Passage of pyridinium oximes into human red cells

Abstract

Contrary to popular views, pralidoxime chloride, a positively charged oxime and a drug used to treat poisoning from organophosphorus insecticides, penetrates the red cell membrane. Two other therapeutically related drugs that have similar dissociation constants and chemical function groupings penetrate to negligible extents. Pralidoxime chloride did not bind to either red cell stroma or hemoglobin. The rate of entry into red cells by pralidoxime chloride did not change when the pH of blood was changed by ± 0.6 pH unit. Since the rate of entry of pralidoxime chloride into red cells from plasma was identical to the rate at which oxime passed from red cells into plasma, the process was likely due to simple diffusion. In addition, the fraction of pralidoxime chloride entering the red cells was independent of drug concentration. The penetration was not affected by active transport inhibitors, such as ouabain or N-methyl maleimide. The selective penetration could not be related to lipid solubility.