title: Neither GABA(A) nor strychnine-sensitive glycine receptors are the sole mediators of MAC for isoflurane.
abstract: Inhaled anesthetics produce immobility (a cardinal aspect of general anesthesia) by an action on the spinal cord, possibly by potentiating the responses of gamma-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%.
  
  
  CONCLUSIONS
  gamma-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).
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143-0464, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: J M
authors.initials: JM
authors.lastname: Sonner
mesh_terms: D000042:Absorption; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D007530:Isoflurane / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008751:Methylene Blue / Q000493:pharmacokinetics / Q000494:pharmacology; D010852:Picrotoxin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects; D013331:Strychnine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018685:Anesthetics, Inhalation; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D007530:Isoflurane; D008751:Methylene Blue; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013331:Strychnine