EFFECTS OF BENZODIAZEPINES ON ALDEHYDE DEHYDROGENASE-ACTIVITY

The reported ability of benzodiazepines to increase human erythrocyte aldehyde dehydrogenase (ALDH) activity and reverse the disulfiram-indu ced inhibition of ALDH was reexamined. When ALDH activity assays were carried out spectrophotometrically on a hemoglobin-free lysate of huma n erythrocytes with propionaldehyde as substrate, addition of diazepam (10 mu mol/l) did not affect the enzyme activity. When assays were ca rried out on intact or hemolysed erythrocytes using high performance l iquid chromatographic technique with 3,4-dihydroxyphenylacetaldehyde a s substrate, no significant increase in erythrocyte ALDH activity was found in the presence of chlordiazepoxide, oxazepam, diazepam, or desm ethyldiazepam in the concentration range 1-20 mu mol/l. Rather, a sign ificant decrease (about 50%) in activity was obtained when lysed cells were incubated with 20 mu mol/l chlordiazepoxide. Diazepam inhibited the rat liver mitochondrial low K(m)ALDH activity by about 50%. Disulf iram 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 o f disulfiram reduced when diazepam was added prior to disulfiram. In a n alcoholic subject who was followed during onset of disulfiram (Antab use) therapy, the concurrent use of diazepam did not prevent a rapid d ecline in blood ALDH activity. The present results suggest that benzod iazepines do not increase ALDH activity in vitro, nor interfere with t he inhibition of ALDH by disulfiram.