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Selective antagonists of benzodiazepines
The main properties of a representative of this novel class of specific benzodiazepine antagonists are described, whose unique pharmacological activity is to prevent or abolish in a highly selective manner at the receptor level all the characteristic centrally mediated effects of active Benzodiazepines. Expand
Prolonged sedation due to accumulation of conjugated metabolites of midazolam
Serum concentration monitoring showed high concentrations of conjugated alpha-hydroxymidazolam when concentrations of the unconjugated metabolite and the parent drug were below the therapeutic range, and in-vitro binding studies showed that the affinity of binding to the cerebral benzodiazepine receptor of glucuronidated alpha-Hydroxymidine receptor was only about ten times weaker than that of midazolham. Expand
In vitro and in vivo evaluation of iodine-123-Ro 16-0154: a new imaging agent for SPECT investigations of benzodiazepine receptors.
The purified 123I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations, and its pharmacologic properties were comparable to those of flumazenil. Expand
Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists.
The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1) receptor antagonists is described, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration. Expand
Photoaffinity labeling of benzodiazepine receptors with a partial inverse agonist.
Ro 15-4513: Partial inverse agonism at the BZR and interaction with ethanol
The imidazobenzodiazepinone derivative Ro 15-4513 reverses central nervous depressant effects of diazepam, and, in part, of phenobarbitone and ethanol in mice, rats and cats in behavioural, electrophysiological, and neurochemical paradigms. Expand
The story of flumazenil.
The discovery of flumazenil confirmed the mechanism of action of BZs through specific BZRs and demonstrated the feasibility of obtaining BZR ligands covering a broad spectrum of intrinsic efficacies, from full agonist, partial agonists, antagonists, partial inverse agonists to full inverse agonist. Expand
Synthetic and computer-assisted analysis of the structural requirements for selective, high-affinity ligand binding to diazepam-insensitive benzodiazepine receptors.
3D-QSAR analyses were carried out on ligand affinities at both of these benzodiazepine receptor (BzR) isoforms to determine the structural requirements for both high affinity and selectivity at DI BzR relative to DS, based on the new X-ray crystallographic data. Expand