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The effect of phenothiazine derivatives on growth, glucose uptake, and cell composition was studied in the ciliate protozoan Tetrahymena pyriformis W. The most effective inhibitor of growth in a chemically defined medium was promazine (PRZ), followed by chlorpromazine (CPZ), promethazine (PMZ), prochlorperazine (PCP), acetophenazine (ACP), and trifluoperazine (TFP). The uptake of glucose was highest in resting suspensions of cells in the logarithmic phase (40 hours), but decreased with increasing age of the culture. Little or no uptake of glucose occurred in cells pre-inhibited by PRZ or CPZ. The most effective inhibitor of glucose uptake was TFP, followed by ACP, PCP, PRZ, CPZ, and PMZ. The concentration of protein in cells grown with Tween 80 was unaffected by PRZ, although total cell populations were reduced. Under these conditions, PRZ or CPZ delayed the accumulation of lipid in the cells. Similarly, PRZ reduced the amount of RNA and DNA during the logarithmic phase.These results demonstrated that phenothiazine derivatives can influence lipid and nucleic acid levels in Tetrahymena, and further suggest that the drugs may interfere directly with the mechanism of glucose transport into the cell. These observations support the hypothesis that metabolic effects are related to the ability of phenothiazine derivatives to alter permeability of cell membranes.

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