Structure-activity relationship of etomidate derivatives at the GABA(A) receptor: Comparison with binding to 11beta-hydroxylase

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4284-7. doi: 10.1016/j.bmcl.2009.05.065. Epub 2009 May 24.

Abstract

At the GABA(A) receptor, low concentrations of etomidate potentiate the inhibitory effect of GABA on specific binding of the closed channel ligand [(3)H]ethynylpropylbicycloorthobenzoate ([(3)H]EBOB). Here, we present SARs for etomidate and structurally related compounds inducing this effect. In the absence of GABA, similar SARs, but 14-20 times weaker potencies were observed. We discuss these SARs in comparison to the much higher potencies of these compounds as inhibitors of 11beta-hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / chemical synthesis
  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Binding Sites
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Etomidate / analogs & derivatives*
  • Etomidate / chemical synthesis
  • Etomidate / chemistry
  • Inhibitory Concentration 50
  • Male
  • Models, Chemical
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / chemistry*
  • Stereoisomerism
  • Steroid 11-beta-Hydroxylase / chemistry*
  • Steroid 11-beta-Hydroxylase / metabolism
  • Structure-Activity Relationship

Substances

  • Anesthetics, Intravenous
  • Receptors, GABA-A
  • Steroid 11-beta-Hydroxylase
  • Etomidate