Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol.
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.
Pacher
Pál
P
Laboratory of Physiological Studies, National Institute on Alcohol Aabuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane MSC 9413, Room 2N-17, Bethesda, Maryland 20892-9413, USA. pacher@mail.nih.gov
Nivorozhkin
Alex
A
Szabó
Csaba
C
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D015427:Reperfusion Injury / Q000188:drug therapy; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004791:Enzyme Inhibitors; D013481:Superoxides; D000493:Allopurinol; D014969:Xanthine Oxidase