Papaverine, tetrahydropapaverine and ethanol metabolizing enzymes

The effects of tetrahydropapaverine (THP) and papaverine (PAP), an O-methylated analogue, on rat liver alcohol dehydrogenase (L-ADH) and aldehyde-dehydrogenase (L-ALDH) were studied in vitro. The action of THP on these enzymes was also evaluated in vivo in conjunction with its effect on voluntary intake of ethanol by the rat. Both L-ADH and mitochondrial L-ALDH were inhibited in vitro in the presence of 10(-4) M THP. Conversely, stimulation of L-ADH and L-ALDH occurred by PAP in the concentration range between 10(-4) to 10(-6) M in vitro. Acute or daily administration of THP for five consecutive days did not alter voluntary intake of ET by the rat or changed specific activity of these hepatic enzymes in vivo. The structure activity of these compounds in relationship to the enzymes studied suggest the importance of O-methylation on the enzymatic effect studied which may possibly underlie some of the hypothesized action of THP on libation of alcohol.