Detection and Characterization of Endogenous Benzodiazepine Activity in Both Animal Models and Humans with Hepatic Encephalopathy
The search for endogenous ligands for central nervous system benzodiazepine(BZ) receptors and the definition of the fundamental mechanism responsible for the mediation of hepatic encephalopathy(HE) have had parallel courses in futility until very recently.1 These apparently disparate fields of interest have converged because of experimental observations made in animal models of HE. The catalyst for this joining of forces was the development of BZ receptor antagonists. These drugs e.g. Ro 15–1788 (Flumazenil) and CGS-8216 largely devoid of effect in controls reverse the sedative effects of synthetic agonist BZ compounds. Administration of these agents to animal models of HE resulted in considerable amelioration in the manifestations of HE2,3 which has been corroborated to some degree in isolated human reports. While the response in HE was not as complete as that seen with administration of the drug to controls treated with agonist BZ drugs it was of sufficient magnitude to suggest a significant neurological event was taking place which required further study.
KeywordsHepatic Encephalopathy Fulminant Hepatic Failure Radioreceptor Assay Diazepam Binding Inhibitor Beta Carboline
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