Propofol-Induced Anesthesia in Mice Is Mediated by [gamma]-Aminobutyric Acid-A and Excitatory Amino Acid Receptors.
Irifune, Masahiro DDS, PhD *; Takarada, Tohru DDS, PhD *; Shimizu, Yoshitaka DDS *; Endo, Chie DDS *; Katayama, Sohtaro DDS *; Dohi, Toshihiro PhD +; Kawahara, Michio MD, PhD *
[Report] Anesthesia & Analgesia. 97(2):424-429, August 2003.

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To elucidate the role of [gamma]-aminobutyric acid (GABA)A receptor complex and excitatory amino acid receptors (N-methyl-d-aspartate [NMDA] and non-NMDA receptors) in propofol-induced anesthesia, we examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol anesthesia in mice. All drugs were administered intraperitoneally. General anesthetic potencies were evaluated using a righting reflex assay. The GABAA receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diazepam and the NMDA receptor antagonist MK-801 augmented propofol anesthesia, but the non-NMDA receptor antagonist CNQX did not. In contrast, the GABAA receptor antagonist bicuculline antagonized propofol (200 mg/kg; 95% effective dose for loss of righting reflex) induced anesthesia. However, neither the benzodiazepine receptor antagonist flumazenil, the GABA synthesis inhibitor l-allylglycine, nor the NMDA receptor agonist NMDA reversed propofol anesthesia. Conversely, the non-NMDA receptor agonist kainate enhanced propofol anesthesia. These results suggest that propofol-induced anesthesia is mediated, at least in part, by both GABAA and excitatory amino acid receptors.

(C) 2003 International Anesthesia Research Society