Glycine Receptors Mediate Part of the Immobility Produced by Inhaled Anesthetics

• Published in: Anesthesia and analgesia Vol. 96; no. 1; pp. 97 - 101
• Main Authors: Zhang, Yi, Laster, Michael J, Hara, Koji, Harris, R Adron, Eger, Edmond I, Stabernack, Caroline R, Sonner, James M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.01.2003; Lippincott
• Subjects: Anesthetics, Inhalation - pharmacokinetics; Anesthetics, Inhalation - pharmacology; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Chromatography, Gas; Cyclopropanes - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Female; Glycine Agents - pharmacology; Halothane - pharmacology; Injections, Spinal; Isoflurane - pharmacokinetics; Isoflurane - pharmacology; Male; Medical sciences; Movement - drug effects; Neuropharmacology; Oocytes - drug effects; Oocytes - metabolism; Pharmacology. Drug treatments; Pulmonary Alveoli - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Glycine - drug effects; Strychnine - pharmacology; Xenopus; Volatile compound; Rat; Rodentia; Halothane; General anesthesia; Intrathecal administration; Isoflurane; Inhalation; Vertebrata; Mammalia; General anesthetic; Minimal alveolar concentration; Cyclopropane; Animal; Glycine receptor; Antagonist; Mechanism of action; Halogen Organic compounds
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-200301000-00021

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 systemshalothane (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 (r = 0.82). These results support the hypothesis that glycine receptors mediate part of the immobilization produced by inhaled anesthetics.