TABLE 3

Summary of effects of LY593093 and reference muscarinic agonist compounds on displacement of N-methylscopalamine binding to membranes prepared from CHO cells stably expressing human M1–M5 muscarinic receptors

Nonspecific binding was measured in the presence of 1 μM atropine. Ki values were determined from the Cheng-Prusoff relationship Ki = IC50/1 + [ligand]/Kd, where IC50 is determined from a four-parameter fit of displacement curves, [ligand] = 1 nM [3H]NMS, and Kd is the equilibrium dissociation constant of [3H]NMS for each receptor determined by saturation binding experiments carried out by the membrane supplier. Data are expressed as the mean ± S.E.M. from n ≥ 3 separate experiments in log10 molar (M) units.

CompoundKi
M1AChRM2AChRM3AChRM4AChRM5AChR
log10 M
LY593093−6.21 ± −7.63−6.05 ± −7.54>−5.00>−5.00>−5.00
Alvameline−5.72 ± −6.67−6.49 ± −7.48−5.96 ± −6.88−5.33 ± −6.25−5.53 ± −6.48
Sabcomeline−7.69 ± −8.39−8.11 ± −8.75−7.91 ± −8.60−7.62 ± −8.36−7.72 ± −8.29
Talsaclidine−6.86 ± −7.69−7.76 ± −8.50−7.08 ± −8.14−6.95 ± −8.02−6.46 ± −7.51
Xanomeline−6.81 ± −7.92−7.16 ± −8.11−7.36 ± −8.23−7.24 ± −8.33−6.88 ± −8.10