Biological actions in vivo and in vitro of two gamma-aminobutyric acid (GABA) analogues: beta-chloro GABA and beta-phenyl GABA

Br J Pharmacol. 1974 Nov;52(3):401-6. doi: 10.1111/j.1476-5381.1974.tb08609.x.

Abstract

1 The synthesis of two analogues of gamma-aminobutyric acid (GABA), beta-chloro GABA and beta-phenyl GABA is described.2 The activity of brain GABA aminotransferase was inhibited by beta-chloro GABA (5.7 x 10(-5)M) and beta-phenyl GABA (4.6 x 10(-3)M) in a competitive manner with GABA.3 beta-Chloro GABA exhibited 50% of the inhibitory activity of GABA in blocking the discharge of the crayfish stretch receptor neurone; beta-phenyl GABA had no detectable effect.4 Injection of beta-phenyl GABA (200 mg/kg) into normal or epileptic cats (cobalt) caused the appearance of synchronized slow-wave EEG activity.5 Administration of beta-chloro GABA (200 mg/kg) to epileptic cats (cobalt) produced a temporary diminution or abolition of epileptic discharges while causing no alteration in normal EEG activity.6 beta-Chloro GABA and beta-phenyl GABA had no effect on the concentrations of catecholamines or of amino acids in mouse brain.7 The results suggest that both beta-chloro GABA and beta-phenyl GABA may pass the blood-brain barrier.

MeSH terms

  • Amino Acids / analysis
  • Aminobutyrates / pharmacology*
  • Animals
  • Astacoidea
  • Brain / enzymology
  • Catecholamines / pharmacology
  • Electroencephalography
  • In Vitro Techniques
  • Mice
  • Reflex / drug effects
  • Transaminases / metabolism
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / chemical synthesis
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Amino Acids
  • Aminobutyrates
  • Catecholamines
  • gamma-Aminobutyric Acid
  • Transaminases