Figure 9.

Fit of complex concentration-response data with the present model, Case I: Activity and binding data for a series of imidazoline-type α-adrenoceptor agonists (data after Ruffolo et al., 1979). (A) Fractional response as a function of log concentration for five compounds (symbols) fitted by the present model (Equation 4) using independently derived K _d values for binding affinity. Fitting of the response data is done by adjusting only one common γ (gain) and five individual ε (efficacy) parameters (Table S1.C). Fractional receptor occupancy data [calculated from the average K _d determined by two different methods (Ruffolo et al., 1979)] are also shown as dashed lines to highlight the ability of the model to account for the ligand-dependent mismatch between fractional response and occupancy. (B) Fractional response vs. occupancy data for these five compounds (symbols) and their corresponding fit with the present model fitted directly via the newly derived Equation 27. Note that the functional response can either exceed or lag behind the fractional occupancy data; for one compound (oxymetazoline), both occur depending on the ligand concentration.