Abstract:
:Two benzodiazepine-receptor partial inverse agonists (Ro 15-4513, Ro 15-3505) and one benzodiazepine-receptor antagonist (flumazenil) were administered to rats with hepatic encephalopathy due to acute liver ischemia. Significant improvement (P less than 0.002) of both the clinical grade of hepatic encephalopathy and the electroencephalographic abnormalities was observed after administration of the benzodiazepine-receptor partial inverse agonists: comatose rats with no spontaneous righting reflex regained consciousness immediately after injection of the drug. Only slight improvement in clinical hepatic encephalopathy grade was seen after administration of 25 mg/kg of flumazenil. The present data strongly support a role of increased gamma-aminobutyric acid-ergic tone in the pathogenesis of acute hepatic encephalopathy and provide a rationale for trials of benzodiazepine-receptor partial inverse agonists to restore consciousness in hepatic encephalopathy in humans in the near future.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Bosman DK,van den Buijs CA,de Haan JG,Maas MA,Chamuleau RAdoi
10.1016/0016-5085(91)90538-vkeywords:
subject
Has Abstractpub_date
1991-09-01 00:00:00pages
772-81issue
3eissn
0016-5085issn
1528-0012pii
0016-5085(91)90538-Vjournal_volume
101pub_type
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