To obtain drugs which are more selective at benzodiazepine (BZD) receptors, design and synthesis of functionally selective ligands for BZD receptors is the current strategy of our pharmaceutical chemistry department. The affinity of newly synthesized ligands is assessed by radioligand receptor binding assays. Based on our previous studies, 2-phenyl-5-oxo-7-methyl-1,3, 4-oxadiazolo[a,2,3]-pyrimi...

Midazolam is a short-acting agent used for preoperative and conscious sedation. Despite a relatively short half-life, midazolam sedation contributes to postoperative sedation, delays in discharge, and increased costs. Administration of flumazenil, a benzodiazepine antagonist, can reverse the centrally mediated effects of midazolam and facilitate patient recovery and discharge, thereby reducing ...

BACKGROUND Preferred models for the pharmacokinetic analysis of [11C]flumazenil human studies have been previously established. However, direct translation of these models and settings to animal studies might be sub-optimal. Therefore, this study evaluates pharmacokinetic models for the quantification of [11C]flumazenil binding in the rat brain. Dynamic (60 min) [11C]flumazenil brain PET scans ...

Using [11C]flumazenil-PET and statistical parametric mapping (SPM), we have shown recently that regions of increased and decreased benzodiazepine receptor density may be seen in patients with localization-related epilepsy due to malformations of cortical development. These abnormalities were seen both within and beyond lesions visually apparent on high-resolution MRI. We have also shown, using ...

OBJECTIVES Increasing evidence suggests that metabolic changes predate neuronal death in Huntington's disease and emission tomography methods (PET and SPECT) have shown changes in glucose consumption and receptor function in early and possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor complex (BZR) is expressed on virtually all cerebral neurons BZR density images ...

To obtain drugs which are more selective at benzodiazepine (BZD) receptors, design and synthesis of functionally selective ligands for BZD receptors is the current strategy of our pharmaceutical chemistry department. The affinity of newly synthesized ligands is assessed by radioligand receptor binding assays. Based on our previous studies, 2-phenyl-5-oxo-7-methyl-1,3,4-oxadiazolo[a,2,3]-pyrimid...

BACKGROUND/AIMS To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volu...

The efficacy and safety of flumazenil in reversing midazolam-induced paradoxical reaction in a child suffering from paroxysmal supraventricular tachycardia (PSVT) and undergoing radiofrequency ablation procedure has not been described before. We report a boy who had suffered for years from poorly controlled PSVT because of noncompliance to medications and was being sedated by midazolam and morp...

The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by t...