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Effect of Diphenylhydantoin and a New Mechanism of Action

M. Gary Hadfield, MD

Arch Neurol. 1972;26(1):78-84.

Abstract
Diphenylhydantoin altered the uptake and binding of catecholamines in rat brain. This effect has not been reported previously. In synaptosomes, uptake of radioactively labeled norepinephrine was stimulated under anoxic conditions while uptake was inhibited under more physiologic conditions. In intact brain slices uptake of dopamine labeled with tritiated water was inhibited in caudate-putamen and stimulated in hypothalamus. Subcellular distribution studies of diphenylhydantoin labeled with carbon 14 showed differential binding of the drug to several subcellular fractions. The binding of diphenylhydantoin sodium to microsomes and synaptosomes may alter the synthesis or activity of ATPase, an enzyme controlling neurotransmitter uptake and binding. The effect of diphenylhydantoin on neurotransmitters appears to warrant additional investigation as a possible mechanism for the control of seizures by that drug.

Author Affiliations
New York and Richmond, Va

From the departments of pathology and psychiatry, New York University School of Medicine, New York, and the Department of Pathology, Division of Neuropathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Va.

Footnotes
Accepted for publication June 18, 1971.

Reprint requests to Division of Neuropathology, Medical College of Virginia, Box 17, Health Sciences Center, Richmond, Va 23219 (Dr. Hadfield).

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