Oxipurinol

Last updated
Oxipurinol
Oxypurinol.svg
Names
Preferred IUPAC name
1H-pyrazolo[3,4-d]pyrimidine-4,6(2H,5H)-dione
Other names
2,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine-4,6-dione
Alloxanthine
Identifiers
3D model (JSmol)
139956
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.017.792 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 219-570-9
KEGG
MeSH Oxypurinol
PubChem CID
UNII
  • InChI=1S/C5H4N4O2/c10-4-2-1-6-9-3(2)7-5(11)8-4/h1H,(H3,6,7,8,9,10,11)
    Key: HXNFUBHNUDHIGC-UHFFFAOYSA-N
  • O=C1NC(=O)C2=CNNC2=N1
Properties
C5H4N4O2
Molar mass 152.11086
Appearancewhite crystals
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Oxipurinol (INN, or oxypurinol USAN) is an inhibitor of xanthine oxidase. [1] It is an active metabolite of allopurinol and it is cleared renally. [2] In cases of renal disease, this metabolite will accumulate to toxic levels. By inhibiting xanthine oxidase, it reduces uric acid production. High serum uric acid levels may result in gout, kidney stones, and other medical conditions.

Related Research Articles

Uric acid The end product of nucleic acid degradation

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

Gout Medical condition that results in recurrent pain and swelling of joints

Gout is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected in about half of cases. It may also result in tophi, kidney stones, or kidney damage.

Xanthine oxidase

Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, including humans.

Allopurinol

Allopurinol, sold under the brand name Zyloprim among others, is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth or injected into a vein.

Hyperuricemia

Hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Kidney disease Damage to or disease of a kidney

Kidney disease, or renal disease, also known as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

Tumor lysis syndrome is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer, where large amounts of tumor cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias. In oncology and hematology, this is a potentially fatal complication, and patients at increased risk for TLS should be closely monitored before, during, and after their course of chemotherapy.

Urate oxidase

The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:

Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.

Hypouricemia

Hypouricemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L (6 mg/dL) for women and 619 micromol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

Febuxostat

Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth.

Hyperuricosuria

Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. For men this is at a rate greater than 800 mg/day, and for women, 750 mg/day. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia. Notable indirect causes include uricosuric drugs, rapid breakdown of bodily tissues containing large quantities of DNA and RNA, and a diet high in purine.

SLC22A12

Solute carrier family 22, member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.

Benzbromarone

Benzbromarone is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone.

<i>Cinnamomum osmophloeum</i> Species of tree

Cinnamomum osmophloeum, commonly known as pseudocinnamomum or indigenous cinnamon, is a medium-sized evergreen tree in the genus Cinnamomum. It is native to broad-leaved forests of central and northern Taiwan.

Tisopurine

Tisopurine is a drug used in the treatment of gout in some countries. It reduces uric acid production through inhibiting an early stage in its production.

A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of hyperuricemia and related medical conditions including gout. Xanthine oxidase inhibitors are being investigated for management of reperfusion injury.

Sān miào wán is a traditional Chinese medicine consisting of three components:

Lesinurad

Lesinurad is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is only recommended together with either allopurinol or febuxostat when these medications are not sufficient.

References

  1. Stocker, Sophie L; McLachlan, Andrew J; Savic, Radojka M; Kirkpatrick, Carl M; Graham, Garry G; Williams, Kenneth M; Day, Richard O (2012). "The pharmacokinetics of oxypurinol in people with gout". British Journal of Clinical Pharmacology. 74 (3): 477–489. doi:10.1111/j.1365-2125.2012.04207.x. PMC   3477349 . PMID   22300439.
  2. Elion, Gertrude B; Yü, Ts'ai-Fan; Gutman, Alexander B; Hitchings, George H (1968). "Renal clearance of oxipurinol, the chief metabolite of allopurinol". The American Journal of Medicine. 45 (1): 69–77. doi:10.1016/0002-9343(68)90008-9. PMID   5658870.