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A benzodiazepine antagonist does not alter the course of hepatic encephalopathy or neural γ-aminobutyric acid (GABA) binding

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Abstract

The progressive course of hepatic encephalopathy developing in rats after massive hepatic ischemia due to hepatic artery ligation within 48 hr of a portacaval shunt was not altered by the injection of a benzodiazepine antagonist, CGS 8216, in a dose that was sufficient to reverse diazepam-induced coma quickly. The onset of hepatic coma was shortened 20 to 25% by the antagonist, rather than being delayed, as would be expected if hepatic coma were due to a γ-aminobutyric acid (GABA)-ergic effect. The neural binding of GABA by brains from rats in deep hepatic coma was unaffected by the injection of the benzodiazepine antagonist.

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References

  • Baraldi, M., and Zeneroli, M. L. (1982). Experimental hepatic encephalopathy: Changes in γ-aminobutyric acid.Science 216: 427–431.

    Google Scholar 

  • Baraldi, M., Zeneroli, M. L., Ventura, E.,et al. (1984a). Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: Reversal by a benzodiazepine antagonist.Clin. Sci. 67: 167–175.

    Google Scholar 

  • Baraldi, M., Zeneroli, M. L., Ventura, E.,et al. (1984b). Port-systemic encephalopathy in dogs: Changes in brain GABA receptors and neurochemial correlates. In Kleinberger, G., Ferenci, P., Riederer, P., and Thaler, H. (eds.),Advances in Hepatic Encephalopathy and Urea Cycle Diseases, S. Karger, Basel, pp. 353–359.

    Google Scholar 

  • Baraldi, M., Pinelli, G., Ricci, P., and Zeneroli, M. L. (1984c). Toxins in hepatic encephalopathy: The role of the synergistic effect of ammonia, mercaptans and short chain fatty acids.Arch. Toxicol. Suppl. 7: 103–105.

    Google Scholar 

  • Bassett, M. L., Mullen, K. D., Skolnick, P., and Jones, E. A. (1985). GABA and benzodiazepine receptor antagonists ameliorate hepatic encephalopathy in a rabbit model of fulminant hepatic failure.Hepatology 5: 1032.

    Google Scholar 

  • Ferenci, P., Pappas, S. C., Munson, P. J., Henson, K., and Jones, E. A. (1984). Changes in status of neurotransmitter receptors in a rabbit model of hepatic encephalopathy.Hepatology 4: 186–191.

    Google Scholar 

  • Ferenci, P., Zieve, L., Ebner, J., Zimmermann, Ch., and Rzepczynski, D. (1986a). Postsynaptic neural membrane affinity for GABA and receptor density are unaltered in hepatic coma following portacaval shunt and hepatic artery ligation.Hepatology 6: 1143.

    Google Scholar 

  • Ferenci, P., Zimmermann, Ch., and Ebner, J. (1986b). Thioacetamide acute liver failure in the rat—a suitable model for hepatic encephalopathy?J. Hepatol. 3 (Suppl. 1): 121.

    Google Scholar 

  • Ferenci, P., Zieve, L., Ebner, J., Zimmermann, Ch., and Rzepczynski, D. (1987). Postsynaptic γ-aminobutyric acid receptors in hepatic coma following portacaval shunt and hepatic artery ligation in the rat.Metab. Brain Dis. 2: 195–200.

    Google Scholar 

  • Maddison, J. E., Dodd, P. R., Johnston, G. A. R., and Farrell, G. C. (1987). Brain GABA receptor binding is normal in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma GABA-like activity.Gastroenterology 92 (in press).

  • Rzepczynski, D., Zieve, L., Lindblad, S., and LaFontaine, D. (1986). In vivo studies of GABAergic effects in experimental hepatic encephalopathy.Hepatology 6: 902–905.

    Google Scholar 

  • Schafer, D. F., Fowler, J. M., Munson, J. P., Thakur, A. K., Waggoner, J. G., and Jones, E. A. (1983). Gamma-amino-butyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure.J. Lab. Clin. Med. 102: 870–880.

    Google Scholar 

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Zieve, L., Ferenci, P., Rzepczynski, D. et al. A benzodiazepine antagonist does not alter the course of hepatic encephalopathy or neural γ-aminobutyric acid (GABA) binding. Metabolic Brain Disease 2, 201–205 (1987). https://doi.org/10.1007/BF00999611

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  • DOI: https://doi.org/10.1007/BF00999611

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