Effect of Valproate on In Vivo GABA-Turnover

  • Raymond Bernasconi
  • Markus Schmutz
  • Pierre Martin
  • Kathleen Hauser

Abstract

Valproate is an effective antiepileptic drug in animals (1) and man (2). Valproate raises brain GABA levels and biochemical studies have shown that it weakly inhibits the different enzymes related to the GABA catabolism, viz., 4-aminobutyrate: 2-oxoglutarate ami- transferase (E.C.2.6.1.19; GABA-T) (3) and succinic semialdehyde dehydrogenase (E.C.1.2.1.16) (4). It has been suggested that blockade of GABA catabolism is responsible for the increased GABA levels. On the other hand it has been proposed that valproate may enhance GABA synthesis by increasing L-glutamate-l-decarboxy- lase (E.C.4.1.1.15; GAD) activity and that this is the cause for the rise in GABA levels (5). The precise mechanism responsible for the GABA elevating effect of valproatein vivo remains to be clarified. The measure of GABA levels after inhibition of GABA-T and GAD could help to distinguish between two hypotheses. In this report, two major issues are addressed:
  1. a)

    What is the action of valproate on GABA turnover rate?

     
  2. b)

    Is the protection by valproate against convulsions induced by a reduction of GABA content, dependent on a normalization of GABA concentration?

     

Keywords

Phenol Vinyl Valproate Transferase Lism 

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Raymond Bernasconi
    • 1
  • Markus Schmutz
    • 1
  • Pierre Martin
    • 1
  • Kathleen Hauser
    • 1
  1. 1.Research Laboratories Pharmaceuticals DivisionCIBA-GEIGY LtdBasleSwitzerland

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