In vitro and in vivo effects on brain GABA metabolism of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based inactivator of γ-aminobutyric acid transaminase

Richard B. Silverman*, A. Jabbar Muztar, Mark A. Levy, James D. Hirsch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The effects of intraperitoneal administration of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based covalent inactivator of γ-aminobutyric acid transaminase (GABA-T), on whole brain GABA metabolism in mice were investigated. A dose-dependent and time-dependent irreversible inactivation of GABA-T was observed with a concomitant increase in whole brain GABA levels. The compound exhibited no in vitro nor in vivo time-dependent inhibition of glutamate decarboxylase (GAD), alanine transaminase, or aspartate transaminase (Asp-T). It was, however, a potent competitive reversible inhibitor of GAD and a weak competitive inhibitor of Asp-T. The chloro analogue, (S)-4-amino-5-chloropentanoic acid, was ineffective.

Original languageEnglish (US)
Pages (from-to)2717-2723
Number of pages7
JournalLife Sciences
Volume32
Issue number24
DOIs
StatePublished - Jun 13 1983

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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