THE EFFECTS OF SOME NEWER ANAESTHETICS ON THE IN VITRO ACTIVITY OF GLUTAMATE DECARBOXYLASE AND GABA TRANSAMINASE IN CRUDE BRAIN EXTRACTS AND ON THE LEVELS OF AMINO ACIDS IN VIVO

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Abstract
—The effects of several anaesthetic and hypnotic compounds with well‐defined excitatory side‐effects on glutamate decarboxylase and γ‐aminobutyric acid transaminase activity have been examined. The dissociative anaesthetics ketamine and γ‐hydroxybutyric acid produced competitive inhibition of glutamate decarboxylase with respect to glutamate at concentrations which had no effect on GABA transaminase activity. The inhibitor constant (Ki) values were, ketamine: 13.3 mm, γ‐hydroxybutyric acid; 8.8 mm. The steroid anaesthetic alphaxalone was also a potent competitive inhibitor of glutamate decarboxylase Ki= 4.1 mm). Pentobarbitone, thiopentone and methohexitone non‐competitively inhibited both glutamate decarboxylase and GABA‐transaminase but only at high concentration (> 20 mm). None of the drugs tested produced any significant change in brain GABA or glutamate levels following the injection of an hypnotic or anaesthetic dose. It is proposed that an alteration in the rate of GABA synthesis as a result of the inhibition of glutamate decarboxylase could explain the convulsive properties of the dissociative anaesthetics when given at high doses.