3-Alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents

Charles P. Taylor, Mark G. Vartanian, Ryszard Andruszkiewicz, Richard B. Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Recently we showed that 3-alkyl-4-aminobutanoic acids are in vitro activators of brain l-glutamic acid decarboxylase (GAD) that show anticonvulsant activity. Since activation of GAD leads to increased concentrations of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in vitro, these compounds could represent a new class of anticonvulsant agents. Here it is shown that 3-alkylglutamic acid analogues also activate GAD and that all of the compounds in both series are active anticonvulsant agents against low intensity electroshock in mice. The most active compound, 3-isobutyl GABA, was tested further against maximal electroshock in mice and was shown to be very potent after both intravenous and oral administration without causing ataxia. It is not known if brain GABA levels are elevated in vivo by administration of these compounds or if the mechanism of anticonvulsant activity is related to their ability to activate GAD.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalEpilepsy Research
Volume11
Issue number2
DOIs
StatePublished - Apr 1992

Keywords

  • Anticonvulsants
  • GABA analogues
  • Glutamic acid analogues
  • l-Glutamic acid decarboxylase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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