Abstract

The effect of short-term oral administration of doxepin, a tricyclic antidepressant, on voluntary drinking of ethanol was studied in the rat as a function of sex. The effects of doxepin on ethanol and acetaldehyde metabolizing enzymes of hepatic and selected endocrine tissues were made in the presence and in the absence of ethanol. A reduction in voluntary ethanol intake was determined after the initial doxepin dose. This effect was not apparent during continued drug administration. Subsequently, a statistically insignificant reduction of ethanol drinking was noted 24 h and 72 h post-drug termination. Hepatic alcohol and aldehyde dehydrogenase were not altered from respective controls by doxepin in the presence and absence of ethanol. Epididymal and testicular adlehyde dehydrogenase were inhibited by doxepin from control in rats maintained on ethanol or water, respectively. The results suggest lack of adverse effect of doxepin on peripheral metabolism of alcohol metabolizing enzymes as compared to adverse interaction with acetaldehyde metabolizing enzyme in the endocrine tissues studied.

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