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

Details

Stereochemistry ACHIRAL
Molecular Formula C14H11Cl2NO2
Molecular Weight 296.149
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DICLOFENAC

SMILES

OC(=O)CC1=CC=CC=C1NC2=C(Cl)C=CC=C2Cl

InChI

InChIKey=DCOPUUMXTXDBNB-UHFFFAOYSA-N
InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)

HIDE SMILES / InChI

Molecular Formula C14H11Cl2NO2
Molecular Weight 296.149
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. In addition diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel mechanisms of action may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. The drug's likely impact on the Asian vulture population was widely reported. The dramatic mortality was attributed largely to renal failure caused by exposure to diclofenac in livestock carcasses on which the birds fed. Although not the most endearing species, vultures are important environmental scavengers and, since veterinary use of diclofenac was stopped in the region in 2006, the decline in vulture numbers has slowed.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.037 µM [IC50]
0.97 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DICLOFENAC SODIUM
Primary
DICLOFENAC SODIUM
PubMed

PubMed

TitleDatePubMed
Nimesulide, a balanced drug for the treatment of osteoarthritis.
2001
Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.
2001
Celecoxib versus diclofenac in the management of osteoarthritis of the knee.
2001
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.
2001
Review: uveitis and immunosuppressive drugs.
2001 Apr
Cataflam-induced esophageal ulceration.
2001 Apr
Anti-inflammatory drugs. IX. Hydrated diethylammonium (2-(2,6-dichlorophenylamino)phenyl)acetate (HDEA.D.H2O).
2001 Apr
Efficacy of peripheral morphine analgesia in inflamed, non-inflamed and perineural tissue of dental surgery patients.
2001 Apr
Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.
2001 Apr
The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use.
2001 Apr
Tramadol vs. diclofenac for posttonsillectomy analgesia.
2001 Apr
Equivalence of generic and brand-name ophthalmic products.
2001 Apr 1
HPLC evaluation of diclofenac in transdermal therapeutic preparations.
2001 Apr 17
Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.
2001 Apr 28
Inhibition of COX in ocular tissues: an in vitro model to identify selective COX-2 inhibitors.
2001 Feb
Comparative study of diclofenac sodium and paracetamol for treatment of pain after adenotonsillectomy in children.
2001 Feb
Diclofenac-induced gastric mucosal fluorescence in rats.
2001 Feb
When should diclofenac be given in ambulatory surgery: preoperatively or postoperatively?
2001 Feb
Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo.
2001 Feb
Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia.
2001 Feb
Thermographic imaging of postoperative inflammation modified by anti-inflammatory pretreatment.
2001 Feb
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.
2001 Feb 23
A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines.
2001 Jan
Truth and consequences.
2001 Jan
Truth and consequences.
2001 Jan
Renal colic and recurrent urinary calculi. Management and prevention.
2001 Jan
Inadvertent diclofenac rechallenge from generic and non-generic prescribing, leading to liver transplantation for fulminant liver failure.
2001 Jan
Inhibition of the nitrosothiol production of cultured osteoarthritic chondrocytes by rhein, cortisol and diclofenac.
2001 Jan
High-dose intrathecal diamorphine for analgesia after Caesarean section.
2001 Jan
Effects of diclofenac in the rat tail ischaemia--reperfusion injury model of acute hyperalgesia.
2001 Jan
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.
2001 Jan 10
Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS).
2001 Jan 29
[Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in the French Pharmacovigilance Database].
2001 Jan-Feb
Is diclofenac a valuable CYP2C9 probe in humans?
2001 Jan-Feb
Analgesic effect of epidural neostigmine after abdominal hysterectomy.
2001 Mar
Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy.
2001 Mar
Docetaxel extravasation.
2001 Mar
[Effect of tobramycin with topical diclofenac on arachidonic acid in endotoxin-induced uveitis].
2001 Mar
Physical incompatibility between atracurium and intravenous diclofenac.
2001 Mar
Cytochrome P450 expression and related metabolism in human buccal mucosa.
2001 Mar
Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.
2001 Mar
In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs.
2001 Mar
Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/l level in surface and waste water.
2001 Mar 16
Use of ion-exchange resins to prepare 100 microm-sized microcapsules with prolonged drug-release by the Wurster process.
2001 Mar 23
Decreased flow-dependent dilation in carotid arteries of tissue kallikrein-knockout mice.
2001 Mar 30
Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs.
2001 May
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
2001 May
Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process.
2001 May
Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac.
2001 May
Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity.
2001 May
Patents

