Elevated Brain Concentrations of 1,4-Benzodiazepines in Fulminant Hepatic Failure

Increased activity of the γ-aminobutyric acid [GABA] neurotransmitter (GABA-ergic) system may have a fundamental role in the pathogenesis of hepatic encephalopathy, 1 , 2 a complex neuropsychiatrie disorder that complicates acute or chronic liver failure. 3 Electrophysiologic, 4 5 6 neurochemical, 7 8 9 10 11 12 and behaviora 15 , 6 , 13 evidence from several animal models of hepatic encephalopathy due to fulminant hepatic failure indicates that a major factor enhancing GABA-ergic tone is an elevation of the concentrations of substances that inhibit the binding of a Radio-labeled imidazobenzodiazepine ([ 3 H]flumazenil) to its receptors (benzodiazepine-receptor ligands) that have agonist (i.e., diazepam-like) properties. The ability of benzodiazepines to augment GABA-ergic tone through a receptor-mediated mechanism is well . . .