Suppression of experimental barbiturate and phenytoin withdrawal syndrome using valproate sodium

A neuropharmacological study was performed to investigate the effect of valproate sodium (VS) used to suppress the barbiturate and phenytoin withdrawal syndrome induced experimentally in 1152 male Wistar rats. Valproate sodium was administered by mouth according to the following protocol: initial bolus dose of 400 mg/kg b.w. followed eight hours later by the first maintaining dose of 50 mg/kg b.w. This was given every 12 hours for five days. VS plasma levels were determined by gas chromatography. The therapeutic effect of valproate sodium was assessed by the seizure reactivity of the experimental and the control animals to an electroshock (50 mA/0.1 sec.). The results strongly indicate that valproate sodium inhibits the experimentally induced barbiturate and phenytoin withdrawal syndrome without causing drug dependance. It is suggested that some of the valproate sodium metabolites possess antiwithdrawal effect.