Effect of Drugs on Human Erythrocytes.V. : Inhibition of Cellular Metabolism and Adenosine Triphosphatase Activity by Drugs and Relation of the Inhibition to Drug-induced Hemolysis

In an attempt to clarify the effects of drugs on the metabolism, transport mechanism and life time of human erythrocytes, the effects of chlorpromazine and clemastine on the ATP content, sodium pump and glucose-6-phosphate (G-6-P) dehydrogenase were studied. Chlorpromazine at 2 and 3×10-4M caused only a 5% reduction in the ATP level of erythrocytes and the drug at 8×10-4 and 10-3M induced 20 and 22% decreases in the amount of the ghost membrane, respectively. The incubation of erythrocytes in an ATP-generating system had only a slight protective effect against the drug-induced hemolysis. The Na+, K+-ATPase activity in the ghost membrane was markedly decreased by chlorpromazine at 6×10-4 to 10-3M without inhibition of Mg2+-ATPase activity, and inhibition of the Na+, K+-ATPase activity was observed a short time after the drug treatment. There was also a partial inhibition of G-6-P dehydrogenase activity by the drugs. Complete inhibition of Na+, K+-ATPase activity with ouabain resulted in no increment of the directly drug-induced hemolysis and no extreme shape changes. Therefore, the directly drug-induced hemolysis is not necessarily an energy-dependent process. However, the cells exposed to chlorpromazine at prelytic concentrations were gradually hemolyzed upon prolonged incubation in isotonic solution at 37°. Consequently, the drug treatment appears to shorten the survival time of the cells, probably due to inhibition of cellular metabolism and to membrane damage.