title: Structure-activity relationship of etomidate derivatives at the GABA(A) receptor: Comparison with binding to 11beta-hydroxylase.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University of Vienna, Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Atucha
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hammerschmidt
authors.forename: Ilse
authors.initials: I
authors.lastname: Zolle
authors.forename: Werner
authors.initials: W
authors.lastname: Sieghart
authors.forename: Michael L
authors.initials: ML
authors.lastname: Berger
mesh_terms: D018686:Anesthetics, Intravenous / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005045:Etomidate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008297:Male; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry*; D013237:Stereoisomerism; D013252:Steroid 11-beta-Hydroxylase / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D013252:Steroid 11-beta-Hydroxylase; D005045:Etomidate