Effects of the Dopamine-β-hydroxylase Inhibitors FLA-57 and FLA-63 on Ethanol Metabolism and Aldehyde Dehydrogenase Activity in Rats

Abstract: In rats pretreated with the dopamine-β-hydroxylase (DBH)-inhibitors FLA-57 and FLA-63 (60 mg/kg, intraperitoneally, for 4 and 18 hrs), no effects on the blood acetaldehyde level after ethanol administration or on the activity of the low-K_m aldehyde dehydrogenase (ALDH) in the liver were found. FLA-63 but not FLA-57 decreased the rate of ethanol elimination. FLA-63 inhibited the low-K_m enzyme in vitro, but much less than the ALDH-inhibitors disulfiram and cyanamide. FLA-57 caused no inhibition in vitro. The results show that the previously observed suppression of ethanol intake in rats by FLA-57 and FLA-63 was not caused by an acetaldehyde-mediated aversion such as during the disulfiram-ethanol reaction.