| Drug ID: | D006 |
| Drug Name: | Allopurinol |
| Synonyms: |
1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one; 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one; 1H-Pyrazolo(3,4-d)pyrimidin-4-ol; 4-HPP; 4-Hydroxy-1H-pyrazolo(3,4-d)pyrimidine; 4-Hydroxy-3,4-pyrazolopyrimidine; 4-Hydroxypyrazolo(3,4-d)pyrimidine; 4-Hydroxypyrazolopyrimidine; 4-Hydroxypyrazolyl(3,4-d)pyrimidine; 4'-Hydroxypyrazolol(3,4-d)pyrimidine; 4H-Pyrazolo(3,4-d)pyrimidin-4-one; Allopurinol
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| Type: | Chemical drug |
| DrugBank ID: |
DB00437
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| DrugBank Description: |
Gout is a disease that occurs by the deposition of monosodium urate crystals (MSU) in body tissues, especially around joints . This disease has been well-documented in historical medical records and appears in the biographies of several prominent, historically recognized individuals .
Allopurinol is a xanthine oxidase enzyme inhibitor that is considered to be one of the most effective drugs used to decrease urate levels and is frequently used in the treatment of chronic gout . It was initially approved by the FDA in 1966 and is now formulated by several manufacturers .
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| PubChem ID: |
135401907
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| CasNo: |
315-30-0
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| Repositioning for NAFLD: |
Yes
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| SMILES: |
O=c1c2c(nc[nH]1)[nH]nc2
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| Structure: |
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| InChiKey: |
OFCNXPDARWKPPY-UHFFFAOYSA-N
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| Molecular Weight: |
136.114
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| DrugBank Targets: |
Xanthine dehydrogenase/oxidase inhibitor
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| DrugBank MoA: |
Allopurinol is a structural analog of the natural purine base, hypoxanthine. After ingestion, allopurinol is metabolized to its active metabolite, oxypurinol (_alloxanthine_) in the liver , which acts as an inhibitor of xanthine oxidase enzyme .
Allopurinol and its active metabolite inhibit xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Inhibition of this enzyme is responsible for the effects of allopurinol. This drug increases the reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis by a process that involves the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). This process results in an increased nucleotide concentration, which causes feedback inhibition of de novo purine synthesis. The end result is decreased urine and serum uric acid concentrations , which decreases the incidence of gout symptoms.
Accompanying the reduction of serum uric acid by allopurinol is an increase in the serum and urine concentrations of hypoxanthine and xanthine (due to inhibition of xanthine oxidase). In the absence of allopurinol, regular urinary excretion of oxypurines almost entirely occurs in the form of uric acid. After the ingestion of allopurinol, the contents of excreted urine are hypoxanthine, xanthine, and uric acid. Because each substance has its own individual solubility, the concentration of uric acid in plasma is decreased without exposing the renal tissues to a high load of uric acid, thereby decreasing the risk of crystalluria. By lowering the uric acid concentration in the plasma below its limits of solubility, allopurinol encourages the dissolution of gout tophi. Although the levels of hypoxanthine and xanthine are found to be increased after allopurinol ingestion, the risk of deposition in renal tissues is less than that of uric acid, as they become more soluble and are rapidly excreted by the kidney .
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| DrugBank Pharmacology: |
Allopurinol decreases the production of uric acid by stopping the biochemical reactions that precede its formation . This process decreases urate and relieves the symptoms of gout, which may include painful tophi, joint pain, inflammation, redness, decreased range of motion, and swelling .
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| DrugBank Indication: |
Allopurinol is indicated in :
1) the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy).
2) the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Treatment with allopurinol should be discontinued when the potential for overproduction of uric acid is no longer present.
3) the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks.
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| Targets: |
XO inhibitor
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| Therapeutic Category: |
--
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| Clinical Trial Progress: |
Phase 3 on-going (IRCT20180404039187N2)
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| Latest Progress: |
Under clinical trials
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