Acetaminophen inhibits liver tryptophan-2,3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindole acetic acid

The effect of the analgesic agent, acetaminophen was determined on rat fore brain serotonin levels as well as hepatic tryptophan-2,3-dioxygenase (TDO) activity and urinary 5-hydroxyindole acetic acid (5-HIAA). The results show that acetaminophen administration (100mg/kg) over three hours does not aff ect the holoenzyme of tryptophan-2,3-dioxygenase but significantly inhibits the apoenzyme. This inhibition is accompanied by a concomitant rise in for ebrain serotonin levels. This phenomenon is also accompanied by a reduction in urinary 5-HIAA levels. These results suggest that acetaminophen use is ac companied by changes in brain serotonin levels due to inhibition of hepa tic tryptophan-2,3-dioxygenase activity. This in turn could explain the pos sible abuse potential of acetaminophen and its effects on mood at high dose s. (C) 2000 Elsevier Science Inc. All rights reserved.