METABOLIC PATHWAY OF THEOBROMINE IN THE RAT AND IDENTIFICATION OF 2 NEW METABOLITES IN HUMAN-URINE

Theobromine, a metabolite of caffeine, is present in food and is also used in pharmacology as a diuretic. [7-mei-14C] Theobromine was synthesized and administered by stomach tube to six rats. Twenty-four hours later, the radioactivity collected in U C02, feces, and urine amounted respectively to 6 ± 1, 11 ± 1, and 84 ± 8% of the total dose. Less than 3% of the radioactivity was found in the body of the animal. Compounds identified in the urine were theobromine (49% of the urine radioactivity), 7-methylxanthine (6%), and 7-methyluric acid (4%). Two new metabolites, 3, 7-dimethyluric acid (2, 7%) and 4-amino-5-(AT-methylformylamino)-3-methyluracil (36%), were identified and also low amounts of dimethylallantoin and V-methylurea. 3-Methylxanthine, a pharmacologically active metabolite of theophylline, and 3-methyluric acid amounted to 5.8% and corresponded to a minor metabolic pathway in the case of theobromine. 3, 7-Dimethyluric acid and the uracil derivative were identified in human urine. © 1979, American Chemical Society. All rights reserved.