INHIBITING ACTION OF n-BUTYRALDOXIME ON ETHANOL METABOLISM AND ON NATURAL ETHANOL PREFERENCE OF C57BL MICE

¹ Department of Pharmacology, Medical Research Laboratories, Pfizer Inc., Groton, Connecticut

Simultaneous consumption of butyraldoxime and ethanol induced a strong and protracted decrease in ethanol preference in C57BL mice, a strain with natural preference for ethanol solutions. Biochemical studies showed that butyraldoxime is a potent inhibitor of hepatic alcohol dehydrogenase in vitro and in vivo in rodents. Intraperitoneal treatment resulted in decreased activity of liver extracts, delayed disappearance of blood ethanol after an ethanol dose and reduced accumulation of citric acid in kidney elicited by fluoroethanol. The lack of in vitro inhibition of hepatic aldehyde dehydrogenase was confirmed; however, butyraldoxime is a strong inhibitor of aldehyde dehydrogenase in vivo. Intraperitoneal treatment resulted in decreased activity of liver extracts and acetaldehyde accumulation in blood after an ethanol dose. After chronic intake of butyraldoxime in the drinking fluid, mice and rats also showed markedly decreased aldehyde dehydrogenase activity but slightly enhanced alcohol dehydrogenase activity. Subsequent administration of ethanol resulted in the appearance of substantial amounts of acetaldehyde in blood and a slightly slower rate of disappearance of ethanol from blood. These findings suggest that the antialcohol action of butyraldoxime in C57BL mice and in man is probably derived from hepatic aldehyde dehydrogenase blockade which interferes with the metabolism of acetaldehyde derived from ethanol. Analogous effects on ethanol metabolism were also found for several homologous aldoximes.