The role of endogenous benzodiazepines in hepatic encephalopathy: animal studies.

Hepatic encephalopathy (HE) resembles encephalopathies induced by drugs, including benzodiazepines (BZs), that potentiate GABAergic neurotransmission. Neurons from animals with HE show increased sensitivity to BZ and GABA receptor agonists. Moreover, these neurons are excited by BZ receptor antagonists at concentration that do not affect control neurons. In addition, elevated levels of 1,4-BZs, including diazepam and N-desmethyldiazepem, have been found in the brains of animals with HE. Furthermore, behavioral and electrophysiologic ameliorations of HE have been induced in animals by BZ receptor antagonists. These findings suggest that endogenous BZs contribute to the manifestations of HE by augmenting GABAergic neurotransmission.