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Abstract-The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment.Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreat ment with antibiotics.A similar time course change in the effect was obtained when disulfiram was administered.The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram like effect was followed by a disappearance of the drugs. Secondly, the concen tration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration.Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.

Abstract-Liver microsomal vitamin K epoxide reductase activity was determined by measuring the formation of menaquinone-4 from the substrate menaquinone-4 2,3-epoxide.The enzyme was active when dithiothreitol (DTT) was used as a reducing agent, and the activity increased gradually with increasing concentrations of DTT. Glutathione and cysteine also functioned as reductants, but these physio logical reductants showed less than 15% of the activity detected with 0.5 mM DTT.