Does glycine antagonism underlie the excitatory effects of methohexitone and propofol

S. J. Dolin*, M. B. Smith, J. Soar, P. J. Morris

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)

Abstract

We have investigated the pharmacological basis of CNS excitation that occurs in association with general anaesthesia in mice. Propofol produced sustained clonic movements during anaesthesia. Methohexitone produced intermittent non-rhythmic jerking during anaesthesia. Ethanol and pento-barbitone produced anaesthesia without associated clonic movements. Doses of all anaesthetic drugs were equipotent. Surface EEG recordings showed paroxysmal discharges consistent with interictal manifestations of cortical seizures with methohexitone or propofol, but not with ethanol or pentobarbitone. Strychnine, a glycine antagonist without effects on the cerebral cortex, and bicucul-line, a GABAA antagonist with effects on the cerebral cortex, were used in doses that were equipotent-0.5 log units less than the ED10 for clonic convulsions. Strychnine potentiated both excitatory behaviour and EEG paroxysmal discharges when given with methohexitone or propofol, but not with ethanol or pentobarbitone. Bicuculline did not affect either behaviour or EEG with any of the anaesthetic drugs. Our data show that methohexitone and propofol produced CNS excitation, while pentobarbitone and ethanol did not. We propose that the pharmacological basis of this excitation may be glycine antagonism occurring in subcortical structures.

Original languageEnglish
Pages (from-to)523-526
Number of pages4
JournalBritish Journal of Anaesthesia
Volume68
Issue number5
DOIs
Publication statusPublished - May 1992

Bibliographical note

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • Anaesthetics
  • Complications: excitatory phenomenon
  • Intravenous: methohexitone
  • Propofol

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