TABLE 3

Summary of operational model parameters for negative allosteric modulation of glutamate-mediated intracellular Ca²⁺ mobilization in HEK cells expressing low and high mGlu₅ levels

Parameters are defined and quantification was performed as for Table 2. Estimates of glutamate coupling efficiency (logτ_A), transduction coefficient (n), maximal system response (E_m), and basal response levels are presented in Supplemental Table 2. Data represent the mean ± S.E.M. from at least three independent determinations.

Cell Line/Parameter	MPEP	M-5MPEP	VU0285683	VU0366248	VU0366249	VU0366058
Low-level mGlu₅ α unconstrained
pK_B	8.44 ± 0.12	6.99 ± 0.14	7.40 ± 0.17	6.62 ± 0.13	6.36 ± 0.08	6.71 ± 0.20
logβ	−100^{^a}	−0.75 ± 0.05	−100^{^a}	−0.83 ± 0.10	−0.59 ± 0.08	−100^{^a}
logα	0.12 ± 0.06	0.25 ± 0.07	0.20 ± 0.11	−0.04 ± 0.14	0.25 ± 0.12	0.41 ± 0.14
Low-level mGlu₅ α = 1
pK_B	8.55 ± 0.09	7.04 ± 0.15	7.59 ± 0.10	6.63 ± 0.08	6.35 ± 0.08	7.09 ± 0.10
logβ	−100^{^a}	−0.72 ± 0.05	−100^{^a}	−0.90 ± 0.09	−0.52 ± 0.10	−100^{^a}
High-level mGlu₅
pK_B	8.53 ± 0.03	7.14 ± 0.08	7.55 ± 0.06	6.72 ± 0.07	6.58 ± 0.04	6.69 ± 0.07
logβ	−100^{^a}	−100^{^a}	−100^{^a}	−100^{^a}	−0.48 ± 0.04	−100^{^a}

↵a For NAMs that abolished the response to glutamate, β = 0 was assumed and therefore logβ was constrained to −100.