On the Disulfiram-Like Effect of Coprine, the Pharmacologically Active Principle of Coprinus atramentarius

Abstract

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 increased 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 i.p. injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood-pressure. This effect was accompanied by tachycardia only in animals treated with coprine. Apparently, 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.