Effects of modification of the membranes of intact erythrocytes on the anti-haemolytic action of chlorpromazine.

Fresh human erythrocytes were washed and incubated at 37 degrees C in physiological saline buffered with Tris, containing calcium and either neuraminidase or trypsin or both enzymes together. Each enzyme alone, as well as both together, released similar amounts of sialic acids without haemolysis, apparently therefore from the same accessible sites on the surface of the cells. Exposure to neuraminidase or/and trypsin did not affect the osmotic fragility of red cells in hypotonic saline. The anti-haemolytic effect of low concentrations of chlorpromazine or thioridazine was diminished by previous exposure of red cells to neuraminidase and/or trypsin. The diminution in the anti-haemolytic effect of chlorpromazine was proportional to the release of sialic acids. The observations suggest that positively charged drugs such as chlorpromazine interact strongly with the negatively charged sialic acid moieties of glycoproteins on cell surfaces, removal of which increases the drugs' access to and disruption of the lipid bilayer in cell membranes.