The location and chemical nature of drug ‘targets’ within the human erythrocyte membrane

Abstract

The cell membrane plays two important roles with respect to drug action. In the first place, the membrane as the initial site of contact of a drug with the cell is a highly probable target for its interaction and effect. In the second place, the membrane as the primary diffusion barrier of the cell determines how rapidly and by which routes the drug reaches the interior of the cell. Although the present discussion will deal primarily with the membrane as a target, the mode of ‘permeation’ must also be considered because only those membrane targets that can be reached by the drug can be affected. Some of the potential targets may be directly accessible on the outer surface of the cell, but others within the membrane structure can only be reached if they are located in the pathway through which the drug permeates. In assessing responses to drugs at the membrane level we must, therefore, consider two quite independent determinants. The first is the chemical specificity of the interactions of the drug with effector sites. The second, called ‘geographic specificity’ (Rothstein, 1970), is determined by the location of the effector sites in the membrane and the ability of the drug to reach them. Factors relating to diffusibility such as size, shape, charge, and lipid solubility are the predominant factors in the latter case, rather than chemical affinities.