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Uric Acid pp 485–514Cite as

Allopurinol and Other Inhibitors of Urate Synthesis

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Part of the Handbook of Experimental Pharmacology book series (HEP,volume 51)

Abstract

The ideal drug for the treatment of hyperuricemia would be one which reduces uric acid synthesis without interfering with important anabolic pathways or normal regulatory functions. In theory, uric acid production may be inhibited at a number of different enzymatic steps, either those involved in the de novo pathway of purine biosynthesis or those concerned with the final stages of purine catabolism. Compounds such as azaserine and diazo-oxo-norleucine which block the early steps of purine biosynthesis reduce uric acid synthesis but also interfere with nucleic acid synthesis and are therefore cytotoxic (Grayzel et al., 1960; Zuckerman et al., 1959). Inhibition of xanthine oxidase, on the other hand, has proven to be a clinically safe and effective method of reducing uric acid formation.

Keywords

  • Uric Acid
  • Xanthine Oxidase
  • Orotic Acid
  • Purine Nucleoside Phosphorylase
  • Xanthine Oxidase Inhibitor

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  • Ablin, A., Stephens, B.G., Hirata, T., Wilson, K., Williams, H.E.: Nephropathy, xanthinuria, and orotic aciduria complicating Burkitt’s lymphoma treated with chemotherapy and allopurinol. Metabolism 21, 771–778 (1972)

    PubMed  CAS  Google Scholar 

  • Alberts, D.S., Van Dallen Wetters, T.: Allopurinol potentiates cyclophosphamide antileukemic activity. Proc. Amer. Ass. Cancer Res. 16, 84 (1975)

    Google Scholar 

  • Alexander, J.A., Wheeler, G.P., Hill, D.D., Morris, H.P.: Effects of 4-hydroxypyrazolo(3,4-d)pyrimidine upon the catabolism of purines by various tissues of the rat and upon the rate of growth of Morris 5123-C hepatoma. Biochem. Pharmacol. 15, 881–889 (1966)

    PubMed  CAS  Google Scholar 

  • Alken, C.E., May, P., Braun, J.S.: Analysis of treatment results in uric acid lithiasis with and without hyperuricemia. Advanc. exp. Med. Biol. 41B, 535–540 (1974)

    Google Scholar 

  • Auscher, C., Mercier, N., Pasquier, C.: Allopurinol and thiopurinol: effect in vivo on urinary oxypurine excretion and rate of synthesis of their ribonucleotides in different enzymatic deficiencies. Advanc. exp. Med. Biol. 41B, 657–662 (1974a)

    CAS  Google Scholar 

  • Auscher, C., Pasquier, C., Mercier, N., Delbarre, F.: Urinary excretion of 6-hydroxylated metabolite and oxypurines in a xanthinuric man given allopurinol or thiopurinol. Advanc. exp. Med. Biol. 41B, 663–667 (1974)

    Google Scholar 

  • Ayvazian, J.H.: Xanthinuria and hemochromatosis. New Engl. J. Med. 270, 18–22 (1964)

    PubMed  CAS  Google Scholar 

  • Badawy, A.A.-B., Evans, M.: The mechanism of rat liver tryptophan pyrrolase activity by 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol). Biochem. J. 133, 585–591 (1973)

    PubMed  CAS  Google Scholar 

  • Badawy, A.A., Evans, M.: Tryptophan plus a pyrrolase inhibitor for depression? Lancet 1974 II, 1209–1210

    Google Scholar 

  • Bagley, C.M., Jr., Bostick, F.W., De Vita, V.T., Jr.: Clinical pharmacology of cyclophosphamide. Cancer Res. 33, 226–233 (1973)

    PubMed  Google Scholar 

  • Baker, C. H.: Protection against irreversible haemorrhagic shock by allopurinol. Proc. Soc. exp. Biol. (N.Y.) 141, 694–698 (1972)

    CAS  Google Scholar 

  • Balis, M.E., Krakoff, I.H., Berman, P.H., Dancis, J.: Urinary metabolites in congenital hyperuricosuria. Science 156, 1122–1123 (1967)

    PubMed  CAS  Google Scholar 

  • Band, P.R., Silverberg, D.S., Henderson, J.F, Ulan, R.A., Wensel, R.H., Bannerjee, T.K, Little, A.S.: Xanthine nephropathy in a patient with lymphosarcoma treated with allopurinol. New Engl. J. Med. 283, 354–357 (1970)

    PubMed  CAS  Google Scholar 

  • Beardmore, T.D., Cashman, J.S., Kelley, W.N.: Mechanism of allopurinol-mediated increase in cultured human fibroblasts. J. clin. Invest. 51, 1823–1832 (1972)

    PubMed  CAS  Google Scholar 

  • Beardmore, T.D., Kelley, W.N.: Mechanism of allopurinol-mediated inhibition of pyrimidine biosynthesis. J. Lab. clin. Med. 78, 696–704 (1971)

    PubMed  CAS  Google Scholar 

  • Becker, M.A., Argubright, K.F., Fox, R.M., Seegmiller, J.E.: Oxipurinol-associated inhibition of pyrimidine synthesis in human lymphoblasts. Molec. Pharmacol. 10, 657–668 (1974)

    CAS  Google Scholar 

  • Becking, G.C., Johnson, W.J.: The inhibition of tryptophan pyrrolase by allopurinol, an inhibitor of xanthine oxidase. Canad. J. Biochem. 45, 1667–1672 (1967)

    CAS  Google Scholar 

  • Becking, G.C., Johnson, W.J.: Pyrazolo-and triazolopyrimidines as inhibitors of tryptophan pyrrolase. Life Sci. 8II, 843–851 (1969)

    Google Scholar 

  • Boston Collaborative Drug Surveillance Program: Excess of ampicillin rashes associated with allopurinol or hyperuricemia. New Engl. J. Med. 286, 505–507 (1972)

    Google Scholar 

  • Boston Collaborative Drug Surveillance Program: Allopurinol and cytotoxic drugs. Interaction in relation to bone marrow depression. J. Amer. med. Ass. 227, 1036–1040 (1974)

    Google Scholar 

  • Boyett, J.D., Vogler, W.R., Furtado, V. de P., Schmidt, F.H.: Allopurinol and iron metabolism in man. Blood 32, 460–468 (1968)

    PubMed  CAS  Google Scholar 

  • Brown, G.K., Fox, R.M., O’Sullivan, W.J.: Alteration of quaternary structural behavior of an hepatic orotate phosphoribosyltransferase-orotidine-5′-phosphate decarboxylase complex in rats following allopurinol therapy. Biochem. Pharmacol. 21, 2469–2477 (1972)

