Antagonist studies using the erythrocyte osmotic fragility membrane stabilization assay

d-Propoxyphene, diazepam, chloroquine and propranolol were studied in an erythrocyte membrane stabilization assay involving osmotic stress. d-Propoxyphene and diazepam appear to be considerably less potent membrane-stabilizing agents than propranolol; chloroquine showed the weakest membrane-stabilizing potency. All of the drugs exerted this effect on erythrocytes at concentrations, in buffer, similar to the plasma concentrations associated with severe toxicity or lethality in man. Neither caffeine nor l-histidine reversed the stabilization of the erythrocyte membrane by propranolol. Similarly, theophylline did not reverse the effects of d-propoxyphene. Chloroquine did not alter the membrane-stabilizing effects of diazepam but a low level of diazepam slightly enhanced the membrane-stabilizing effects of chloroquine. The erythrocyte osmotic fragility assay is a simple, sensitive assay for studying drug-induced membrane stabilization at concentrations similar to those occurring in human plasma in vivo. Antidotal reversal of membrane stabilization was not demonstrable in this model. This may be because this model tests the physical but not functional integrity of membranes, and suggests that the mode of action of antidotes to membrane-stabilizing agents should be examined in models for studying the functional capacities of cells or organisms.