COMPARATIVE EFFECTS OF VALPROATE AND THE NEW EXPERIMENTAL ANTICONVULSANT DRUG ALPHA-ETHYL-ALPHA-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 blo cking seizures induced by convulsant compounds and maximal electric sh ock 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 s ingle therapeutic dose of the two drugs on levels of key metabolites i n the blood, liver, and brain of normal suckling infant mice. Unlike V PA, alpha-EMTBL had no adverse effects on selected aspects of liver ca rbohydrate, fat (ketogenesis), coenzyme A (CoA), carnitine, or amino a cid metabolism. In contrast to VPA, alpha-EMTBL did not alter concentr ations of neurotransmitter amino acids in brain. Coupled with the impr essive anticonvulsant activity of alpha-EMTBL in adult mice and its la ck of acute hepatotoxicity in infant mice, our findings support furthe r study of alpha-EMTBL as a potential adjunct to the relatively limite d armamentarium of effective antiepileptic drugs (AEDs) for clinical u se.