Mapping and interpreting complex interactions between psychoactive drugs by simple computer-generated models.

Abstract

Drug combinations often yield results not readily predictable from those of their separate constituents. Computer programs have been developed to generate models of dual drug effects to analyse the results of experiments involving drug combinations. Single and combined dose-response results of rat locomotor activity are expressed as three-dimensional models. A manually plotted isobol diagram, showing eqi-active dose combinations of amylobarbitone and dexamphetamine, is compared with isobols constructed by the computer. A simple dose model theory is proposed which assumes that the two drugs have merely additive effects; differences between expectations from this theoretical model and the experimental results actually obtained were found by the computer. This computer approach allows detailed analysis of results. Three-dimensional dose response surfaces can provide a simple visual guide to dose combinations whose effects deviate significantly from those expected if the constituents were simply additive. Areas of special interest can thus be highlighted.