Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures
Figure 5
Isobologram for the antiabsence interaction between the GABAB antagonist CGP 36742 and the AMPA receptor antagonist LY 300164. The ED50 value of CGP 36742 is plotted on the ordinate (closed diamond) and that of LY 300164 on the abscissa (closed square). The ED50 values (for the inhibition of SWD) were obtained by fitting data to the sigmoid model, for the data from the time period 30–60-min after injection (see graph insert and Materials and Methods section of [135]). The straight line connecting the two plotted ED50 values is the isobolographic line, while dotted lines represent 95% confidence intervals (CIs). The experimental ED50 of the combination of CGP 36742 and LY 300164 (6 mg/kg) is plotted as the open circle and 95% CIs as the solid vertical line. If the experimentally determined ED50 lies on the isobolographic line, then the drug effects are additive. If the ED50 lies below this line, supra-additivity is assumed and when the ED50 lies above the isobolographic line, there is infra-additivity. However, when 95% CIs of the experimentally obtained combination overlap with the respective intervals of the isobolographic line, then the interaction is regarded as statistically nonsignificant. In such case, the observed interaction seems to be additive (reprinted with permission from Elsevier, [135]).