    PubMed  CAS  Google Scholar 

  • Brown, G.K., Fox, R.M., O’Sullivan, W.J.: Interconversion of different molecular weight forms of human erythrocyte orotidylate decarboxylase. J. biol. Chem. 250, 7352–7358 (1975)

    PubMed  CAS  Google Scholar 

  • Buchanan, J.M., Flaks, J.G., Hartman, S.C., Levenberg, B., Lukens, L.N, Warren, L.: The enzymatic synthesis of inosinic acid de novo. In: Wolstenholme, G.E.W., O’Connor, C.M. (Eds.): Chemistry and Biology of Purines, Ciba Foundation Symposium, May 1956, pp. 233–252. Boston: Little Brown 1957

    Google Scholar 

  • Burroughs Wellcome Co.: Unpublished reports

    Google Scholar 

  • Byers, S.O.: Xanthine oxidase studies. J. Amer, pharm. Ass. sci. Ed. 41, 611–613 (1952)

    CAS  Google Scholar 

  • Cartier, P.H., Hamet, M.: Mechanism of antiuric action of 4-oxy- and 4-thiopyrazolopyrimidines. Biochem. Pharmacol. 22, 3061–3075 (1973)

    PubMed  CAS  Google Scholar 

  • Chalmers, R.A., Krorner, H., Scott, J.T., Watts, R.W.E.: A comparative study of the xanthine oxidase inhibitors allopurinol and oxipurinol in man. Clin. Sci. 35, 353–362 (1968)

    PubMed  CAS  Google Scholar 

  • Chalmers, R.A., Parker, R., Simmonds, H.A., Snedden, W., Watts, R.W.E.: The conversion of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) into 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in vivo in the absence of xanthine-oxygen oxido reductase. Biochem. J. 112, 527–532(1969)

    PubMed  CAS  Google Scholar 

  • Chatterjee, S.N., Berne, T.V.: Protective effect of allopurinol in renal ischemia. Amer. J. Surg. 131, 658–659(1976)

    PubMed  CAS  Google Scholar 

  • Chytil, F.: Activation of liver tryptophan oxygenase by adenosine 3’,5’-phosphate and by other purine derivatives. J. biol. Chem. 243, 893–899 (1968)

    PubMed  CAS  Google Scholar 

  • Clifford, A., Riumallo, J.A., Baliga, B.S., Munro, H.N., Brown, P.R.: Liver nucleotide metabolism in relation to amino acid supply. Biochim. biophys. (Amst.) Acta 277, 443–458 (1972)

    CAS  Google Scholar 

  • Coe, F. L., Kavalach, A.G.: Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis. New Engl. J. Med. 291, 1344–1350 (1974)

    PubMed  CAS  Google Scholar 

  • Coe, F.L., Lawton, R.L., Goldstein, R.B., Tembe, V.: Sodium urate accelerates precipitation of calcium oxalate in vitro. Proc. Soc. exp. Biol. (N.Y.) 149, 926–929 (1975)

    CAS  Google Scholar 

  • Coe, F.L., Raiser, L.: Allopurinol treatment of uric acid disorders in calcium stone formers. Lancet 1973 I, 129–131

    Google Scholar 

  • Coffey, J. J., White, C.A., Lesk, A.B., Rogers, W.I., Serpick, A.A.: Effect of allopurinol on the pharmacokinetics of 6-MP in cancer patients. Cancer Res. 32, 1283–1289 (1972)

    PubMed  CAS  Google Scholar 

  • Crowell, J.W.: Oxygen transport in the hypotensive state. Fed. Proc. 29, 1848–1853 (1970)

    PubMed  CAS  Google Scholar 

  • Crowell, J.W., Jones, C.E., Smith, E.E.: Effect of allopurinol on hemorrhagic shock. Amer. J. Physiol. 216, 744–748 (1969)

    PubMed  CAS  Google Scholar 

  • Cunningham, S.K., Keaveny, T.V., Fitzgerald, P.: Effect of allopurinol on tissue ATP, ADP, and AMP concentrations in renal ischaemia. Brit. J. Surg. 61, 562–565 (1974)

    PubMed  CAS  Google Scholar 

  • Davis, P.S., Deller, D.J.: Effect of a xanthine oxidase inhibitor (allopurinol) on radio-iron absorption in man. Lancet 1966 II, 470–472

    Google Scholar 

  • Dean, B.M., Perrett, D., Simmonds, H.A., Grahame, R.: Thiopurinol: comparative enzyme inhibition and protein binding studies with allopurinol, oxipurinol and 6-mercaptopurine. Brit. J. clin. Pharmacol. 1, 119–127 (1974)

    CAS  Google Scholar 

  • Delbarre, F., Auscher, C., DeGery, A., Brouilhet, H., Olivier, J.-L.: Le traitement de la dyspurin-urie goutteuse par la mercapto-pyrazolopyrimidine (M.P.P.: thiopurinol). Presse méd. 76, 2329–2332 (1968)

    PubMed  CAS  Google Scholar 

  • Delbarre, F., Auscher, C., Thang, K.V., Brouilhet, H., De Gery, A.: Effet de retroaction de certaines pyrazolopyrimidines sur le métabolisme de l’acide urique. CR. Acad. Sci. (Paris) 267, 2231–2234 (1968a)

    CAS  Google Scholar 

  • Delbarre, F., Cartier, P., Auscher, C., De Gery, A., Hamet, M.: Dyspurinies par déficit en hypoxanthine-guanine-phosphoribosyl-transferase. Fréquence et caractères cliniques de l’anenzymose. Presse méd. 78, 729–734 (1970)

    PubMed  CAS  Google Scholar 

  • De Vries, A., Frank, M.: Prophylaxis of idiopathic and gouty uric acid lithiasis by allopurinol. Urol. int. 22, 505–516 (1967)

    Google Scholar 

  • De Vries, A., Frank, M., Libermon, U.A., Sperling, O.: Allopurinol in the prophylaxis of uric acid stones. Ann. rheum. Dis. 25, 691–693 (1966)

    PubMed  Google Scholar 

  • De Vries, A., Sperling, O.: Recent data on uric acid lithiasis. Adv. Nephrol. 3, 89–116 (1974)

    Google Scholar 

  • De Wall, R.A., Vasko, K.A., Stanley, E.L., Kezdi, P.: The responses of the ischemic myocardium to allopurinol. Amer. Heart J. 82, 362–370 (1971)

    Google Scholar 

  • Duggan, D.E., Noll, R.M., Baer, J.E., Novello, F.C., Baldwin, J.J.: 3,5-Disubstituted-1,2,4-triazoles, a new class of xanthine oxidase inhibitor. J. med. Chem. 18, 900–905 (1975)

    PubMed  CAS  Google Scholar 

  • Edmondson, D., Massey, V., Palmer, G., Beacham, L.M., III, Elion, G.B.: The resolution of active and inactive xanthine oxidase by affinity chromatography. J. biol. Chem. 247, 1597–1604 (1972)

