Comparative Effects of Valproate and the New Experimental Anticonvulsant Drug α‐Ethyl‐α‐Methyl‐Thiobutyrolactone on Selected Metabolite Levels in the Plasma, Livers, and Brains of Infant Mice

The newly discovered anticonvulsant drug, alpha-ethyl-alpha-methylthio butyrolactone (alpha-EMTBL),is as effective as valproate (VPA) in blocking seizures induced by convulsant compounds and maximal electric shock in adult mice. Other data have suggested that alpha-EMTBL might be less toxic than VPA and longer acting. We compared the effects of a single therapeutic dose of the two drugs on levels of key metabolites in the blood, liver, and brain of normal suckling infant mice. Unlike VPA, alpha-EMTBL had no adverse effects on selected aspects of liver carbohydrate, fat (ketogenesis), coenzyme A (CoA), carnitine, or amino acid metabolism. In contrast to VPA, alpha-EMTBL did not alter concentrations of neurotransmitter anticonvulsant activity of alpha-EMTBL in adult mice and its lack of acute hepatotoxicty in infant mice, our findings support further study of alpha-EMTBL as a potential adjunct to the relatively limited armamentarium of effective antiepileptic drugs (AEDs) for clinical use.