title: Convulsant activity of nonanesthetic gas combinations.
abstract: Most nonanesthetics (inhaled compounds that neither cause anesthesia when given alone nor decrease the partial pressure of a known inhaled anesthetic required to produce anesthesia) and transitional compounds (inhaled compounds that are less potent than would be predicted by the Meyer-Overton hypothesis) cause convulsions. A possible exception is the perfluoroalkane series of nonanesthetics. The present study tested whether perfluoroalkanes do provide an exception. Further, we tested whether the convulsant effects of nonanesthetic and transitional compounds were additive. The nonanesthetic perfluoropropane caused convulsions at 7.5 +/- 0.7 atm (mean +/- SD). Convulsions also were produced by perfluorocyclobutane (0.976 +/- 0.002 atm), 1,2-dichlorotetrafluoroethane (0.358 +/- 0.011 atm), 2,3-dichlorooctafluorobutane (0.085 +/- 0.007 atm), 1,2-dichlorohexafluorocyclobutane (0.055 +/- 0.007 atm), and flurothyl (0.00156 +/- 0.00039 atm). Of these, 1,2-dichlorotetrafluoroethane is a transitional compound, the remainder being nonanesthetics. The combination of flurothyl plus 1,2-dichlorohexafluorocyclobutane gave evidence of antagonism (a 17% +/- 21% deviation from additivity; P < 0.05), whereas the combination of 1,2-dichlorotetrafluoroethane plus 2,3-dichlorooctafluorobutane gave evidence of synergy (a -13% +/- 8% deviation from additivity; P < 0.05). The combinations of perfluoropropane plus perfluorocyclobutane (-4% +/- 15%), and perfluoropropane plus 1,2-dichlorohexafluorocyclobutane (-1% +/- 26%) did not produce results that deviated significantly from additivity. We conclude that pairs of these compounds either produce convulsions in an additive manner, a finding consistent with (but not proving) a common mode of action; or deviate modestly from additivity, a finding suggesting that at least a portion of the mechanistic basis for convulsions might differ, particularly for flurothyl plus other nonanesthetics, or for the combination of non-anesthetics and transitional compounds.
authors.affiliation: Department of Anesthesia, S-455, University of California, San Francisco 94143-0464, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.forename: M J
authors.initials: MJ
authors.lastname: Laster
authors.forename: D
authors.initials: D
authors.lastname: Gong
authors.forename: P
authors.initials: P
authors.lastname: Ionescu
authors.forename: D D
authors.initials: DD
authors.lastname: Koblin
authors.forename: J
authors.initials: J
authors.lastname: Sonner
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: M J
authors.initials: MJ
authors.lastname: Halsey
mesh_terms: D000818:Animals; D017402:Chlorofluorocarbons / Q000494:pharmacology; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane / Q000494:pharmacology; D003292:Convulsants; D003503:Cyclobutanes / Q000494:pharmacology; D004347:Drug Interactions; D005466:Fluorocarbons / Q000494:pharmacology; D005481:Flurothyl / Q000494:pharmacology; D005740:Gases; D006371:Helium / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D003292:Convulsants; D003503:Cyclobutanes; D005466:Fluorocarbons; D005740:Gases; D006371:Helium; C100837:2,3-dichlorooctafluorobutane; C090640:1,2-dichloro-1,2,3,3,4,4-hexafluorocyclobutane; C007783:Freon 114; D005481:Flurothyl; C042852:perflutren