A benzodiazepine antagonist does not alter the course of hepatic encephalopathy or neural gamma-aminobutyric acid (GABA) binding.
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 gamma-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.
Zieve
L
L
VA Medical Center, Minneapolis, Minnesota.
Ferenci
P
P
Rzepczynski
D
D
Ebner
J
J
Zimmermann
C
C
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D006499:Hepatic Artery / Q000502:physiology*; D006501:Hepatic Encephalopathy / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D008102:Liver Circulation; D008297:Male; D011167:Portacaval Shunt, Surgical; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011720:Pyrazoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D003975:Diazepam