The metabolism of [2-14C] indole in the rat.

1. [2-(14)C]Indole has been synthesized from [(14)C]formate and o-toluidine via N[(14)C]-formyltoluidine. 2. When fed to rats, the (14)C of [(14)C]indole (dose 70-80mg./kg. body wt.) is fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air. 3. Radioactivity is excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5.8%), 5-hydroxyoxindole conjugates (3.1%), N-formylanthranilic acid (0.5%) and unchanged indole (0.07%). The faeces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. 4. Fed to rats with biliary cannulae an average of 5.6% of a dose of [(14)C]indole (20-60mg./kg. body wt.) is excreted in the bile in 2 days. Radioactivity is present as indoxyl sulphate (0.8% dose) and 5-hydroxyoxindole conjugates (0.6%). 5. Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole. 6. With rat-liver microsomes plus supernatant under aerobic conditions, indole gives indoxyl, oxindole, possibly isatin, N-formylanthranilic acid and anthranilic acid, but under anaerobic conditions gives only oxindole. Similarly, under aerobic conditions, oxindole gives 5-hydroxyoxindole, anthranilic acid and o-aminophenylacetic acid. 7. Indole is metabolized by two pathways, one via indoxyl to isatin, N-formylanthranilic acid and anthranilic acid, and the other via oxindole to 5-hydroxyoxindole and possibly to o-aminophenylacetic and anthranilic acid. 8. The following new compounds are described: 4-hydroxy-2-nitrophenylacetic acid, 3-, 4- and 5-benzyloxy-2-nitrophenylacetic acid, 5- and 7-hydroxyoxindole and 5-aminoacridine indoxyl sulphate.