Diazepam- and chlordiazepoxide-mediated increases in erythrocyte aldehyde dehydrogenase activity and its possible implications.
Erythrocyte ALDH activity was assayed in alcoholic (n = 70) and nonalcoholic (n = 40) subjects. In general, alcoholics without any prior medications (n = 57) were found to have a decreased ALDH activity (mean +/- SD: 3.38 +/- 1.7 mU; p less than 0.001) as compared to control group (5.10 +/- 1.57 mU). However, a group of alcoholics who were detoxified with benzodiazepines (n = 13) prior to blood collection for enzyme assay were found to have higher ALDH activity (4.92 +/- 2.46 mU; p less than 0.05) as compared to alcoholics who were not detoxified. In vitro experiments demonstrated that both diazepam (DZM) and chlordiazepoxide (CDP) could activate the ALDH. The magnitude of enzyme activation by DZM and CDP appear to correlate with their relative potency of tranquilizing effect. Further, the observed ability of DZM to reverse the inhibition of ALDH mediated by disulfiram may explain the biochemical basis of the reported ability of benzodiazepines (BDZ) to reduce the intensity of disulfiram ethanol reaction (DER).
Murthy
P
P
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Guru
S C
SC
Shetty
K T
KT
Ray
R
R
Channabasavanna
S M
SM
D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000188:drug therapy; D000444:Aldehyde Dehydrogenase / Q000097:blood*; D001569:Benzodiazepines / Q000627:therapeutic use; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D012016:Reference Values
D001569:Benzodiazepines; D002707:Chlordiazepoxide; D000444:Aldehyde Dehydrogenase; D003975:Diazepam