The effect of cephalosporin antibiotics on alcohol metabolism: a review.
A review is made of the pharmacological, biochemical and chemical aspects of the unpleasant 'Antabuse-like' reaction that may be induced in drinkers of alcohol by pre-treatment with certain beta-lactam antibiotics with a 1-methyltetrazole-5-thiol sidechain (such as moxalactam, cefamandole and cefoperazone). The symptoms are due to abnormally elevated blood acetaldehyde levels consequent upon the inactivation of hepatic aldehyde dehydrogenase. There is very little direct effect of the antibiotics on this enzyme and therefore it is concluded that a reactive metabolite of the antibiotics' essential sidechain is responsible for the reaction. A likely candidate for this active species is either the symmetrical disulphide 5,5'-dithiobis(1-methyltetrazole) formed by oxidation of 1-methyltetrazole-5-thiol, or the related mixed disulphide, methyl 5-(1-methyltetrazolyl) disulphide. The first of these is a potent inactivator of cytoplasmic aldehyde dehydrogenase only, the second affects both cytoplasmic and mitochondrial isoenzymes. 1-Methyltetrazole-5-thiol or derivatives have the potential to be used therapeutically as 'anti-alcohol' compounds in the same way as disulfiram (Antabuse) or calcium cyanamide.
D000079:Acetaldehyde / Q000097:blood; D000437:Alcoholism / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D002435:Cefamandole / Q000009:adverse effects; D002438:Cefoperazone / Q000009:adverse effects; D002511:Cephalosporins / Q000009:adverse effects*; D055598:Chemical Phenomena; D002621:Chemistry; D000431:Ethanol / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D009070:Moxalactam / Q000009:adverse effects; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D000431:Ethanol; D002435:Cefamandole; D002438:Cefoperazone; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D009070:Moxalactam