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 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.
Thurston
J H
JH
Department of Neurology, Washington University School of Medicine, St. Louis Children's Hospital, USA.
Hauhart
R E
RE
D020155:3-Hydroxybutyric Acid; D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000833:Animals, Suckling; D000927:Anticonvulsants / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002331:Carnitine / Q000032:analysis; D003065:Coenzyme A / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006885:Hydroxybutyrates / Q000097:blood*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D000596:Amino Acids; D000927:Anticonvulsants; D001786:Blood Glucose; D006885:Hydroxybutyrates; C051894:alpha-ethyl, alpha-methyl-thiobutyrolactone; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D015107:4-Butyrolactone; D002331:Carnitine; D003065:Coenzyme A; D020155:3-Hydroxybutyric Acid