Fig. 9.

Estimation of allosteric modulator cooperativity and affinity values from potency curves. A and B, allosteric modulator potency curves were determined for the indicated positive allosteric modulators in the presence of an EC₂₀ concentration of glutamate. CPPHA and VU0364289 both achieved maximal responses to glutamate; therefore, logβ values were constrained to equal the average maximal leftward shift in the glutamate concentration-response curves (Table 6) for estimations of pK_B. For all other PAMs, both logβ and pK_B values were determined through nonlinear regression analyses. C, negative allosteric modulators were assessed for their ability to inhibit a submaximal glutamate response. D, affinity estimates from potency curves (y-axis) and from progressive fold-shift analyses (x-axis) for PAMs (●) and NAM (○) showed strong correlation. E, strong correlation was observed between logβ values estimated through nonlinear regression from modulator potency curves (y-axis) and from progressive fold-shift analyses (x-axis). Data represent the mean ± S.E.M. from at least three independent determinations. Error bars not shown lie within the dimensions of the symbols. Dashed line, unity.