TABLE 2

Summary of effects of LY593093 and reference muscarinic agonist compounds on stimulation of GTPγ[³⁵S] binding activity in membranes prepared from CHO cells stably expressing human M1, M2, or M4 muscarinic receptors

Data were analyzed using nonlinear regression for a sigmoidal concentration-response curve (Prism version 4.0) and are expressed as mean ± S.E.M. from n ≥ 3 separate experiments. Potency data are expressed in log₁₀ molar (M) units, and efficacy data are expressed as a percentage of response at 10 μM oxotremorine M.

Compound	M1AChR		M2AChR		M4AChR
Compound	EC₅₀	E_max	EC₅₀	E_max	EC₅₀	E_max
	log₁₀ M	%	log₁₀ M	%	log₁₀ M	%
LY593093	−6.66 ± −7.50	94.3 ± 2.29	−5.97 ± −6.76	23.2 ± 1.39	>−5.00	^*
Acetylcholine	−7.59 ± −8.61	103 ± 1.86	−8.16 ± −9.31	101.7 ± 2.20	−7.28 ± −7.87	87.4 ± 3.88
Alvameline	>−4.52	^*	−6.53 ± −8.24	49.4 ± 2.33	>−4.52	^*
Sabcomeline	−7.25 ± −8.03	38.9 ± 2.18	−7.25 ± −8.18	89.9 ± 2.85	−7.17 ± −7.95	20.0 ± 1.41
Talsaclidine	−6.09 ± −7.04	69.3 ± 2.42	−6.07 ± −7.16	94.4 ± 2.47	−6.10 ± −7.03	21.6 ± 0.78
Xanomeline	−7.36 ± −8.13	63.7 ± 3.48	−7.11 ± −7.98	82.6 ± 3.12	−7.20 ± −7.77	46.1 ± 4.02

↵* <20% efficacy at the highest doses tested (10 μm for LY593093 and 30 μM for alvameline).