Molecular Pharmacology, Vol 6, 416-424, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Acetaldehyde Mediation in the Mechanism of Ethanol-Induced Changes in Norepinephrine Metabolism

¹ Department of Pharmacology, The Ohio State University School of Medicine, and Battelle Memorial Institute, Columbus, Ohio 43210
² Metabolic Research Laboratory, Veterans Administration Hospital, Houston, Texas 77031

The role of acetaldehyde in reducing the oxidative pathway and increasing the reductive route for norepinephrine (NE) metabolism was evaluated. Experiments were performed in which ¹⁴C-NE was injected into rats and its metabolic fate in vivo was monitored in the urine. Ethanol administration failed to alter the biochemical disposition of this amine, whereas, acetaldehyde produced profound aberrations in NE metabolism. The excretion of ¹⁴C-vanillylmandelic acid and dihydroxymandelic acid was decreased as a result of treatment with acetaldehyde, disulfiram, or calcium carbimide. A concomitant increase in labeled 3-methoxy-4-hydroxyphenylglycol was also observed with these treatments. Administration of ethanol to animals previously treated with disulfiram or calcium carbimide potentiated this effect and resulted in elevated acetaldehyde blood levels as measured by a specific gas chromatographic procedure. These findings confirm the hypothesis that competitive inhibition of aldehyde dehydrogenase by acetaldehyde is the quantitatively important mechansim in the genesis of altered neuroamine metabolism by ethanol.

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