Ecotoxicology of narcosis: stereoselectivity and potential target sites.

Abstract

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.

• Authors: Heinrich Sandermann
• Journal: Chemosphere (Chemosphere) Vol. 72 Issue 9 Pg. 1256-9 (Jul 2008) ISSN: 0045-6535 [Print] England
• PMID: 18561982 (Publication Type: Journal Article)

Chemical References

• Anesthetics, Intravenous
• Environmental Pollutants
• Propofol

Topics

• Anesthetics, Intravenous (chemistry, toxicity)
• Animals
• Chemical Phenomena
• Chemistry, Physical
• Environmental Pollutants (chemistry, toxicity)
• Larva
• Propofol (chemistry, toxicity)
• Rana temporaria
• Stereoisomerism
• Structure-Activity Relationship
• Stupor (chemically induced)
• Xenopus laevis