The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat.

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.

• Authors: D K Bosman, C A van den Buijs, J G de Haan, M A Maas, R A Chamuleau
• Journal: Gastroenterology (Gastroenterology) Vol. 101 Issue 3 Pg. 772-81 (Sep 1991) ISSN: 0016-5085 [Print] United States
• PMID: 1650320 (Publication Type: Journal Article)

Chemical References

• Azides
• Benzodiazepinones
• Receptors, GABA-A
• Benzodiazepines
• Flumazenil
• Ro 15-3505
• Ro 15-4513

Topics

• Animals
• Azides (therapeutic use)
• Benzodiazepines (antagonists & inhibitors, therapeutic use)
• Benzodiazepinones (therapeutic use)
• Electroencephalography
• Evoked Potentials, Visual (drug effects)
• Flumazenil (therapeutic use)
• Hepatic Encephalopathy (drug therapy)
• Male
• Rats
• Rats, Inbred Strains
• Receptors, GABA-A (drug effects)