Cooperativity in classical receptor theory.

Classical receptor-theory presents models of the relation between drug concentration and biological effect, also in the case where more than one binding site on a receptor must be occupied by the agonist to evoke a response. These models have considered only the possibility that none or all of these sites on the receptor are occupied by drug molecules; the possibility that receptors might by only partly occupied was disregarded. The present paper considers the consequences of this last possibility. It is concluded that the relation between concentration and effect, represented in different types of plots, is not determined only by the order of the reaction between the drugs and their receptors, but also by the ratios of the dissociation constants for the different steps of dissociation of the drug-receptor complex. This may make it almost impossible to make statements about the order of the reaction between drugs and receptors based on experimental data, and to discriminate between allosteric and classical receptor-theories.