Behavioral effects of vigabatrin correlated with whole brain gamma-aminobutyric acid metabolism in audiogenic sensitive rats

Arzneimittelforschung. 1998 Jul;48(7):713-6.

Abstract

The present study evaluates dose-dependent behavioral effects of acutely or subacutely administered single doses of vigabatrin (gamma-vinyl gamma-aminobutyric acid, gamma-vinyl GABA, CAS 60643-86-9) in audiogenic sensitive rats, in correlation with whole brain GABA metabolism. There was a discrepancy in timing between behaviorally observed maximal antiepileptic protection (4 h after i.p. administration of gamma-vinyl GABA) and on the other hand maximal inhibition of GABA-transaminase activity and maximal increase of whole brain GABA content (24 h after i.p. administration of gamma-vinyl GABA). This suggests that the antiepileptic properties of gamma-vinyl GABA not only depend on GABA-ergic neurotransmission. A possible explanation is a gamma-vinyl GABA-induced decrease of excitatory amino acids or increased glycine concentrations in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobutyrate Transaminase / metabolism
  • Acoustic Stimulation*
  • Animals
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects*
  • Brain Chemistry / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Rats
  • Rats, Wistar
  • Seizures / metabolism*
  • Vigabatrin
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Anticonvulsants
  • gamma-Aminobutyric Acid
  • 4-Aminobutyrate Transaminase
  • Vigabatrin