Species difference in the metabolism of L-5-hydroxy-tryptophan and 5-hydroxytryptamine in mice, rats, dogs, and monkeys.

The biotransformation of exogenous L-5-hydroxytryptophan (L-5-HTP), an antidepressant agent, was studied in mice, rats, dogs and monkeys after an oral administration of L-5-HTP-3-14C (5 mg/kg). The major metabolites in urine were 5-hydroxyindole acetic acid (5-HIAA) and its conjugates in mice, dogs and monkeys, accounting for about 60% of the total urinary metabolites. In rats, in contrast to other species, 5-hydroxytryptamine (5-HT) glucuronide was the major metabolite (60%), and 5-HIAA and its conjugates were minor. This species difference in the urinary metabolites was more clearly observed when 5-HT-14C was orally administered. In monkeys, a specific metabolite was detected in the urine after administration of both L-5-HTP and 5-HT and identified as a conjugate of 3-methyl-5-hydroxyindole. The species difference observed may be related to the fact that a renal toxicity occurs only in rats after an oral administration of L-5-HTP or 5-HT. In order to explain the species difference in L-5-HTP metabolism, the activities of glucuronyltransferase, monoamine oxidase and aromatic amino acid decarboxylase were compared in the liver, kidney and small intestine from the four animal species. The glucuronyltransferase activity in the rat tissues was found to be much higher than that in the other animal species.