Stereoselective Effects of Etomidate Optical Isomers on Gamma‐aminobutyric Acid Type A Receptors and Animals

@article{Tomlin1998StereoselectiveEO,
  title={Stereoselective Effects of Etomidate Optical Isomers on Gamma‐aminobutyric Acid Type A Receptors and Animals},
  author={Sarah L. Tomlin and Andrew Jenkins and William Robert Lieb and Nicholas P. Franks},
  journal={Anesthesiology},
  year={1998},
  volume={88},
  pages={708–717}
}
Background The intravenous anesthetic etomidate is optically active and exists in two mirror‐image enantiomeric forms. However, although the R(+) isomer is used as a clinical anesthetic, quantitative information on the relative potencies of the R(+) and S(‐) isomers is lacking. These data could be used to test the relevance of putative molecular targets. Methods The anesthetic concentrations for a half‐maximal effect (EC50) needed to induce a loss of righting reflex in tadpoles (Rana temporaria… 
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Preparation of barbiturate optical isomers and their effects on GABA(A) receptors.
TLDR
The rank order and degree of stereoselectivity that are observed for the enantiomers of hexobarbital, pentobar bital, and thiopental acting on the gamma-aminobutyric acid type A receptor are entirely consistent with this receptor playing a central role in the anesthetic actions of barbiturates.
The in vitro and in vivo enantioselectivity of etomidate implicates the GABAA receptor in general anaesthesia
Effects of thiopental and its optical isomers on nicotinic acetylcholine receptors.
TLDR
Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia.
Identification of Anesthetic Binding Sites on Human Serum Albumin Using a Novel Etomidate Photolabel*
TLDR
A novel analog of the general anesthetic etomidate in which the ethoxy group has been replaced by an azide group is synthesized, and which can be used as a photolabel to identify etomidates binding sites, and may prove to be a useful new photolab to identify anesthetic binding sites on the GABAA receptor or other putative targets.
Differential Potency of 2,6-Dimethylcyclohexanol Isomers for Positive Modulation of GABAA Receptor Currents
TLDR
The stereochemical configuration within the dimethylcyclohexanols is an important molecular feature in conferring positive modulation of GABAA receptor activity and for binding to the receptor, a consideration that needs to be taken into account when designing novel anesthetics with enhanced therapeutic indices.
Ecotoxicology of narcosis: stereoselectivity and potential target sites.
Lack of enantiomeric specificity in the effects of anesthetic steroids on lipid bilayers.
Cyclohexanol analogues are positive modulators of GABA(A) receptor currents and act as general anaesthetics in vivo.
Analogues of Etomidate: Modifications around Etomidate’s Chiral Carbon and the Impact on In Vitro and In Vivo Pharmacology
TLDR
Changing etomidate’s chiral center may be used as part of a strategy to design analogues with more desirable adrenocortical activities and/or subunit selectivities.
Etomidate and other non-barbiturates.
TLDR
The most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids are summarized.
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