MOLECULAR-STRUCTURE AND STEREOELECTRONIC PROPERTIES OF SARMAZENIL - AWEAK INVERSE AGONIST AT THE OMEGA-MODULATORY SITES (BENZODIAZEPINE RECEPTORS) - COMPARISON WITH BRETAZENIL AND FLUMAZENIL

X-ray diffraction and ab initio MO theoretical calculations were used in order to investigate the structural and electronic properties of sa rmazenil, a weak inverse agonist at the omega modulatory sites (benzod iazepine receptors. This compound was compared to bretazenil, a partia l agonist, and to the antagonist flumazenil on the basis of structural and electronic data. The conformational and theoretical properties (i nteratomic pi overlap populations, molecular electrostatic potential ( MEP), the topology of frontier orbitals, and proton affinity) of these three imidazobenzodiazepinones were determined in order to analyse th e stereoelectronic properties in relation with their distinct intrinsi c efficacies at the omega modulatory sites. (C) 1998 Elsevier Science Ltd. All rights reserved.