Inhibition of rat liver tryptophan pyrrolase activity by fluoxetine

The present study has demonstrated the effectiveness of acute administration of fluoxetine to inhibit rat liver tryptophan pyrrolase activity. The maximum inhibition of basal liver tryptophan pyrrolase activity at 2 h after administration was observed with 1 mg/kg dose for the total enzyme and apoenzyme activities and that significant inhibition of these two activities was evident with a dose of the drug as small as 0.5 mg/kg. Serum free tryptophan concentrations were also increased using 10 mg/kg dose of fluoxetine. In view of the role of tryptophan depletion and thus 5-HT in pathophysiology of depression, it is strongly suggested that the inhibition of liver tryptophan pyrrolase activity may be a major mechanism of antidepressant action.