Effects of dopamine-beta-hydroxylase inhibitors FLA-57 and FLA-63 on ethanol metabolism and aldehyde dehydrogenase activity in rats.
In rats pretreated with the dopamine-beta-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-Km 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-Km 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.
D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D000431:Ethanol / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001381:Azepines; D007093:Imidazoles; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; C015590:4-methyl-1-homopiperazinedithiocarboxylic acid; D000431:Ethanol; D004299:Dopamine beta-Hydroxylase; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase