Conformationally constrained anesthetic steroids that modulate GABA(A) receptors.
J Med Chem
; 43(22): 4118-25, 2000 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-11063608
ABSTRACT
Various cyclic ether and other 3 alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar in vitro and in vivo activities to the endogenous 3 alpha-hydroxypregnan-20-ones all had an ether oxygen on the beta-face of the steroid D-ring. These results suggest that for optimal GABA(A) receptor modulation, the hydrogen bond-accepting substituent should be near perpendicular to the plane of the D-ring on the beta-face of the steroid.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de GABA-A
/
Moduladores GABAérgicos
/
Androstanóis
/
Anestésicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article