    PubMed  CAS  Google Scholar 

  • Elion, G. B.: Unpublished

    Google Scholar 

  • Elion, G.B.: Enzymatic and metabolic studies with allopurinol. Ann. rheum. Dis. 25, 608–614 (1966)

    PubMed  CAS  Google Scholar 

  • Elion, G.B.: Interaction of anticancer drugs with enzymes. In: Pharmacological Basis of Cancer Chemotherapy, pp. 547–564. Baltimore Maryland: Williams and Wilkins Co. 1975

    Google Scholar 

  • Elion, G.B., Benezra, F.M., Canellas, I., Carrington, L.O., Hitchings, G.H.: Effects of xanthine oxidase inhibitors on purine catabolism. Israel J. Chem. 6, 787–796 (1968)

    CAS  Google Scholar 

  • Elion, G.B., Bieber, S., Hitchings, G.H.: The fate of 6-mercaptopurine in mice. Ann. N.Y. Acad. Sci. 60, 297–303 (1954)

    PubMed  CAS  Google Scholar 

  • Elion, G.B., Callahan, S.W., Hitchings, G.H., Rundles, R.W., Laszlo, J.: Experimental, clinical, and metabolic studies of thiopurines. Cancer Chemother. Rep. 16, 197–202 (1962)

    PubMed  CAS  Google Scholar 

  • Elion, G.B., Callahan, S., Nathan, H., Bieber, S., Rundles, R. W., Hitchings, G.H.: Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem. Pharmacol. 12, 85–93 (1963)

    CAS  Google Scholar 

  • Elion, G.B., Callahan, S., Rundles, R.W., Hitchings, G.H.: Relationship between metabolic fates and antitumor activities of thiopurines. Cancer Res. 23, 1207–1217 (1963a)

    PubMed  CAS  Google Scholar 

  • Elion, G.B., Hitchings, G.H.: Azathioprine. In: Sartorelli, A.C., Johns, D.G. (Eds.): Handbook of experimental pharmacology, New Series, Vol. 38, Pt. 2, pp. 404–425. Berlin-Heidelberg-New York: Springer 1975

    Google Scholar 

  • Elion, G.B., Kovensky, A., Hitchings, G.H., Metz, E., Rundles, R.W.: Metabolic studies of allopurinol, an inhibitor of xanthine oxidase. Biochem. Pharmacol. 15, 863–880 (1966)

    PubMed  CAS  Google Scholar 

  • Elion, G.B., Mueller, S., Hitchings, G.H.: Studies on condensed pyrimidine systems XXI. The isolation of synthesis of 6-mercapto-2,8-purinediol (6-thiouric acid). J. Amer. chem. Soc. 81, 3042–3045 (1959)

    CAS  Google Scholar 

  • Elion, G.B., Nelson, D.J.: Ribonucleotides of allopurinol and oxipurinol in rat tissues and their significance in purine metabolism. Advanc. exp. Med. Biol. 41B, 639–652 (1974)

    CAS  Google Scholar 

  • Elion, G.B., Yu, T.-F., Gutman, A.B., Hitchings, G.H.: Renal clearance of oxipurinol, the chief metabolite of allopurinol. Amer. J. Med. 45, 69–77 (1968)

    PubMed  CAS  Google Scholar 

  • Ellis, C.H., Touw, K.B., Dickerson, S.W.: Some acute hemodynamic effects of large doses of sodium allopurinol in open-chested dogs. Arch. int. Pharmacodyn. Therap. 205, 355–367 (1973)

    CAS  Google Scholar 

  • Emmerson, B.T.: Effect of allopurinol on iron metabolism in man. Ann. rheum. Dis. 25, 700–703 (1966)

    PubMed  CAS  Google Scholar 

  • Engelman, K., Watts, R.W.E., Klineberg, J.R., Sjoerdsma, A., Seegmiller, J.E.: Clinical, physiological and biochemical studies of a patient with xanthinuria and pheochromocytoma. Amer. J. Med. 37, 839–861 (1964)

    PubMed  CAS  Google Scholar 

  • Fox, I.H., Kelley, W.N.: Phosphoribosylpyrophosphate in man: biochemical and clinical significance. Ann. intern. Med. 74, 424–433 (1971)

    PubMed  CAS  Google Scholar 

  • Fox, I.H., Wyngaarden, J.B., Kelley, W.N.: Depletion of erythrocyte phosphoribosylpyrophosphate in man—a newly observed effect of allopurinol. New Engl. J. Med. 283, 117–1182 (1970)

    Google Scholar 

  • Fox, R.M., Royse-Smith, D., O’Sullivan, W.J.: Orotidinuria induced by allopurinol. Science 168, 861–862(1970)

    PubMed  CAS  Google Scholar 

  • Fox, R.M., Wood, M.H., O’Sullivan, W.J.: Studies on the coordinate activity and lability of orotidylate phosphoribosyl transferase and decarboxylase in human erythrocytes, and the effects of allopurinol administration. J. clin. Invest. 50, 1050–1060 (1971)

    PubMed  CAS  Google Scholar 

  • Fyfe, J.A., Miller, R.L., Krenitsky, T.A.: Kinetic properties and inhibition of orotidine 5’-phos-phate decarboxylase. J. biol. Chem. 248, 3801–3809 (1973)

    PubMed  CAS  Google Scholar 

  • Fyfe, J.A., Nelson, D.J., Hitchings, G.H.: The molecular basis of the effects of allopurinol on pyrimidine metabolism. Adv. exp. Med. Biol. 41B, 621–628 (1974)

    CAS  Google Scholar 

  • Gevirtz, N.R.: Allopurinol and iron metabolism. Lancet 1967 II, 715

    Google Scholar 

  • Glogner, P.: Metabolism of tolbutamide and cyclamate. Hum. Genet. 9, 230–232 (1970)

    CAS  Google Scholar 

  • Goldfinger, S., Klinenberg, J.R., Seegmiller, J.E.: The renal excretion of oxypurines. J. clin. Invest. 44, 623–628(1965)

    PubMed  CAS  Google Scholar 

  • Grace, N.D., Greenwald, M.A., Greenberg, M.S.: Effect of allopurinol on iron mobilization. Gastroenterology 59, 103–108 (1970)

    PubMed  CAS  Google Scholar 

  • Grahame, R., Simmonds, H.A., Cadenhead, A., Dean, B.M.: Metabolic studies of thiopurinol in man and pig. Advanc. exp. Biol. Med. 41B, 597–605 (1974)

    CAS  Google Scholar 

  • Grahame, R., Simmonds, H.A., Cameron, J.S., Cadenhead, A.: Thiopurinol: dose related effect on urinary oxypurine excretion. J. clin. Chem. clin. Biochem. 14, 291 (1976)

    Google Scholar 

  • Grayzel, A., Seegmiller, J.E., Lane, E.: Suppression of uric acid synthesis in the gouty human by the use of 6-diazo-5-oxo-L-norleucine. J. clin. Invest. 39, 447–454 (1960)

    PubMed  CAS  Google Scholar 

  • Green, A.R., Curzon, G.: Decrease of 5-hydroxytryptamine in the brain provoked by hydrocortisone and its prevention by allopurinol. Nature (Lond.) 220, 1095–1097 (1968)

    CAS  Google Scholar 

  • Green, R., Levin, N.W., Samassa, D., Charlton, R.W., Bothwell, T.H.: The effect of allopurinol on iron metabolism. S. Afr. med. J. 42, 776–779 (1968)

    CAS  Google Scholar 

  • Green, A.R., Woods, H.F., Joseph, M.H.: Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation. Brit. J. Pharmacol. 57, 103–114 (1976)

    CAS  Google Scholar 

  • Greenberg, R.: Discussion. In: Wolstenholme, G.E.W., O’Conner, C.M. (Eds.): Chemistry and Biology of Purines, Ciba Foundation Symposium, May 1956, p. 267. Boston: Little Brown 1957

    Google Scholar 

  • Greene, M.L., Fujimoto, W.Y., Seegmiller, J.E.: Urinary xanthine stones—a rare complication of allopurinol therapy. New Engl. J. Med. 280, 426–427 (1969)

    PubMed  CAS  Google Scholar 

  • Grindey, G.B., Moran, R.G.: Effects of allopurinol on the therapeutic efficacy of methotrexate. Cancer Res. 35, 1702–1705 (1975)

    PubMed  CAS  Google Scholar 

  • Grobner, W., Kelley, W.N.: Effect on allopurinol and its metabolic derivatives on the configuration of human orotate phosphoribosyltransferase and orotidine 5’-phosphate decarboxylase. Biochem. Pharmacol. 24, 379–384 (1975)

    PubMed  CAS  Google Scholar 

  • Gutman, A.B., Yii, T.-F.: Uric acid nephrolithiasis. Amer. J. Med. 45, 756–779 (1968)

    PubMed  CAS  Google Scholar 

  • Hamilton, L., Elion, G.B.: The fate of 6-mercaptopurine in man. Ann. N.Y. Acad. Sci. 60, 304–314(1954)

    PubMed  CAS  Google Scholar 

  • Haskovec, L., Dostal, T., Jirak, R.: The action of allopurinol as an inhibitor of liver tryptophan pyrrolase in depressions. Activ. nerv. sup. (Praha) 14, 131–132 (1972)

    CAS  Google Scholar 

  • Hatfield, D., Wyngaarden, J.B.: 3-ribosylpurines. I. Synthesis (3-ribosyluric acid)5′-phosphate and (3-ribosylxanthine)5′-phosphate by a pyrimidine ribonucleotide pyrophosphorylase of beef erythrocytes. J. biol. Chem. 239, 2580–2586 (1964)

    PubMed  CAS  Google Scholar 

  • Hatfield, D., Wyngaarden, J.B.: II. Studies on (3-ribosylxanthine)-5′-phosphate and on ribonucleotide derivatives of certain uracil analogues. J. biol. Chem. 239, 2587–2592 (1964a)

    PubMed  CAS  Google Scholar 

  • Hayes, C.P., Jr., Metz, E.N., Robinson, R.R., Rundles, R.W.: The use of allopurinol (HPP) to control hyperuricemia in patients on chronic intermittent hemodialysis. Trans. Amer. Soc. artif. internal Org. 11, 247–251 (1965)

    Google Scholar 

  • Hillier, J., Hillier, J.G., Redfern, P.H.: Liver tryptophan pyrrolase activity and metabolism of brain 5-HT in rat. Nature (Lond.) 253, 566–567 (1975)

    CAS  Google Scholar 

  • Hitchings, G.H.: Effects of allopurinol in relation to purine biosynthesis. Ann. rheum. Dis. 25, 601–607(1966)

    PubMed  CAS  Google Scholar 

  • Hitchings, G.H.: Allopurinol, an inhibitor of xanthine oxidase; physiological and biochemical studies. In: Shugar, D. (Ed.): FEBS Symposium, Biochemical Aspects of Antimetabolites and of Drug Hydroxylation, Vol. 16, pp. 11–22. London-New York: Academic Press 1969

    Google Scholar 

  • Hitchings, G.H.: Crystals in skeletal muscle. Brit. med. J. 1971 IV, 555 (1971)

    Google Scholar 

  • Hitchings, G.H.: Indications for control mechanisms in purine and pyrimidine biosynthesis as revealed by studies with inhibitors. In: Advances in enzyme regulation, Vol. 12, pp. 121–129. Oxford: Pergamon 1974

    Google Scholar 

  • Hitchings, G.H.: Pharmacology of allopurinol. Arthr. and Rheum. 18, 863–870 (1975)

    CAS  Google Scholar 

  • Hitchings, G.H., Elion, G.B.: Mechanisms of action of purine and pyrimidine analogues. In: Brodsky, I., Kahn, S.B., Mover, J.H. (Eds.): Cancer Chemotherapy II, 22nd Hahnemann Symposium, pp. 23–32. New York: Grune and Stratton 1972

    Google Scholar 

  • Hoenig, V., Brodanonva, M., Strejcek, J., Kordac, V.: Allopurinol and iron metabolism. Lancet 1967 I, 387

    Google Scholar 

  • Holmes, E.W., Mason, D.H., Goldstein, L.I., Blount, R.E., Kelley, W.N.: Xanthine oxidase deficiency: studies of a previously unreported case. Clin. Chem. 20, 1076–1079 (1974)

    PubMed  Google Scholar 

  • Hopkins, R.W., Abraham, J., Simeone, F.A., Damewood, C.A.: Effect of allopurinol on hepatic adenosine nucleotides in hemhorrhagic shock. J. Surg. Res. 19, 381–390 (1975)

    PubMed  CAS  Google Scholar 

  • Imai, S., Riley, A.L., Berne, R.M.: Effect of ischemia on adenine nucleotides in cardiac and skeletal muscle. Circulat. Res. 15, 443–450 (1964)

    PubMed  CAS  Google Scholar 

  • Iwata, H., Yamamoto, J., Huh, K.: Sex differences in allopurinol oxidizing enzyme activity in mouse liver supernatant fraction. Biochem. Pharmacol. 23, 1144–1146 (1974)

    PubMed  CAS  Google Scholar 

  • Iwata, H., Yamamoto, J., Muraki, K., Goda, E.: Sex differences of acute toxicity in rats and mice. In: 1st Symp. on Drug Metabolism and Action, Chiba, Japan, Nov. 1969, pp. 124–129

    Google Scholar 

  • Jones, C.E., Crowell, J.W., Smith, E.E.: Significance of increased blood uric acid following extensive hemhorrage. Amer. J. Physiol. 214, 1374–1377 (1968)

    PubMed  CAS  Google Scholar 

  • Julian, J., Chytil, E.: Participation of xanthine oxidase in the activation of liver tryptophan pyrrolase. J. biol. Chem. 245, 1161–1168 (1970)

    PubMed  CAS  Google Scholar 

  • Kann, H.E, Jr., Wells, J.H., Galleli, J.F., Schein, P.S., Cooney, D.A., Smith, E.R., Seegmiller, J.E., Carbone, P.P.: The development and use of an intravenous preparation of allopurinol. Amer. J. med. Sci. 256, 53–63 (1968)

    PubMed  CAS  Google Scholar 

  • Kelley, W.N., Beardmore, T.D.: Allopurinol: Alteration in pyrimidine metabolism in man. Both allopurinol and oxypurinol inhibit de novo pyrimidine biosynthesis. Science 169, 388–390 (1970)

    PubMed  CAS  Google Scholar 

  • Kelley, W.N., Beardmore, T.D., Fox, I.H., Meade, J.C.: Effects of allopurinol and oxipurinol on pyrimidine synthesis in cultured human fibroblasts. Biochem. Pharmacol. 20, 1471–1478 (1971)

    CAS  Google Scholar 

  • Kelley, W.M., Wyngaarden, J.B.: Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells. J. clin. Invest. 49, 602–609 (1970)

    PubMed  CAS  Google Scholar 

  • Klinenberg, J.R., Goldfinger, S.E., Seegmiller, J.E.: Effectiveness of the xanthine oxidase inhibitor allopurinol in the treatment of gout. Ann. intern. Med. 62, 639–647 (1965)

    PubMed  CAS  Google Scholar 

  • Kozma, C., Salvador, R.A., Elion, G.B.: Allopurinol and iron storage. Lancet 1967 II, 1040–1041

    Google Scholar 

  • Kozma, C., Salvador, R.A., Elion, G.B.: Chronic allopurinol administration and iron storage in mice. Life Sci. 7, 341–348 (1968)

    PubMed  CAS  Google Scholar 

  • Krakoff, I.H., Meyer, R.L.: Prevention of hyperuricemia in leukemia and lymphoma. Use of allopurinol, a xanthine oxidase inhibitor. J. Amer. med. Ass. 193, 89–94 (1965)

    Google Scholar 

  • Krakoff, I.H., Murphy, M.L.: Hyperuricemia in neoplastic disease in children: prevention with allopurinol, a xanthine oxidase inhibitor. Pediatrics 41, 52–56 (1968)

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A.: Purine nucleoside Phosphorylase: kinetics, mechanism, and specificity. Molec. Pharmacol. 3, 526–536 (1967)

    CAS  Google Scholar 

  • Krenitsky, T.A.: Tissue distribution of purine ribosyl and phosphoribosyl-transferase in the Rhesus monkey. Biochim. biophys. Acta (Amst.) 179, 506–509 (1969)

    CAS  Google Scholar 

  • Krenitsky, T.A., Elion, G.B., Henderson, A.M., Hitchings, G.H.: Inhibition of human purine nucleoside Phosphorylase. J. biol. Chem. 243, 2876–2881 (1968)

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A., Elion, G.B., Strelitz, R.A., Hitchings, G.H.: Ribonucleosides of allopurinol and oxoallopurinol. J. biol. Chem. 242, 2675–2682 (1967)

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A., Mellors, J.W., Barclay, R.K.: Pyrimidine nucleosidases. Their classification and relationship to uric acid ribonucleoside Phosphorylase. J. biol. Chem. 240, 1281–1286 (1965)

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A., Neil, S.M., Elion, G.B., Hitchings, G.H.: A comparison of the specificities of xanthine oxidase and aldehyde oxidase. Arch. Biochem. Biophys. 150, 585–599 (1972)

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A., Papaioannau, R., Elion, G.B.: Human hypoxanthine phosphoribosyltransferase. I. purification, properties, and specificity. J. biol. Chem. 244, 1263–1270 (1969)

    PubMed  CAS  Google Scholar 

  • Landgrebe, A.R., Nyhan, W.L., Coleman, M.: Urinary-tract stones resulting from the excretion of oxipurinol. New Engl. J. Med. 292, 626–627 (1975)

    PubMed  CAS  Google Scholar 

  • Lazarus, H.M., Owens, M.L., Hopfenbeck, A.: Allopurinol protection of hepatic nuclear function during hemorrhagic shock. Surg. Forum 25, 10–12 (1974)

    PubMed  CAS  Google Scholar 

  • Lefer, A.M., Daw, C.F., Berne, Q.M.: Cardiac and skeletal muscle metabolic energy stores in hemorrhagic shock. Amer. J. Physiol. 216, 483–486(1969)

    PubMed  CAS  Google Scholar 

  • Levin, N.W., Abrahams, O.L.: Allopurinol in patients with impaired renal function. Ann. rheum. Dis. 25, 681–687 (1966)

    PubMed  CAS  Google Scholar 

  • Levine, A.S., Sharp, H.L., Mitchell, J., Krewit, W., Nesbit, M.E.: Combination therapy with 6-mercaptopurine (NSC-755) and allopurinol (NSC-1390) during induction and maintenance of remission of acute leukemia in children. Cancer Chemother. Rep. 53, 53–57 (1969)

    PubMed  CAS  Google Scholar 

  • Lyon, G.M.: Allopurinol and cytotoxic agents. J. Amer. med. Ass. 228, 1371 (1974)

    Google Scholar 

  • Manzke, H., Dorner, K.: Effect of allopurinol on erythrocyte ATP and a 2,3-diphosphoglycerate levels and hemoglobin oxygen affinity in man. Arch. clin. Pharmacol. Ther. 3, 107 (1975)

    CAS  Google Scholar 

  • Massey, V., Komai, H., Palmer, G., Elion, G.B.: On the mechanism of inactivation of xanthine oxidase by allopurinol and other pyrazolo(3,4-d)pyrimidines. J. biol. Chem. 245, 2837–2844 (1970)

    PubMed  CAS  Google Scholar 

  • Massey, V., Komai, H., Palmer, G., Elion, G.B.: The existence of nonfunctional active sites in milk xanthine oxidase; reaction with functional active site inhibitors. Vitam. Horm. 28, 505–531 (1970 a)

    PubMed  CAS  Google Scholar 

  • Mazur, A., Carleton, A.: Hepatic xanthine oxidase and ferritin iron in the developing rat. Blood 26, 317–322(1965)

    PubMed  CAS  Google Scholar 

  • Mazur, A., Green, S., Saha, A., Carleton, A.: Mechanism of release of ferritin in vivo by xanthine oxidase. J. clin. Invest. 37, 1809–1817 (1958)

    PubMed  CAS  Google Scholar 

  • McCollister, R.J., Gilbert, W.R., Ashton, D.M., Wyngaarden, J.B.: Pseudofeedback inhibition of purine synthesis by 6-mercaptopurine ribonucleotide and other purine analogues. J. biol. Chem. 239, 1560–1563 (1964)

    PubMed  CAS  Google Scholar 

  • McDaniel, H.G., Podgainy, H., Bressler, R.: The metabolism of tolbutamide in rat liver. J. Pharmacol, exp. Ther. 167, 91–97 (1969)

    CAS  Google Scholar 

  • Miller, R.L., Adamczyk, D.L.: Inosine 5-monophosphate dehydrogenase from sarcoma 180 cells-substrate and inhibitory specificity. Biochem. Pharmacol. 25, 883–888 (1976)

    PubMed  CAS  Google Scholar 

  • Moon, R. J.: Tryptophan oxygenase and tryptophan metabolism in endotoxin-poisoned and allopurinol treated mice. Biochim. biophys. Acta (Amst.) 230, 342–348 (1971)

    CAS  Google Scholar 

  • Morita, M., Feller, D.R., Gillette, J.R.: Reduction of niridazole by rat liver xanthine oxidase. Biochem. Pharmacol. 20, 217–226 (1971)

    PubMed  CAS  Google Scholar 

  • Nelson, D. J.: Unpublished

    Google Scholar 

  • Nelson, D.J., Bugge, C.J.L., Krasny, H.C., Elion, G.B.: Formation of nucleotides of 6-14C oxipu-rinol in rat tissues and effects on uridine nucleotide pools. Biochem. Pharmacol. 22, 2003–2033 (1973)

    PubMed  CAS  Google Scholar 

  • Nelson, D.J., Elion, G.B.: Metabolism of [6-14C] allopurinol-lack of incorporation of allopurinol into nucleic acids. Biochem. Pharmacol. 24, 1235–1237 (1975)

    PubMed  CAS  Google Scholar 

  • Oster, K.A.: Treatment of angina pectoris according to a new theory of its origin. Cardiol. Dig. 3, 29–34(1968)

    Google Scholar 

  • Oster, K. A.: Plasmalogen diseases: a new concept of the etiology of the atherosclerotic process. Am. J. Clin. Res. 2, 30–35 (1971)

    Google Scholar 

  • Owens, M.L., Lazarus, H.M., Wolcott, M.W., Maxwell, J.G., Taylor, J.B.: Allopurinol and hypo-xanthine pretreatment of canine kidney donors. Transplantation 17, 224–227 (1974)

    Google Scholar 

  • Pak, C.Y.C., Arnold, L.H.: Heterogeneous nucleation of calcium oxalate by seeds of monosodium urate. Proc. Soc. exp. Biol. (N.Y.) 149, 930–932 (1975)

    CAS  Google Scholar 

  • Parker, J. C, Smith, E.E.: Effects of xanthine oxidase inhibition in cardiac arrest. Surgery 71, 339–344 (1972)

    PubMed  CAS  Google Scholar 

  • Payne, M.R., Dancis, J., Berman, P.H., Balis, M.E.: Inosine kinase in leucocytes of Lesch-Nyhan patients. Exp. Cell Res. 59, 489–490 (1970)

    PubMed  CAS  Google Scholar 

  • Pomales, R., Bieber, S., Friedman, R., Hitchings, G.H.: Augmentation of the incorporation of hypoxanthine into nucleic acids by the administration of an inhibitor of xanthine oxidase. Biochim. biophys. Acta (Amst.) 72, 119–120 (1963)

    CAS  Google Scholar 

  • Pomales, R., Elion, G.B., Hitchings, G.H.: Xanthine as a precursor of nucleic acid purines in the mouse. Biochim. biophys. Acta (Amst.) 95, 505–506 (1965)

    CAS  Google Scholar 

  • Powell, L.W.: Effects of allopurinol in iron storage in the rat. Ann. rheum. Dis. 25, 697–699 (1966)

    PubMed  CAS  Google Scholar 

  • Powell, L.W., Emmerson, B.T.: Haemosiderosis associated with xanthine oxidase inhibition. Lancet 1966 I, 239–240

    Google Scholar 

  • Prien, E.L., Prien, E.L.: Composition and structure of urinary stone. Amer. J. Med. 45, 654–672 (1968)

    PubMed  CAS  Google Scholar 

  • Ragab, A.H., Gilkerson, E., Myers, M.: The effect of 6-mercaptopurine and allopurinol on granulopoiesis. Cancer Res. 34, 2246–2249 (1974)

    PubMed  CAS  Google Scholar 

  • Rawlins, M.D., Smith, S. E.: Influence of allopurinol on drug metabolism in man. Brit. J. Pharmacol. 48, 693–698 (1973)

    CAS  Google Scholar 

  • Rodnan, G.P., Robin, J.A., Tolchin, S.F., Elion, G.B.: Allopurinol and gouty hyperuricemia. Efficacy of a single daily dose. J. Amer. med. Ass. 231, 1143–1147 (1975)

    CAS  Google Scholar 

  • Romas, N., Fingerhut, B., Feigelson, P., Veenema, R.: Apparent inhibition of bladder carcinogenesis in the rat by allopurinol. Proc. Amer. Ass. Cancer Res. 14, 95 (1973)

    Google Scholar 

  • Rosenbloom, F.M., Kelley, W.N., Miller, J.M., Seegmiller, J.E.: An enzymatic biochemical basis for variation in response to allopurinol. Arthr. and Rheum. 10, 307 (1967)

    Google Scholar 

  • Rundles, R.W.: Allopurinol in gouty nephropathy and renal dialysis. Ann. rheum. Dis. 25, 694–696 (1966)

    PubMed  CAS  Google Scholar 

  • Rundles, R.W.: Metabolic effects of allopurinol and alloxanthine. Ann. rheum. Dis. 25, 615–620 (1966a)

    PubMed  CAS  Google Scholar 

  • Rundles, R.W., Elion, G.B.: Unpublished Rundles, R.W., Elion, G.B., Hitchings, G.H.: Allopurinol in the treatment of gout and secondary hyperuricemia. Bull. rheum. Dis. 161, 400–403 (1966a)

    Google Scholar 

  • Rundles, R.W., Metz, E., Silberman, H.R.: Allopurinol in the treatment of gout. Ann. intern. Med. 64, 229–258 (1966)

    PubMed  CAS  Google Scholar 

  • Rundles, R.W., Wyngaarden, J.B., Hitchings, G.H., Elion, G.B.: Drugs and uric acid. Ann. Rev. Pharmacol. 9, 345–362 (1969)

    PubMed  CAS  Google Scholar 

  • Rundles, R.W., Wyngaarden, J.B., Hitchings, G.H., Elion, G.B., Silberman, H.R.: Effects of a xanthine oxidase inhibitor on thiopurine metabolism, hyperuricemia and gout. Trans. Ass. Amer. Phycns 76, 126–140 (1963)

    CAS  Google Scholar 

  • Ryckewaert, A.: Les indications du traitement de fond de la goutte. Cah. Med. 11, 669–673 (1970)

    PubMed  CAS  Google Scholar 

  • Scott, J.T. (Ed.): Symposium on allopurinol. Ann. rheum. Dis. 25(6), 599–718 (1966)

    Google Scholar 

  • Scott, J.T., Hall, A.P., Grahame, R.: Allopurinol in the treatment of gout. Brit. med. J. 1966 II, 321–327

    Google Scholar 

  • Seegmiller, J.E., Engelman, K., Klinenberg, J.R., Watts, R.W.E., Sjoerdsma, A.: Xanthine oxidase and iron. New Engl. J. Med. 270, 534–535 (1964)

    Google Scholar 

  • Seegmiller, J.E., Rosenbloom, F.M., Kelley, W.N.: Enzyme defect associated with a sex-linked human neurological disorder and excess purine synthesis. Science 155, 1682–1684 (1967)

    PubMed  CAS  Google Scholar 

  • Serre, H., Simon, L., Claustre, J.: Les urico-freinateurs dans le traitement de la goutte: à propos de 126 cas. Sem. Hôp. Paris 46, 3295–3301 (1970)

    PubMed  CAS  Google Scholar 

  • Shatney, C.H., MacCarter, D.J., Lillehei, R.C.: Effect of allopurinol, propanolol, and methylpred-nisolone on infarct size in experimental myocardial infarction. Amer. J. Cardiol. 37, 572–580 (1976)

    PubMed  CAS  Google Scholar 

  • Simmonds, H.A.: Urinary excretion of purines, pyrimidines, pyrazolopyrimidines in patients treated with allopurinol or oxipurinol. Clin. chim. Acta 23(2), 353–364 (1969)

    PubMed  CAS  Google Scholar 

  • Simmonds, H.A., Cadenhead, A., Cameron, J.S., Rising, T.J., Grahame, R., Dean, B.M.: Thiopurinol and purine metabolism. Metabolic and radioisotope studies. Ann. rheum. Dis. 33, 548–553 (1974)

    PubMed  CAS  Google Scholar 

  • Simmonds, H.A., Levin, B., Cameron, J.S.: Variations in allopurinol metabolism by xanthinuric subjects. Clin. Sci. molec. Med. 47, 173–178 (1974a)

    CAS  Google Scholar 

  • Simmonds, H.A., Van Acker, K.J., Cameron, J.S., McBurney, A., Snedden, W.: Purine excretion in complete adenine phosphoribosyltransferase deficiency: effect of diet and allopurinol therapy. J. clin. Chem. clin. Biochem. 14, 321 (1976)

    Google Scholar 

  • Sjoberg, K.-H.: Allopurinol therapy of gout with renal complications. Ann. rheum. Dis. 14, 688–690 (1966)

    Google Scholar 

  • Skipper, H.E, Robins, R.K., Thomson, J.R., Cheng, C.C., Brockman, R.W., Schabel, F.M. Jr.: Structure activity relationships observed on screening a series of pyrazalopyrimidines against experimental neoplasms. Cancer Res. 17, 579–596 (1957)

    PubMed  CAS  Google Scholar 

  • Smith, M.J.V.: Placebo vs. allopurinol for renal calculi. J. Urol. (in press) (1977)

    Google Scholar 

  • Smith, M.J.V., Boyce, W.H.: Allopurinol and urolithiasis. J. Urol. 102, 750–753 (1969)

    PubMed  CAS  Google Scholar 

  • Sorensen, L.: Seminars on the Lesch-Nyhan syndrome; management and treatment, discussion. Fed. Proc. 27, 1097 (1968)

    Google Scholar 

  • Spector, T.: Inhibition of urate production by allopurinol. Biochem. Pharmacol. 26, 355–358 (1977)

    PubMed  CAS  Google Scholar 

  • Spector, T., Johns, D.G.: Stoichiometric inhibition of reduced xanthine oxidase by hydroxypyrazolo[3,4-d]pyrimidines. J. biol. Chem. 245, 5079–5085 (1970)

    PubMed  CAS  Google Scholar 

  • Spector, T., Johns, D.G.: 4-Hydroxypyrazolo(3,4-d)pyrimidine as a substrate for xanthine oxidase: loss of conventional substrate activity with catalytic cycling of the enzyme. Biochem. Biophys. Res. Commun. 38, 583–589 (1970a)

    PubMed  CAS  Google Scholar 

  • Stanley, E.L.: Allopurinol, a generalized coronary vasodilator. Circulation 43–44, 229 (1971)

    Google Scholar 

  • Sweetman, L.: Urinary and cerebrospinal fluid oxypurine levels and allopurinol metabolism in the Lesch-Nyhan syndrome. Fed. Proc. 27, 1055–1058 (1968)

    PubMed  CAS  Google Scholar 

  • Tatsumi, K., Yamaguchi, T., Yoshimura, H.: Metabolsm of drugs. LXXX. The metabolic fate of nitrofuran derivatives. (3) Studies on enzymes in small intestinal mucosa of rat catalyzing degradation of nitrofuran derivatives. Chem. Pharm. Bull. (Tokyo) 21, 622–628 (1973)

    CAS  Google Scholar 

  • Tax, W. J.M., Veerkamp, J.H., Trijbels, F.J.M., Schretlen, E.D. A.M.: Mechanism of allopurinolmediated inhibition and stabilization of human orotate phosphoribosyltransferase and orotidine phosphate decarboxylase. Biochem. Pharmacol. 25, 2025–2032 (1976)

    PubMed  CAS  Google Scholar 

  • Tersigni, R., Toledo-Pereyra, L.H., Najarian, J.S.: Effects of methylprednisolone, glucagon, and allopurinol in the protection of pancreaticoduodenal allografts perfused for twenty-four hours. Surgery 78, 599–607 (1975)

    PubMed  CAS  Google Scholar 

  • Tjandramaga, T.B., Cucinell, S.A., Iscaili, Z.H., Perel, J.M., Dayton, P.G., Yii, T.-F., Gutman, A.B.: Observations on the disposition of probenecid in patients receiving allopurinol. Pharmacology 8(4–6), 259–272 (1972)

