On the disulfiram-like effect of coprine, the pharmacologically active principle of Coprinus atramentarius.
Coprine or disulfiram was given to rats in various doses at various time intervals before the administration of 2 g/kg ethanol. The ratio acetaldehyde/ethanol in the alveolar air was measured by gas chromatography and was taken as an index of the aldehyde dehydrogenase (ALDH) activity. The activity of dopamine beta-hydroxylase (DBH) was estimated in the same animals by measuring the amount of 14C-octopamine formed from 14C-tyramine in the heart. Coprine and disulfiram both caused an increase in the acetylaldehyde/ethanol ratio, coprine being more potent than disulfiram. Disulfiram, but not coprine, reduced the net yield of 14C-octopamine. In rats pretreated with either coprine or disulfiram, blood-pressure and heart-rate were recorded before and after intraperitoneal injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood-pressure. However, this effect was accompanied by tachycardia only in animals treated with coprine. It is concluded that coprine like disulfiram inhibits ALDH, but only disulfiram causes an additional inhibition of DBH. This difference may account for differences in the cardiovascular response to ethanol.
D000363:Agaricales; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003302:Coprinus; D003521:Cyclopropanes / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009655:Octopamine / Q000378:metabolism; D051381:Rats; D014439:Tyramine / Q000378:metabolism
D000447:Aldehydes; D003521:Cyclopropanes; D009655:Octopamine; D000431:Ethanol; D004299:Dopamine beta-Hydroxylase; D000445:Aldehyde Oxidoreductases; D004221:Disulfiram; D014439:Tyramine