Interactions of pyrazole and ethanol on norepinephrine metabolism in rat brain

Single large doses of pyrazole (100-200 mg/kg) given either i.p. or orally caused a decrease in brain norepinephrine and 3-methoxy-4-hydroxyphenylethylene glycol sulfate, but no change in dopamine beta-hydroxylase activity. The effects were enhanced by daily administration for 3 to 4 days. Concomitant administration of ethanol prevented the effects. With smaller doses (50 mg/kg/day) given orally for several days, there was little or no change for 3 days, but after 6 days there was an increase in both parameters. Dopamine beta-hydroxylase activity was also increased. The daily administration of ethanol alone (6.0 g/kg/day) for 6 days caused increased norepinephrine, but 3-methoxy-4-hydroxyphenylene glycol sulfate was diminished and dopamine beta-hydroxylase was unaffected. When the two drugs were given simultaneously, steady-state levels of norepinephrine were unaltered, but the sulfate metabolite was increased as was dopamine beta-hydroxylase. The results suggest that pyrazole and/or ethanol, administered daily for 6 days, leads to adaptive responses in catecholamine metabolism. Pyrazole (or a metabolite) has marked effects of its own, some or all of which are independent of its effects on alcohol dehydrogenase. When the two drugs are administered together, it is difficult to know whether the observed changes are independent or overlapping effects.