Ecotoxicology of narcosis: stereoselectivity and potential target sites.
The stereoselectivity of certain anesthetics is currently thought to be inconsistent with lipid theories of narcosis. The EC50-values of etomidate enantiomers for tadpole narcosis are now examined as a function of octanol/water partition coefficients, and enhancement factors for predicted over experimental EC50 values are determined from a calibration curve for non-selective narcosis. The unfavored S-(-)-enantiomers of etomidate and two analogues surprisingly still fulfill the Meyer-Overton rule. The R+-enantiomers of etomidate and four structural analogues are up to 34-fold more active than expected. The non-chiral anesthetic, propofol, is 8-fold more active than expected. It is concluded that there may be two pathways to tadpole narcosis: enhanced narcosis involving specific receptor binding sites and non-selective narcosis corresponding to the Meyer-Overton rule and operating on the lipid/protein interface.
Sandermann
Heinrich
H
ecotox.freiburg, Schubertstr. 1, Freiburg, Germany. heinrich.sandermann@ctp.uni-freiburg.de
D018686:Anesthetics, Intravenous / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004785:Environmental Pollutants / Q000737:chemistry* / Q000633:toxicity*; D007814:Larva; D015742:Propofol / Q000737:chemistry / Q000633:toxicity; D011896:Rana temporaria; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053608:Stupor / Q000139:chemically induced*; D014982:Xenopus laevis
D018686:Anesthetics, Intravenous; D004785:Environmental Pollutants; D015742:Propofol