Effects of inhaled nonimmobilizer, proconvulsant compounds on desflurane minimum alveolar anesthetic concentration in rats.
Anesthetics depress the central nervous system, whereas nonimmobilizers (previously called nonanesthetics) and transitional compounds having the same physical properties (e.g., solubility in lipid) do not produce anesthesia (nonimmobilizers) or are less potent anesthetics than might be predicted from their lipophilicity (transitional compounds). Potential explanations for the absent or decreased anesthetic effect of nonimmobilizer and transitional compounds include the theories that the nonimmobilizers are devoid of anesthetic effect and that transitional compounds have a decreased capacity to produce anesthesia; that the effects of these compounds are not apparent because the concentrations examined are too low; or that anesthesia, or lack thereof, results from a balance between depression and excitation (all nonimmobilizer and transitional compounds produce convulsions). To examine these issues further, we tested the effect of various multiples of the convulsive 50% effective dose (ED50) of three nonimmobilizers and one transitional compound on the minimum alveolar anesthetic concentration (MAC) of desflurane in rats. The nonimmobilizer 2,3-dichlorooctafluorobutane (NI-1), from 0.7 to 1.1 times its convulsive ED50, increased the MAC of desflurane by 14%-27%, but at 1.6 times its convulsive ED50 caused no change in MAC; the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (NI-2) did not change MAC at concentrations up to its convulsant ED50, but it increased MAC by 25% and 36% at 1.3 and 1.7 times its convulsant ED50, respectively. The nonimmobilizer flurothyl (NI-3) decreased the MAC of desflurane by 20% +/- 6% (mean +/- SD) at 0.5 times its convulsant ED50, but it caused no change at higher partial pressures (up to 7.8 times its convulsant ED50), and the transitional compound CF3CCl2-O-CF2Cl (T-1) significantly decreased MAC by 16% +/- 7% at 0.8 times its convulsant ED50, but the 6%-8% decreases in MAC at 0.4 and 1.6 times its convulsant ED50 were not significant. Thus, neither nonimmobilizer nor transitional compounds produced a consistent dose-related effect on the MAC of desflurane, and any changes were small. These results suggest that the excitation produced by transitional compounds or nonimmobilizers does not explain their limited ability or inability to produce anesthesia. The data are consistent with a decreased anesthetic efficacy of transitional compounds and the lack of efficacy of nonimmobilizers.


CONCLUSIONS
Inhaled compounds that do not cause anesthesia (nonimmobilizers) are used to test theories of anesthetic action. Their use presumes that a trivial explanation, such as cancelling stimulatory and depressant effects, does not explain the absence of anesthesia. The present results argue against such an explanation.
Fang
Z
Z
Department of Anesthesia, University of California, San Francisco 94143-0464, USA.
Laster
M J
MJ
Ionescu
P
P
Koblin
D D
DD
Sonner
J
J
Eger
E I
EI
Halsey
M J
MJ
D000777:Anesthetics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D017402:Chlorofluorocarbons / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D000077335:Desflurane; D004347:Drug Interactions; D005481:Flurothyl / Q000494:pharmacology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000777:Anesthetics; D018685:Anesthetics, Inhalation; D017402:Chlorofluorocarbons; D003292:Convulsants; D003503:Cyclobutanes; C100837:2,3-dichlorooctafluorobutane; C090640:1,2-dichloro-1,2,3,3,4,4-hexafluorocyclobutane; D005481:Flurothyl; D000077335:Desflurane; D007530:Isoflurane