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ANESTHETIC PHARMACOLOGY

Glycine Receptors Mediate Part of the Immobility Produced by Inhaled Anesthetics

Yi Zhang, MD^*, Michael J. Laster, DVM^*, Koji Hara, MD, R. Adron Harris, PhD, Edmond I. Eger, II, MD^*, Caroline R. Stabernack, MD^*, and James M. Sonner, MD^*

*Department of Anesthesia and Perioperative Care, University of California, San Francisco; University of Texas, Austin

Address correspondence and reprint requests to James M. Sonner, MD, Department of Anesthesia, S-455, University of California, San Francisco, San Francisco, CA 94143-0464. Address e-mail to sonnerj{at}anesthesia.ucsf.edu

Many inhaled anesthetics potentiate the effect of glycine on inhibitory strychnine-sensitive glycine receptors in vitro, supporting the view that this receptor could mediate the immobility produced by inhaled anesthetics during noxious stimulation (i.e., would underlie minimum alveolar anesthetic concentration [MAC]). There are quantitative differences between anesthetics in their capacity to potentiate glycine’s effect in receptor expression systems: halothane (most potentiation), isoflurane (intermediate), and cyclopropane (minimal). If glycine receptors mediate MAC, then their blockade in the spinal cord should increase the MAC of halothane more than that of isoflurane and isoflurane MAC more than cyclopropane MAC; the increases in MAC should be proportional to the receptor potentiation produced in vitro. Rats with chronically implanted intrathecal catheters were anesthetized with halothane, isoflurane, or cyclopropane. During intrathecal infusion of artificial cerebrospinal fluid, MAC was determined. Then MAC was re-determined during an infusion of 3, 12, 24, or 48 (isoflurane only) µg/min of strychnine (strychnine blocks glycine receptors) in artificial cerebrospinal fluid. Strychnine infusion increased MAC in proportion to the enhancement of glycine receptors found in vitro. The maximum effect was with an infusion of 12 µg/min. For the combined results at 12 and 24 µg/min of strychnine, the increase in MAC correlated with the extent of in vitro potentiation (r² = 0.82). These results support the hypothesis that glycine receptors mediate part of the immobilization produced by inhaled anesthetics.

IMPLICATIONS: In vitro, halothane potentiates glycine’s effect on strychnine-sensitive glycine receptors more than isoflurane and isoflurane more than cyclopropane. The present in vivo work indicates that antagonism of the glycine receptor with strychnine increases minimum alveolar anesthetic concentration for halothane more than isoflurane and isoflurane more than cyclopropane. Such results support the notion that glycine receptors may mediate part of the immobility produced by inhaled anesthetics.

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