Ecotoxicology of narcosis: Stereoselectivity and potential target sites

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• 作者：Heinrich S ; ermann
• 关键词：Tadpole narcosis ; Stereoselectivity ; Etomidate ; Propofol ; GABA_A channel ; Lipid/protein interface
• 刊名：Chemosphere
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：72
• 期：9
• 页码：1256-1259
• 全文大小：223 K

文摘

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.