The drug-receptor complex

Abstract

The rate of association of drug and receptor when limited by diffusion alone will correspond to a basic rate of 2·5 × 109 litres/mole sec and will have a net activation energy of 3–4 kcal/mole. This rate will not be significantly increased by attractive forces between drug and receptor but could be reduced by repulsive forces. It could be considerably reduced by the presence of bound water and ions, by the requirement of activation energy for combination and by geometrically restricted access to the receptor. Complex formation is due to the stabilisation of the drug in the force field from which it can escape only on acquisition of kinetic energy greater than the potential energy of the field; the fraction of molecules acquiring this threshold kinetic energy can be calculated from the Boltzman equation. The rate of dissociation of the complex is the rate of loss by free diffusion multiplied by the Boltzman factor. The lifetime of drug receptor complexes is long enough to enable molecules undergoing collision in the non-ideal aspect or conformation time to present in the ideal state.