title: Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility.
abstract: BACKGROUND
  Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors.
  
  
  METHODS
  We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5% to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol.
  
  
  RESULTS
  Prebypass minimum alveolar concentration (MAC) for HFB was 0.82% +/- 0.14% (mean +/- sd); increased to 2.04% +/- 0.8% (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79% +/- 0.28% postbypass. Corresponding values for ODFB were 0.46% +/- 0.07%, 0.63% +/- 0.12% (P < 0.05), and 0.44% +/- 0.10%. ODFB MAC was 0.32% +/- 0.17% during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37% +/- 0.05%, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240%, but in one animal propofol requirements decreased, and the overall change was not statistically significant.
  
  
  CONCLUSIONS
  These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.
authors: Department of Anesthesiology and Pain Medicine, University of California, Davis, California 95616, USA. jfantognini@ucdavis.edu
authors: Joseph F
authors: JF
authors: Antognini
authors: Douglas E
authors: DE
authors: Raines
authors: Ken
authors: K
authors: Solt
authors: Linda S
authors: LS
authors: Barter
authors: Richard J
authors: RJ
authors: Atherley
authors: Emigdio
authors: E
authors: Bravo
authors: Michael J
authors: MJ
authors: Laster
authors: Katarzyna
authors: K
authors: Jankowska
authors: Edmond I
authors: EI
authors: Eger
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004569:Electroencephalography; D005464:Fluorobenzenes / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D006041:Goats; D006221:Halothane / Q000494:pharmacology; D007103:Immobilization; D009043:Motor Activity / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D005464:Fluorobenzenes; D005466:Fluorocarbons; C081153:1,2-difluorobenzene; C003005:hexafluorobenzene; D006221:Halothane; D015742:Propofol