Comparison of the effects of valproate, ethosuximide, phenytoin, and pentobarbital on cerebral energy metabolism in the rat.

The acute effects of valproate (200 and 400 mg/kg), ethosuximide (200 and 400 mg/kg), phenytoin (25 and 50 mg/kg), and pentobarbital (30 and 60 mg/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral content of energy metabolites and by evaluating the rate of metabolite utilization following decapitation. The treatments did not affect the levels of phosphocreatine (PCr), ATP, ADP, and AMP, but did enhance the glycogen or glucose stores. Pentobarbital induced a decrease in lactate, whereas valproate led to a decrease in pyruvate and an increase in lactate. Calculation of the metabolite fluxes after decapitation showed that all treatments delayed the rate of ATP utilization. The response was dose-dependent except with valproate. In addition, pentobarbital led to reductions in glucose utilization and lactate production, but the other drugs had no significant effect on glycolysis rate. The sparing effect on ATP utilization may be related to a membrane-stabilizing effect and may provide brain protection in case of excessive neuronal activation.