Effects of benzodiazepines on aldehyde dehydrogenase activity.
The reported ability of benzodiazepines to increase human erythrocyte aldehyde dehydrogenase (ALDH) activity and reverse the disulfiram-induced inhibition of ALDH was reexamined. When ALDH activity assays were carried out spectrophotometrically on a hemoglobin-free lysate of human erythrocytes with propionaldehyde as substrate, addition of diazepam (10 mumol/l) did not affect the enzyme activity. When assays were carried out on intact or hemolysed erythrocytes using high performance liquid chromatographic technique with 3,4-dihydroxyphenylacetaldehyde as substrate, no significant increase in erythrocyte ALDH activity was found in the presence of chlordiazepoxide, oxazepam, diazepam, or desmethyldiazepam in the concentration range 1-20 mumol/l. Rather, a significant decrease (about 50%) in activity was obtained when lysed cells were incubated with 20 mumol/l chlordiazepoxide. Diazepam inhibited the rat liver mitochondrial low Km ALDH activity by about 50%. Disulfiram inhibited the ALDH activity almost completely in assays on human erythrocyte or rat liver mitochondrial ALDH. The ALDH activity was not regained by the subsequent addition of diazepam, nor was the effect of disulfiram reduced when diazepam was added prior to disulfiram. In an alcoholic subject who was followed during onset of disulfiram (Antabuse) therapy, the concurrent use of diazepam did not prevent a rapid decline in blood ALDH activity. The present results suggest that benzodiazepines do not increase ALDH activity in vitro, nor interfere with the inhibition of ALDH by disulfiram.
Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden.
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Helander
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Burénius
D000328:Adult; D000427:Alcohol Deterrents / Q000494:pharmacology / Q000627:therapeutic use; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D004221:Disulfiram / Q000494:pharmacology / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats
D000427:Alcohol Deterrents; D015415:Biomarkers; D001569:Benzodiazepines; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram