouse CNS Penetration

compd	mM₁ EC₅₀ (nM)^a	mM₁ pEC₅₀	mACh Max (%)^a	Mouse K_p (K_p,uu)^b
28a	155	6.81 ± 0.03	79 ± 1	4.84 (2.61)
28c	263	6.58 ± 0.02	77 ± 1	ND
16	46	7.34 ± 0.02	79 ± 1	0.21 (0.16)
31	83	7.08 ± 0.02	73 ± 1	ND
32	46	7.34 ± 0.02	75 ± 2	0.21 (0.16)
33	23	7.63 ± 0.02	78 ± 1	ND

Calcium mobilization assays with mM₁-CHO cells performed in the presence of a fixed EC₂₀ fixed concentration of acetylcholine. Values are the average of at least three independent determinations performed in triplicate ± SEM.

Total and calculated unbound brain:plasma partition coefficients determined at 0.25 h post-administration of a discrete dose of compound (10 mg/kg, i.p.) to male mice (n = 3 or 4), in conjunction with in vitro mouse plasma protein and brain homogenate binding assay data.