TABLE 1

Empirical and operational model parameter estimates for the orthosteric ligands in mediating the IP1 accumulation via activation of the M1 mAChR in FlpInCHO-hM1 cells

Concentration-response curves for orthosteric ligands were established in the absence or presence of PBZ pretreatment (followed by extensive washout). Data were fitted using the operational model (eq. 1) to determine the functional affinity (pKA) and operational efficacy (logτ) values. Parameter values are the mean ± S.E.M. of eight independent experiments with repeats in duplicate. Data were analyzed by one-way ANOVA (with α = 0.01) using a Dunnett multiple comparisons test, where *P < 0.05 was considered to be significantly different to those of the endogenous agonist ACh.

LigandpEC50aEmaxbpKAcLogτAdτAe
ACh5.79 ± 0.0799.7 ± 2.95.26 ± 0.230.55 ± 0.293.6
Ixo7.97 ± 0.09*101.3 ± 3.36.99 ± 0.17*1.03 ± 0.23*10.7
Oxo-M6.08 ± 0.1390.3 ± 4.85.35 ± 0.280.66 ± 0.40*4.6
Xan6.96 ± 0.21*29.8 ± 2.7*6.48 ± 0.51*−0.31 ± 1.3*0.5
  • a Negative logarithm of the EC50 value of the vehicle-pretreated control curve.

  • b Maximal agonist response under the vehicle-pretreated conditions, relative to ACh.

  • c Negative logarithm of the functional affinity value constant KA, derived using eq. 1.

  • d Logarithm of the operational efficacy parameter for the orthosteric agonist in the absence of PBZ-pretreatment derived using eq. 1.

  • e Antilogarithm of the operational efficacy parameter.