[Skip to Content]
[Skip to Content Landing]
June 1970

Studies on the Mechanism of Action of Diphenylhydantoin

Arch Neurol. 1970;22(6):566-571. doi:10.1001/archneur.1970.00480240086012

IN EXPERIMENTS reported in 1955, Woodbury1 demonstrated in normal rats that the intracellular concentration of brain sodium was slightly diminished by diphenylhydantoin but that the uptake of sodium S24 into the brain was increased by this drug. These two facts taken together, he reasoned, could only be explained if diphenylhydantoin increased the rate of sodium flux from the intracellular space to the extracellular space. In these experiments, the chloride space was used to measure the extracellular compartment and intracellular sodium was calculated. In other experiments the drug was also shown to reduce intracellular sodium especially under circumstances of increased seizure susceptibility such ashyponatremia. The method of determining 24S flux could not distinguish neuronal from glial or extracellular accumulation, and the mechanism by which diphenylhydantoin caused increased cortical uptake of 24S is not clear from Woodbury's data; however, it has been supposed from this work that