    PubMed  CAS  Google Scholar 

  • Toledo-Pereyra, L.H., Najarian, J.S.: Total recovery of ischemic kidneys treated with allopurinol before transplantation. Surg. Forum 24, 302–304 (1973)

    PubMed  CAS  Google Scholar 

  • Toledo-Pereyra, L.H., Najarian, J.S.: Allopurinol on renal preservation. Transplantation 20, 256 (1975)

    Google Scholar 

  • Toledo-Pereyra, L.H., Simmons, R.L., Najarian, J.S.: Protection of the ischemic liver by donor pretreatment before transplantation. Amer. J. Surg. 129, 513–517 (1975)

    PubMed  CAS  Google Scholar 

  • Toledo-Pereyra, L.H., Simmons, R.L., Olson, L.C., Najarian, J.S.: Clinical effect of allopurinol on preserved kidney. A randomized double blind study. Ann. Surg. 185, 128–131 (1977)

    PubMed  CAS  Google Scholar 

  • Udall, V.: Hepatic iron storage. Ann. Rheum. Dis. 25, 704 (1966)

    Google Scholar 

  • Utter, M.F.: Guanosine and inosine nucleotides. In: Boyer, P.D., Lardy, H., Myrbäck, K. (Eds.): The Enzymes, Vol. 2, pp. 75–88. New York: Academic Press 1960

    Google Scholar 

  • Vasko, K.A., De Wall, R.A., Riley, A.M.: Effect of allopurinol in renal ischemia. Surgery 71, 787–790 (1972)

    PubMed  CAS  Google Scholar 

  • Vesell, E.S., Passanti, G.T., Greene, F.E.: Impairment of drug metabolism in man by allopurinol and nortryptyline. New Engl. J. Med. 283, 1484–1488 (1970)

    PubMed  CAS  Google Scholar 

  • Vogler, W.R., Bain, J.A., Huguley, C.M., Palmer, H.G. Jr., Lowrey, M.E.: Metabolic and therapeutic effects of allopurinol in patients with leukemia and gout. Amer. J. Med. 40, 548–549 (1966)

    Google Scholar 

  • Walker, R.I., Horvath, W.L., Rule, W.S., Herion, J.C., Palmer, J.G.: The failure of allopurinol to enhance 6-mercaptopurine toxicity in rabbits. Cancer Res. 33, 755–758 (1973)

    PubMed  CAS  Google Scholar 

  • Wang, C.Y., Hayashida, S., Pamukcu, A.M., Brian, G.T.: Enhancing effect of allopurinol on the induction of bladder cancer in rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Cancer Res. 36, 1551–1555(1976)

    PubMed  CAS  Google Scholar 

  • Watts, R.W.E., Engelman, K., Klinenberg, J.R., Sjoerdsma, A., Seegmiller, J.E.: Enzyme defect in a case of xanthinuria. Nature (Lond.) 201, 395–396 (1964)

    CAS  Google Scholar 

  • Watts, R.W.E., Snedden, W., Parker, R.A.: A quantitative study of skeletal-muscle purines and pyrazolo(3,4-d)pyrimidines in gout patients treated with allopurinol. Clin. Sci. 41, 153–158 (1971)

    PubMed  CAS  Google Scholar 

  • Watts, R.W. E., Watts, J.E.M., Seegmiller, J.E.: Xanthine oxidase activity in human tissues and its inhibition by allopurinol (4-hydroxypyrazolo-[3,4-d]pyrimidine). J. Lab. clin. Invest. 66, 688–698 (1965)

    CAS  Google Scholar 

  • Way, J.L., Parks, R.E., Jr.: Enzymatic synthesis of 5′-phosphate nucleotides of purine analogs. J. biol. Chem. 231, 467–480 (1958)

    PubMed  CAS  Google Scholar 

  • Welch, R.M.: Drug-protein binding: A method for studying the interaction of drugs with bishydroxycoumarin (dicoumarol) in dogs. Ann. N.Y. Acad. Sci. 226, 259–266 (1973)

    PubMed  CAS  Google Scholar 

  • Wenzelides, K., Guski, H., Seidler, E., Meyer, R.: The influence of allopurinol on the alterations in the myocardium and the frequency of myocardial infarction in the hearts of rats under various experimental conditions. Dtsch. Gesundh.-Wes. 30, 183 (1975)

    Google Scholar 

  • Wenzelides, K., Meyer, R.: The influence of allopurinol upon the size of the experimental myocardial infarction in the rat. Dtsch. Gesundh.-Wes. 30, 229 (1975)

    Google Scholar 

  • Westerfeld, W.W., Richert, D.A., Bloom, R.J.: Inhibition of xanthine and succinic oxidases by carbonyl reagents. J. biol. Chem. 234, 1889–1896 (1959)

    PubMed  CAS  Google Scholar 

  • Wood, M.H., O’Sullivan, W. J., Wilson, M., Tiller, D.J.: Potentiation of an effect of allopurinol on pyrimidine metabolism by chlorothiazide in man. Clin. exp. Pharmacol. Physiol. 1, 53–58 (1974)

    PubMed  CAS  Google Scholar 

  • Wood, M.H., Sebel, E., O’Sullivan, W.J.: Allopurinol and thiazides. Lancet 1972 I, 751

    Google Scholar 

  • Worthy, T.E., Grobner,W., Kelley,W.N.: Hereditary orotic aciduria: evidence for structural gene mutation. Proc. nat. Acad. Sci. (Wash.) 71, 3031–3035 (1974)

    CAS  Google Scholar 

  • Yii, T.-F., Balis, M.E., Krenitsky, T.A., Dancis, J., Silvers, D.N., Elion, G.B., Gutman, A.B.: Rarity of X-linked partial hypoxanthine-guanine phosphoribosyltransferase deficiency in a large gouty population. Ann. intern. Med. 76, 255–264 (1972)

    Google Scholar 

  • Yu, T.-F., Gutman,A.B.: Study of the paradoxical effects of salicylate in low, intermediate, and high dosage on the renal mechanisms for excretion of urate in man. J. clin. Invest. 38, 1298–1315 (1959)

    PubMed  CAS  Google Scholar 

  • Yii, T.-F., Gutman, A.B.: Effect of allopurinol (4-hydroxypyrazolo(3,4-d)pyrimidine) on serum and urinary uric acid in primary and secondary gout. Amer. J. Med. 37, 885–898 (1964)

    Google Scholar 

  • Zuckerman, R., Drell, W., Levin, M.H.: Urinary purines in gout: effect of azaserine. Arthr. And Rheum. 2, 46–47 (1959)

    Google Scholar 

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Elion, G.B. (1978). Allopurinol and Other Inhibitors of Urate Synthesis. In: Kelley, W.N., Weiner, I.M. (eds) Uric Acid. Handbook of Experimental Pharmacology, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-66867-8_21

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