U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C5H4N4O
Molecular Weight 136.1115
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALLOPURINOL

SMILES

O=C1N=CNC2=C1C=NN2

InChI

InChIKey=OFCNXPDARWKPPY-UHFFFAOYSA-N
InChI=1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10)

HIDE SMILES / InChI

Molecular Formula C5H4N4O
Molecular Weight 136.1115
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Allopurinol is a xanthine oxidase inhibitor used to decrease high blood uric acid levels. Allopurinol is specifically used to prevent gout, prevent specific types of kidney stones, and for the high uric acid levels that can occur with chemotherapy. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analog of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. Allopurinol is metabolized to the corresponding xanthine analog, oxypurinol (Allopurinol), which also is an inhibitor of xanthine oxidase. Allopurinol is taken by mouth or injected into a vein. Common side effects, when used by mouth, include itchiness and rash. Common side effects when used by injection include vomiting and kidney problems.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
2.9 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ZYLOPRIM
Secondary
ZYLOPRIM
Primary
ZYLOPRIM

Cmax

ValueDoseCo-administeredAnalytePopulation
3 μg/mL
300 mg single, oral
ALLOPURINOL plasma
Homo sapiens
0.64 μg/mL
200 mg single, oral
ALLOPURINOL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
4.46 μg × h/mL
200 mg single, oral
ALLOPURINOL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
300 mg single, oral
ALLOPURINOL plasma
Homo sapiens

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

PubMed

Sample Use Guides

In Vivo Use Guide
The dosage of Allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg per day for patients with mild gout and 400 to 600 mg per day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily.
Route of Administration: Other
In Vitro Use Guide
Primary rat osteoblast cells were obtained from 2-day-old neonatal Sprague-Dawley rats. Following isolation, cells were resuspended in Dulbecco's Modified Essential Medium, supplemented with 10% foetal calf serum (FCS), 2 mM L-glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin and 0.25 mg/ml amphotericin (complete mixture abbreviated to DMEM). Cells were cultured for 2–4 days in a humidified atmosphere of 5% CO2–95% air at 37 °C in 75 cm2 flasks until confluent. Upon confluence, cells were sub-cultured into 24- well trays in DMEM supplemented with 2 mM β-glycerophosphate, 50 μg/ml ascorbic acid and 10 nM dexamethasone (supplemented DMEM), with half medium changes every 3 days. Osteoblasts were cultured in the presence of allopurinol and oxypurinol (1 nM–10 mM) to determine the effect on cell proliferation, differentiation, function and gene expression. For the bone formation experiments, cells were also treated with febuxostat and, as a positive control of an anabolic agent, BMP2 (0.1 mM). Unless stated, experiments were carried out at 2 time points during the osteoblast culture; day 7, which represents differentiating osteoblasts, and day 14 (mature, bone forming osteoblasts). All experiments were carefully pH-controlled because bone mineralisation is extremely sensitive to inhibition by acidosis
Substance Class Chemical
Record UNII
63CZ7GJN5I
Record Status Validated (UNII)
Record Version