A Comparative Study on the Effects of Disulfiram, Cyanamide and 1‐Aminocyclopropanol on the Acetaldehyde Metabolism in Rats

Abstract

1-aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2-24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low-K_m ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high-K_m ALDH only in vivo, whereas in vitro, the high-K_m ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low-K_m enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram-ethanol reaction are discussed.