SUPERSENSITIVITY OF GABA-A RECEPTORS IN HEPATIC-ENCEPHALOPATHY

During the past decade a new approach to pathogenetic, studies of hepatic encephalopathy has been undertaken to identify the neurochemical alterations which characterize the syndrome. Using animal models of hepatic encephalopathy electrophysiological, behavioral, pharmacological and biochem evidence were provided of an increased functional activity of the GABA-A receptors, including the Benzodiazepine site. These demonstrations seem to explain the increased sensitivity of patients with acute or chronic liver disease to sedative administration. The described increased tone of the GABAergic receptor complex seems to play a key role in the generalized depression of the central nervous system which characterizes hepatic encephalopathy, but other factors seem to contribute to the neuronal derangement present in this syndrome leading to an imbalance between inhibitory and excitatory receptor systems in the brain. Based on these findings a new symptomatic treatment with antibenzodazepine compounds which seem temporarely to counteract the symptoms of hepatic encephalopathy, was introduced. © 1990 Plenum Publishing Corporation.