BIOLOGICAL ACTIONS In vivo AND In vitro OF TWO γ‐AMINOBUTYRIC ACID (GABA) ANALOGUES: β‐CHLORO GABA AND β‐PHENYL GABA

Abstract

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