Barbiturates allosterically inhibit GABA antagonist and benzodiazepine inverse agonist binding

Research output: Contribution to journalArticle

Abstract

Barbiturates and the related depressant drugs, etazolate and etomidate, inhibited both the binding of [3H]bicuculline methochloride (BMC) to γ-aminobutyric acid (GABA) receptor sites and the binding of [3H]β-carboline-3-carboxylic acid methyl ester (βCCM) to benzodiazepine receptor sites in mammalian brain. These concentration-dependent effects were chemically specific and stereospecific in a manner correlating with the activity of barbiturates to enhance GABA responses in neurons and to enhance GABA and benzodiazepine receptor agonist binding in vitro. The barbiturate inhibition of [3H]BMC binding involved a decrease in affinity which at high concentrations of barbiturates results in an effective complete loss of detectable binding. The maximal inhibition of [3H]βCCM binding involved a more modest decrease in affinity (increase in KD from 1.35 to 1.85 nM). The barbiturate inhibitions of both ligands could be reversed by picrotoxin, suggesting an indirect action at previously defined picrotoxin/barbiturate modulatory sites on the GABA-benzodiazepine receptor/chloride ion channel complex.

Details

Authors
External organisations
  • University of California, Riverside
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Barbiturates, Benzodiapines, Chloride ion channels, CNS depressants, GABA receptors
Original languageEnglish
Pages (from-to)205-212
JournalEuropean Journal of Pharmacology
Volume102
Issue number2
Publication statusPublished - 1984 Jul 13
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes