1,3-Dimethyluric acid is an active metabolite of the methylxanthine alkaloids caffeine and theophylline .1 It is formed from caffeine and theophylline by the cytochrome P450 (CYP) isoforms CYP1A2 and CYP2E1.2,3 1,3-Dimethyluric acid (500 ?M) scavenges hydroxyl radicals in a cell-free assay and inhibits t-butyl hydroperoxide-induced lipid peroxidation by 77% in isolated human erythrocyte membranes.4 It induces contractions in isolated rabbit duodenal, jejunal, and ileal preparations, but induces relaxation in isolated rabbit ascending colon preparations, in a concentration-dependent manner.5 Intracerebral administration of 1,3-dimethyluric acid induces clonic convulsions in mice (ED50 = 360 nmol/animal).6 It has been found in urinary caliculi.7
1.Cornish, H.H., and Christman, A.A.A study of the metabolism of theobromine, theophylline, and caffeine in manJ. Biol. Chem.228(1)315-323(1957) 2.Caubet, M.-S., Elbast, W., Dubuc, M.-C., et al.Analysis of urinary caffeine metabolites by HPLC-DAD: The use of metabolic ratios to assess CYP1A2 enzyme activityJ. Pharm. Biomed. Anal.27(1-2)261-270(2002) 3.Fuhr, U., Doehmer, J., Battula, N., et al.Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Allocation of metabolic pathways to isoforms and inhibitory effects of quinolonesToxicology82(1-3)169-189(1993) 4.Bhat, V.B., Sridhar, G.R., and Madyastha, K.M.Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-trimethyluric acidLife Sci.70(4)381-393(2001) 5.Psarra, T.A., Batzias, G.C., Peeters, T.L., et al.Theophylline and its metabolites produce a stimulating cholinergic effect on the small intestine and a nonadrenergic noncholinergic relaxing effect on the colon: A comparative study in the rabbit intestineJ. Vet. Pharmacol. Ther.30(6)541-519(2007) 6.Yamamoto, K., Toyama, E., Kawakami, J., et al.Neurotoxic convulsions induced by theophylline and its metabolites in miceBiol. Pharm. Bull.19(6)869-872(1996) 7.Safranow, K., and Machoy, Z.Methylated purines in urinary stonesClin. Chem.51(8)1493-1498(2005)