Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy

Journal Article · Sun Jul 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.14.5263· OSTI ID:6249837

Basile, A S; Pannell, L; Jaouni, T; Gammal, S H; Fales, H M; Jones, E A; Skolnick, P ^[1]

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1. National Institutes of Health, Bethesda, MD (USA)

Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans.

• OSTI ID: 6249837
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:14; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMISTRY
BIOLOGICAL MODELS
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
CHROMATOGRAPHY
DIAZO COMPOUNDS
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
DRUGS
GLANDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
LIGANDS
LIVER
MASS SPECTROSCOPY
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOCHROMATOGRAPHY
RADIORECEPTOR ASSAY
SEPARATION PROCESSES
SPECTROSCOPY
TRACER TECHNIQUES
TRITIUM COMPOUNDS