Molecular and systemic mechanisms of general anaesthesia: The 'multi-site and multiple mechanisms' concept

Christian Grasshoff, Uwe Rudolph, Bernd Antkowiak

Research output: Contribution to journalReview articlepeer-review


Purpose of review: Amnesia, hypnosis and immobility are essential components of general anaesthesia. This review highlights recent advances in our understanding of how these components are achieved at a molecular level. Recent findings: Commonly used volatile anaesthetic agents such as isoflurane or sevoflurane cause immobility by modulating multiple molecular targets predominantly in the spinal cord, including γ-aminobutyric acid A receptors, glycine receptors, glutamate receptors and TREK-1 potassium channels. In contrast, intravenously applied drugs such as propofol or etomidate depress spinal motor reflexes almost exclusively via enhancing γ-aminobutyric acidA receptor function. Studies on knock-in animals showed that etomidate and propofol act via γ-aminobutyric acidA receptors containing β3 subunits, whereas γ-aminobutyric acidA receptors including α2 and γ subunits mediate the myorelaxant properties of diazepam. These findings suggest that a large fraction of γ-aminobutyric acidA receptors in the spinal cord assemble from α2, β3 and most probably γ2 subunits. The hypnotic actions of etomidate are mediated by β3-containing γ-aminobutyric acidA receptors expressed in the brain. In contrast, γ-aminobutyric acidA receptors harbouring β2 subunits produce sedation, but not hypnosis. Furthermore, there is growing evidence that extrasynaptic γ-aminobutyric acid A receptors in the hippocampus containing α5 subunits contribute to amnesia. Summary: Clinical anaesthesia is based on drug actions at multiple anatomical sites in the brain. The finding that amnesia, hypnosis and immobility involve distinct molecular targets opens new avenues for developing improved therapeutic strategies in anaesthesia.

Original languageEnglish (US)
Pages (from-to)386-391
Number of pages6
JournalCurrent Opinion in Anaesthesiology
Issue number4
StatePublished - Aug 2005
Externally publishedYes


  • Amnesia
  • Anaesthetics
  • Hypnosis
  • Spinal cord
  • γ-aminobutyric acid receptor subtypes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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