Are convulsant gases also anesthetics?
This study investigated whether the convulsant gas flurothyl deviates from the correlation between anesthetic potency and lipid solubility. Flurothyl (CF3CH2OCH2CF3) produced convulsions in 50% of mice at 0.122 +/- 0.006% atm. Mice often convulsed repeatedly after exposure to flurothyl, the maximum number of convulsions occurring when the concentration was 0.24% atm. Concentrations greater than 0.6% atm produced convulsions immediately after addition of flurothyl, but rarely at later times. An ED50 value for loss of the righting reflex was obtained when the concentration was 1.22 +/- 0.19% atm. The oil/gas partition coefficient was found to be 46.9 for flurothyl at 37 C. The product of righting-reflex ED50 and oil/gas partition coefficient (0.0122 atm x 46.9 = 0.57 atm) is similar to that found for conventional anaesthetics in mice. Therefore, flurothyl does not deviate from the correlation of anesthetic potency and lipid solubility. It was also found that 0.3 to 0.8% atm flurothyl increased isoflurane MAC in dogs, but that 3 to 4% atm flurothyl decreased it. The increase of isoflurane requirement at lower concentrations of flurothyl suggests that anesthetics with a potential to cause convulsions may partly antagonize their own anesthetic effect. The decrease in isoflurane MAC in dogs at higher concentrations of flurothyl also implies that this compound has an anesthetic effect. A structural isomer of flurothyl, iso-Indoklon [(CSF3)2CHOCH3], was only anesthetic and did not have convulsant properties. Its MAC in dogs was 4.60 +/- 0.45% atm, and its righting-reflex ED50 in mice was 2.65 +/- 0.13% atm. The product of iso-Indoklon MAC in dogs and its oil/gas partition coefficient (27.0) was 1.24 atm, and the product of iso-Indoklon righting-reflex ED50 in mice and oil/gas partition coefficient was 0.72 atm. These values are close to those found for conventional anesthetic agents in dogs and mice; thus iso-Indoklon also does not deviate from the correlation between anesthetic potency and lipid solubilities.
D000769:Anesthesia, Inhalation; D000777:Anesthetics; D000818:Animals; D003292:Convulsants; D004285:Dogs; D005260:Female; D005481:Flurothyl / Q000494:pharmacology*; D007530:Isoflurane / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D005466:Fluorocarbons
D000777:Anesthetics; D003292:Convulsants; D005481:Flurothyl; D007530:Isoflurane; C030560:iso-Indoklon; D005466:Fluorocarbons