Failure of diphenylhydantoin to prevent alcohol withdrawal convulsions in mice

Alcohol withdrawal reactions were induced in mice using an established technique. Mice, administered 1.0 mmole/kg pyrazole daily were exposed for 3 days to 10 mg/l ethanol vapor and withdrawal was brought about by discontinuation of the exposure. Diphenylhydantoin administered in doses of 12, 20 or 50 mg/kg by either of two routes (i.p. or p.o.), failed to have any discernable effect on the withdrawal. A 100 mg/kg dose of diphenylhydantoin increased seizure scores. Chloral hydrate administration in doses of 175, 244 or 350 mg/kg, on the other hand, lowered seizure scores in a manner which was dose related and prompt. These findings suggest that the clinical use of diphenylhydantoin for control of the seizures seen in alcohol withdrawal should be re-evaluated. The seizure scores of mice not exposed to ethanol but administered 1.0 mmole/kg pyrazole daily for 3 days were negligible and well within values obtained with naive control mice not exposed to any pharmacological agent.