Valproic acid: metabolite concentrations in plasma and brain, anticonvulsant activity, and effects on GABA metabolism during subacute treatment in mice.

  • 1 May 1982
    • journal article
    • Vol. 257  (1) , 20-31
Abstract
Mice were continuously treated with valproic acid (VPA) via the drinking water for period from 1 to 12 days. The daily drug intake varied between 500 and 580 mg/kg. However, due to the rapid elimination of VPA in this species average plasma concentrations of only 3-4 micrograms/ml VPA were present at 8:30 a.m., the time chosen for determinations. In the brain, VPA levels were about 10% of those in plasma. In regard to VPA metabolism the products of beta-oxidation 2-en-VPA 2-propyl-2-pentenoic acid) and 3-keto-VPA (2-propyl-3-oxopentanoic acid) proved to be the main metabolites in plasma although other (minor) metabolites of VPA were also present. The only metabolite of VPA detected in the brain was 2-en-VPA. VPA medication caused a significant increase in the threshold for electroconvulsions which was associated with a slight increment of brain GABA levels. The activity of glutamic acid decarboxylase was significantly elevated whereas GABA aminotransferase was not affected. After withdrawal of VPA, a delayed effect on seizure threshold was observed which extended to time periods where VPA could no longer be detected in the brain, but 2-en-VPA was still present.

This publication has 0 references indexed in Scilit: