Inhibition by methylphenidate of transport across the yeast cell membrane.

The influence of methylphenidate on glycolysis in yeast cells was studied to describe more fully the nature of the reactions in which this drug participates. CO(2) production and O(2) uptake of yeast cells was inhibited 75% by a 10 mm concentration of the compound. This effect, with glucose as a substrate, occurred at pH 7.0, but not at pH 4.5. Kinetic data indicated that the reaction was noncompetitive and complex; the methylphenidate effect on CO(2) production could not readily be reversed. Glycolysis by cell-free extracts was not inhibited at the 10-mm concentration, but was affected at 100 mm. Utilization of O(2) with maltose and ethyl alcohol as substrates also was reduced. Entry into the cells of a number of different carbohydrates and of glycine was inhibited to different degrees. The loss from suspended cells of materials absorbing at 280 nm was reduced, and the efflux of sorbose, arabinose, and lactose was decreased. Thus, transport into and out of the cells was inhibited and leakage, or permeability, was reduced. It is hypothesized that methylphenidate reacts with a cell membrane constituent, or constituents, and inhibits glycolysis by blocking sugar passage.