Effects of Ethyleneglycol Dinitrate and Related Compounds on Ethanol Preference and Ethanol Metabolism

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Abstract
Ethanol preference in rats (ALKO strains) was studied by injecting ethyleneglycol dinitrate, glyceryl trinitrate, propyleneglycol dinitrate and ethyleneglycol mononitrate. Their effects on ethanol metabolism and on the activities of liver alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (AldDH) were also examined. All four compounds caused a marked decrease in ethanol preference. When administered 30 minutes before the injection of ethanol, all four drugs significantly delayed the disappearance of ethanol and acetaldehyde from the blood. With 150 mg/kg b.wt. of ethyleneglycol dinitrate, the blood acetaldehyde level reached 770 nmol/ml one hour after ethanol (2 g/kg b.wt.) injection. This contrasted with 30 nmol/ml for the control. Similar results were obtained with the other compounds. 3 hours after the administration of 150 mg/kg of nitrate, the liver ADH activities were inhibited by 21‐46% and the liver Ald DH activities by 32‐60%. These findings suggest that the decrease in ethanol preference and the inhibition of ethanol and acetaldehyde elimination are closely related to the decrease in liver ADH and AldDH activities in the presence of these four organic nitrates.