and effects on brain GABA metabolism of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based inactivator of γ-aminobutyric acid transaminase
1983; Elsevier BV; Volume: 32; Issue: 24 Linguagem: Inglês
10.1016/0024-3205(83)90391-0
ISSN1879-0631
AutoresRichard B. Silverman, A. Jabbar Muztar, Mark A. Levy, James D. Hirsch,
Tópico(s)Biochemical effects in animals
ResumoThe 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.
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