Approaches to the study of drug interactions in behavioral pharmacology.

This paper discusses some of the approaches which have been used for analyzing drug interactions with an emphasis on applications for behavioral pharmacology. Two broad categories of drug interactions are defined: heterergic, when only one of the drugs is active in the behavioral measure employed, and homergic, when both of the interacting drugs have similar action. Two distinct models are presented for homergic drug interactions. The effect-addition model predicts that the combined action of two drugs is equal to the arithmetic sum of the individual effects. This is referred to as effect-additive and deviations from the predicted effects are described accordingly. The dose-addition model takes both dose and effect into account, and thus has a sounder theoretical basis. Leftward shifts in the dose-effect curves are described as equal to (dose-additive), or greater than (supra-additive) or less than (infra-additive) predicted on the basis of the relative potencies of the interacting drugs. Isobolographic methods facilitate data reduction and allow a graphic depiction of dose-addition analysis. A survey of the literature utilizing isobolographic techniques is presented.