General
Preferred name
INDOMETHACIN
Synonyms
Indometacin ()
Indocin ()
Indometacine ()
Indomethacine ()
Indomethacin (sodium hydrate) ()
INDOMETHACIN SODIUM ()
Indometacin (sodium hydrate) ()
Indomethacin (NSC-77541) ()
Indometacin Sodium ()
Indometacin,NSC-77541 ()
Artracin sr ()
Indocin sr ()
Indomax-25 ()
Indo-lemmon ()
Indoptol ()
Tivorbex ()
INDOMETACIN FARNESIL ()
Indo-paed ()
NSC-757061 ()
Reumacide ()
Flexin-75 continus ()
Indomod ()
Mobilan ()
Slo-indo ()
Rimacid ()
Berlind 75 ret ()
Durametacin ()
Rheumacin la ()
Indoderm ()
Flexin-50 continus ()
Maximet sr ()
Flexin-25 continus ()
Indometacinum ()
Indotard mr 75 ()
Aconip ()
Pardelprin mr ()
Indolar ()
Indoflex ()
Ledmecin ()
Indomax-75 sr ()
Indolar sr ()
NSC-77541 ()
Imbrilon ()
Indocid ret ()
Artracin ()
Indocid-r ()
Indomethacin sodium salt trihydrate ()
Indometacin sodium hydrate ()
Sodium indomethacin ()
Indomethacin sodium trihydrate ()
Sodium indomethacin trihydrate ()
Indomethacin sodium anhydrous ()
Indometacin sodium trihydrate ()
Indometacin sodium ()
Indomethacin-d4 ()
P&D ID
PD002292
CAS
53-86-1
37242-43-6
74252-25-8
28751-45-3
87377-08-0
Tags
obsolete probe
probe
natural product
drug
available
Approved by
FDA
First approval
1965
1985
Drug Status
investigational
approved
withdrawn
Drug indication
Rheumatoid arthritis
Anti-Inflammatory
Max Phase
Phase 4
Probe info
Probe type
calculated probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
7
No orthogonal probes found
Similar probes
2
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.[A177871,L6778]; ; Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.[F4600]
ROE
Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis [A177949]. The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.[A177949]; ; About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).[L6778]
TOXICITY
Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice.[MSDS] The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.[L6778] ; ; Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage.[L6778] The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful.[L6778]
METABOLISM
Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation.[A177949] O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity.[A177949,L6778] Unconjugated metabolites are also detected in the plasma.[L6778] Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism.[A177949]
ABSORPTION
Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent.[A177871] Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration [A177871] and about 90% of the dose is absorbed within 4 hours.[L6778] The bioavailability is about 80-90% following rectal administration.[A177901]; ; The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state.[A177901] Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively.[A177901] With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.[L6778]
HALF-LIFE
Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase.[A177949] Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.[A177874,A177949]; ; The mean half-life of oral indomethacin is estimated to be about 4.5 hours.[L6778] The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.[F4600]
DESCPRITION
A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.
DESCRIPTION
Indomethacin is a non-selective cyclooxygenase (COX) inhibitor belonging to the nonsteroidal anti-inflammatory drug (NSAID) family.
(GtoPdb)
MOA
Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme, or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation.[A177871] Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2.[A177871] COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the active site of the enzyme and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.; ; The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis.[L6778] At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth.[A177880] Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus.[A177880] By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.[F4600]
PHARMACODYNAMICS
Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.[L6778] Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength.[L6778] In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.[L6778]; ; In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment.[L6778] The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity.[A177871] There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.[A177871]
DESCRIPTION
Anti-inflammatory; antipyretic and analgesic; blocks prostaglandin biosynthesis by inhibiting prostaglandin cyclooxygenase
(LOPAC library)
DESCRIPTION
Cyclooxygenase inhibitor (COX-1 > COX-2)
(Tocriscreen Total)
DESCRIPTION
E2 ubiquitin (Ub) conjugating enzymes inhibitor
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
10
Organisms
5
Compound Sets
38
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
Ki Database
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Obsolete Compounds
Other bioactive compounds
Prestwick Chemical Library
Probe Miner (suitable probes)
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Total
Withdrawn 2.0
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
72
Molecular Weight
357.08
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
1
Rotatable Bonds
4
Ring Count
3
Aromatic Ring Count
3
cLogP
3.93
TPSA
68.53
Fraction CSP3
0.16
Chiral centers
0.0
Largest ring
6.0
QED
0.77
Structural alerts
1
historic compounds (Chemical Probes.org)
Obsolete
Related compounds
Custom attributes
(extracted from source data)
Selectivity
COX
Pathway
Immunology/Inflammation
Metabolism
Neuroscience
Anti-infection
Target
COX-1
COX-2
PDE2
PLA2
GLO1, PLA2G2A, PPARA, PPARG, PTGDR2, PTGR2, PTGS1, PTGS2, SLC46A1
COX inhibitor
antibiotic
Bacterial
Influenza Virus
Primary Target
Cyclooxygenases
MOA
Inhibitor
Cyclooxygenase-3 Inhibitors
Cyclooxygenase-1 Inhibitors
Cyclooxygenase-2 Inhibitors
Non-Steroidal Antiinflammatory Drugs
cyclooxygenase inhibitor
Member status
member
Indication
rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, bursitis, tendinitis
Disease Area
rheumatology, orthopedics
ATC
M01AB51
M02AA23
C01EB03
S01BC01
M01AB01
Toxicity type
multiple
gastrointestinal
Therapeutic Class
Antiinflammatory Agents
Source data
