title: Inhaled anesthetics do not combine to produce synergistic effects regarding minimum alveolar anesthetic concentration in rats.
abstract: BACKGROUND
  We hypothesized that pairs of inhaled anesthetics having divergent potencies [one acting weakly at minimum alveolar anesthetic concentration (MAC); one acting strongly at MAC] on specific receptors/channels might act synergistically, and that such deviations from additivity would support the notion that anesthetics act on multiple sites to produce anesthesia.
  
  
  METHODS
  Accordingly, we studied the additivity of MAC for 11 anesthetic pairs divergently (one weakly, one strongly) affecting a specific receptor/channel at MAC. By "divergently," we usually meant that at MAC the more strongly acting anesthetic enhanced or blocked the in vitro receptor or channel at least twice (and usually more) as much as did the weakly acting anesthetic. The receptors/channels included: TREK-1 and TASK-3 potassium channels; and gamma-aminobutyric acid type A, glycine, N-methyl-D-aspartic acid, and acetylcholine receptors. We also studied the additivity of cyclopropane-benzene because the N-methyl-D-aspartic acid blocker MK-801 had divergent effects on the MACs of these anesthetics. We also studied four pairs that included nitrous oxide because nitrous oxide had been reported to produce infraadditivity (antagonism) when combined with isoflurane.
  
  
  RESULTS
  All combinations produced a result within 10% of that which would be predicted by additivity except for the combination of isoflurane with nitrous oxide where infraadditivity was found.
  
  
  CONCLUSIONS
  Such results are consistent with the notion that inhaled anesthetics act on a single site to produce immobility in the face of noxious stimulation.
authors.affiliation: Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464, USA. egere@anesthesia.ucsf.edu
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
authors.forename: Michael
authors.initials: M
authors.lastname: Tang
authors.forename: Mark
authors.initials: M
authors.lastname: Liao
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
authors.forename: Pamela
authors.initials: P
authors.lastname: Flood
authors.forename: Andrew
authors.initials: A
authors.lastname: Jenkins
authors.forename: Douglas
authors.initials: D
authors.lastname: Raines
authors.forename: Jan F
authors.initials: JF
authors.lastname: Hendrickx
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shafer
authors.forename: Tanifuji
authors.initials: T
authors.lastname: Yasumasa
authors.forename: James M
authors.initials: JM
authors.lastname: Sonner
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D007103:Immobilization; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D024683:Potassium Channels, Tandem Pore Domain; D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; C103742:potassium channel protein TREK-1; D007530:Isoflurane; D009609:Nitrous Oxide