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ANESTHETIC PHARMACOLOGY

Neither GABA_A nor Strychnine-Sensitive Glycine Receptors Are the Sole Mediators of MAC for Isoflurane

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence to James M. Sonner, MD, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464.

Inhaled anesthetics produce immobility (a cardinal aspect of general anesthesia) by an action on the spinal cord, possibly by potentiating the responses of -amino-n-butyric acid (GABA_A) and glycine receptors to GABA and glycine. In this study, we antagonized GABA_A and glycine responses by intrathecal administration of picrotoxin (a noncompetitive GABA_A antagonist), strychnine (a competitive glycine antagonist), or combinations of these drugs. We measured the capacity of antagonist infusion to increase isoflurane MAC (the minimum alveolar concentration of anesthetic that prevents movement in response to noxious stimuli in 50% of subjects). We found that these potent GABA_A and glycine receptor antagonists had a ceiling effect, either alone or in combination increasing the MAC of isoflurane by at most 47%.

Implications: -amino-n-butyric acid and glycine receptors may in part be responsible for the immobilizing action of isoflurane. They are not, however, the only receptors that contribute to isoflurane-induced immobility (i.e., that determine the MAC of isoflurane).

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