Effect of SRI-29574 on [3H]DA accumulation

[3H]DA uptake was assessed at various time points in the absence and presence of the indicated concentrations of SRI-29574. The combined data from all three experiments (Fig. 6A) (180 data points) were fit to the equation B = Emax × (T/(T + t1/2)), where B is the observed level of uptake, T is the time in minutes, and t1/2 is the time to half-maximal accumulation. The time course data for each drug condition were separately applied to the above equation, each of which differed only in the names of the corresponding parameters: Emax1, Emax2, Emax3, Emax4, and Emax5 and t1/2-1, t1/2-2, t1/2-3, t1/2-4, and t1/2-5. Thus, the unconstrained fit led to the reported parameter values. The data were then fit with the constraint that the Emax values were all equal. This resulted in a highly significant increase in the sum-of-squares (F = 18.9, P = 0). In contrast, fitting the data with the constraint that the t1/2 values were equal did not significantly increase the sum-of-squares (F = 0.46, P = 0.76).

[SRI-29574]t1/2EmaxInhibition of the Emax Value
032 ± 498 ± 40
128 ± 389 ± 411
427 ± 371 ± 2*29
834 ± 358 ± 2*42
2531 ± 343 ± 3*57
  • * P < 0.05 vs. control (unpaired Student's t test).