Modification of GABA-mediated inhibition by various injectable anesthetics

Timothy E Albertson, W. F. Walby, R. M. Joy

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Increasing doses of the injectable anesthetics etomidate, Saffan, thiopental, ketamine, and xylazine and the vehicles saline and propylene glycol were administered to urethane-anesthetized rats. Their effects in vivo on perforant pathway-evoked field excitatory postsynaptic potentials and population spikes in the hippocampal dentate gyrus were determined. The primary purpose was to ascertain whether these compounds affect hippocampal excitability in a manner consistent with their proposed mechanisms of action. Compared with their respective vehicles, thiopental, etomidate, and xylazine reduced the amplitude of population spikes to single perforant pathway stimulation by 20-30% at the highest doses tested. Xylazine also increased the latency to onset of the population spike. No other effects were observed. Using paired pulse paradigms, it was determined that etomidate produced a dramatic, prolonged reduction in granule cell excitability at interpulse intervals of 10-100 ms. The magnitude of the effect was dose related and was reversible with the discontinuance of administration of the drug. Similar changes occurred with Saffan (althesin) and thiopental. Ketamine produced a small but significant depression in granule cell excitability during intervals of 10-200 ms. Xylazine had no effect. These data corroborate the importance of a prolongation of γ-aminobutyric acid A-mediated inhibition to the mechanism of actions of etomidate, thiopental, and Saffan at relevant exposure concentrations in vivo.

Original languageEnglish (US)
Pages (from-to)488-499
Number of pages12
JournalAnesthesiology
Volume77
Issue number3
StatePublished - 1992

Keywords

  • Anesthetics, intraperitoneal: Saffan (althesin); etomidate; ketamine; thiopental; xylazine
  • Brain, hippocampus: evoked potentials; perforant pathway

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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