Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of antidepressants

Abstract

The apoenzyme activity of rat liver tryptophan pyrrolase is decreased in vitro by 16–100% by concentrations of many antidepressants of 0.01–1 mM. Apo-(tryptophan pyrrolase) activity is also decreased by 37–86% at 2hr after administration of a 10 mg/kg dose of many antidepressants. This inhibition appears to be due to the prevention of the conjugation of the apoenzyme with its cofactor haem. Brain tryptophan concentration is elevated by 19–39% at 3.5 hr after administration of the above dose of antidepressants. Isocarboxazid is the only antidepressant tested that affects neither liver pyrrolase activity nor brain tryptophan concentration. The non-antidepressants chlorpromazine, β-flupenthixol, mefenamic acid and pargyline are also ineffective in both respects. The increase in brain tryptophan concentration caused by administration of mianserin, viloxazine, desipramine or tranylcypromine is associated with an accumulation of tryptophan in the liver and an increased availability of the circulating amino acid to the brain. It is suggested that antidepressants increase brain tryptophan concentration by inhibiting liver tryptophan pyrrolase activity. The results are briefly discussed in relation to the therapeutic effects of the drugs.