The principle of nonspecificity and acute toxicity

It was over 80 years ago that activities of general anaesthetics were observed to be correlated with their liposolubility rather than their molecular structures. Other evidence followed in support of this view of drug 'nonspecificity'. However, in the last 20 years an overwhelming amount of data has been collected, which indicates that a pharmacological effect is always the result of a specific interaction between drugs and biochemical or biophysical processes. How can this apparently contradictory evidence be reconciled? To what extent should the physical properties of drugs be disregarded in determining their pharmacological potencies? We propose a scheme which allows specific and nonspecific drug interactions to coexist. It is a scheme which can account for these contradictions. It may also account for the discrepancies often found between affinity constants derived from binding experiments and from dose-response curves.