BIOCHEMICAL EFFECTS OF THE ANTICONVULSANTS TRIMETHADIONE, ETHOSUXIMIDE AND CHLORDIAZEPOXIDE IN RAT BRAIN

— The concentrations of several metabolites, including glucose, glycogen, hexose phosphates, adenine nucleotides phosphocreatine, amino acids and some tricarboxylate cycle intermediates, have been estimated in cerebral tissues of rats treated with anticonvulsant doses of trimethadione, ethosuximide and chlordiazepoxide. Anticonvulsant administration, in each case, produced an increase in brain glucose, but only trimethadione and ethosuximide resulted in elevated brain/blood glucose ratios. It was concluded that the apparent rise in intracellular glucose with the latter drugs may, in part, be the result of a stimulation of glucose transport from blood into the brain. Anticonvulsant administration was also shown to result in a depression of some tricarboxylate cycle intermediates. The pattern of these metabolite changes was in effect similar to those reported independently in mice treated with anaesthetics and it was therefore concluded that these differences probably reflected a depression in metabolic rate. Metabolic alterations in general do not indicate aetiology but rather effects of the drug activities. However, a role implicating increased intracellular glucose levels with membrane stabilization is discussed.