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OtherReview Article

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Pál Pacher, Alex Nivorozhkin and Csaba Szabó
Pharmacological Reviews March 2006, 58 (1) 87-114; DOI: https://doi.org/10.1124/pr.58.1.6
Pál Pacher
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Alex Nivorozhkin
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Csaba Szabó
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Abstract

The prototypical xanthine oxidase (XO) inhibitor allopurinol, has been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades. More recent data indicate that XO also plays an important role in various forms of ischemic and other types of tissue and vascular injuries, inflammatory diseases, and chronic heart failure. Allopurinol and its active metabolite oxypurinol showed considerable promise in the treatment of these conditions both in experimental animals and in small-scale human clinical trials. Although some of the beneficial effects of these compounds may be unrelated to the inhibition of the XO, the encouraging findings rekindled significant interest in the development of additional, novel series of XO inhibitors for various therapeutic indications. Here we present a critical overview of the effects of XO inhibitors in various pathophysiological conditions and also review the various emerging therapeutic strategies offered by this approach.

Footnotes

  • ↵1 Abbreviations: XO, xanthine oxidase; 6-MP, 6-mercaptopurine; XDH, xanthine dehydrogenase; XOR, xanthine oxidoreductase; NO, nitric oxide; ROS, reactive oxygen species; UW, University of Wisconsin; CHF, chronic heart failure; NOS, nitric-oxide synthase; nNOS, neuronal NOS; SHR, spontaneously hypertensive rat; AHPP, 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine; BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one; Y-700, 1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid.

  • This work was supported by Intramural Research of National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (to P.P.).

  • Article, publication date, and citation information can be found at http://pharmrev.aspetjournals.org.

  • doi:10.1124/pr.58.1.6.

  • The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 58 (1)
Pharmacological Reviews
Vol. 58, Issue 1
1 Mar 2006
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OtherReview Article

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Pál Pacher, Alex Nivorozhkin and Csaba Szabó
Pharmacological Reviews March 1, 2006, 58 (1) 87-114; DOI: https://doi.org/10.1124/pr.58.1.6

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OtherReview Article

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Pál Pacher, Alex Nivorozhkin and Csaba Szabó
Pharmacological Reviews March 1, 2006, 58 (1) 87-114; DOI: https://doi.org/10.1124/pr.58.1.6
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  • Article
    • Abstract
    • I. Introduction, Historical Background
    • II. The Structure and Molecular Biochemistry of Xanthine Oxidoreductase
    • III. Xanthine Oxidase-Derived Superoxide as Part of a Complex Oxidant and Antioxidant System
    • IV. Xanthine Oxidase Inhibitors
    • V. Therapeutic Areas Relevant for Xanthine Oxidase Inhibitors
    • VI. Future Development of Xanthine Oxidase Inhibitors
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