Acetaminophen inhibits liver trytophan-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 forebrain 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 affect the holoenzyme of tryptophan-2,3-dioxygenase but significantly inhibits the apoenzyme. This inhibition is accompanied by a concomitant rise in forebrain serotonin levels. This phenomenon is also accompanied by a reduction in urinary 5-HIAA levels. These results suggest that acetaminophen use is accompanied by changes in brain serotonin levels due to inhibition of hepatic tryptophan-2,3-dioxygenase activity. This in turn could explain the possible abuse potential of acetaminophen and its effects on mood at high doses.
Daya
S
S
Department of Pharmacy, Rhodes University, Grahamstown, South Africa. s.daya@ru.ac.za
Anoopkumar-Dukie
S
S
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001051:Apoenzymes / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*
D018712:Analgesics, Non-Narcotic; D001051:Apoenzymes; D004791:Enzyme Inhibitors; D012701:Serotonin; D000082:Acetaminophen; D006897:Hydroxyindoleacetic Acid; D014366:Tryptophan Oxygenase