Sample Use Guides

In Vivo Use Guide
For topical dosage form (gel): For actinic keratosis using Solaraze® 3% gel: Adults—Apply to affected skin area two times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis of the hands, elbows, or wrists using Voltaren® 1% gel: Adults—Apply 2 grams to the affected skin areas four times a day (a total of 8 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For osteoarthritis of the knees, ankles, or feet using Voltaren® 1% gel: Adults—Apply 4 grams to the affected skin areas four times a day (a total of 16 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For topical dosage form (solution): For osteoarthritis of the knee: Adults—40 drops (10 drops at a time) on each affected knee four times a day. Children—Use and dose must be determined by your doctor. For transdermal dosage form (skin patch): For acute pain: Adults—One patch applied to the painful area two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (capsules): For acute pain: Adults—18 or 35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For oral dosage forms (delayed-release tablets, enteric-coated tablets): For ankylosing spondylitis: Adults—25 milligrams (mg) four times a day, with an extra 25 mg dose at bedtime if necessary. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—50 milligrams (mg) two or three times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (immediate-release tablets): For osteoarthritis: Adults—50 milligrams (mg) two or three times a day. Children—Use and dose must be determined by your doctor. For pain or menstrual cramps: Adults—50 milligrams (mg) three times a day. Your doctor may direct you to take 100 mg for the first dose only. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (solution): For migraine headaches: Adults—One packet (50 milligrams) as a single, one time dose. Children—Use and dose must be determined by your doctor.
Route of Administration: topical, oral
In Vitro Use Guide
Acute (24 h) diclofenac toxicity in a range of (10-1000 μM) concentrations was assesed in primary human hepatocytes. The chronic (9 repeated doses) toxicity at one clinically relevant and another higher concentration (6.4 and 100 μM) was also tested. Acute 24 h assessment revealed toxicity only for the highest tested concentration (1 mM). Upon repeated dose exposure, toxic effects were observed even at a low, clinically relevant concentration (6.4 μM).
Substance Class Chemical
Created
by admin
on Tue Oct 22 00:33:25 UTC 2019
Edited
by admin
on Tue Oct 22 00:33:25 UTC 2019
Record UNII
144O8QL0L1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DICLOFENAC
HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
DICLOFENAC [MI]
Common Name English
DICLOFENAC [VANDF]
Common Name English
DICLOFENAC FREE ACID
Common Name English
ACECLOFENAC IMPURITY A [EP]
Common Name English
DICLOFENAC [HSDB]
Common Name English
DICLOFENAC [INN]
Common Name English
(2-((2,6-DICHLOROPHENYL)AMINO)PHENYL)ACETIC ACID
Systematic Name English
DICLOFENAC [MART.]
Common Name English
BENZENEACETIC ACID, 2-((2,6-DICHLOROPHENYL)AMINO)-
Common Name English
DICLOFENAC [USAN]
Common Name English
DICLOFENAC [WHO-DD]
Common Name English
(O-(2,6-DICHLOROANILINO)PHENYL)ACETIC ACID
Common Name English
Classification Tree Code System Code
WHO-ATC M01AB05
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-ATC S01BC03
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-ATC S01CC01
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
CFR 21 CFR 524.590
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-ATC D11AX18
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-VATC QD11AX18
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
NDF-RT N0000175722
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-ATC M01AB55
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
LIVERTOX 297
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-VATC QM02AA15
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-VATC QS01CC01
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-ATC M02AA15
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-VATC QM01AB05
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
WHO-VATC QS01BC03
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
NCI_THESAURUS C1323
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
Code System Code Type Description
DRUG BANK
DB00586
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
HSDB
15307-86-5
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
LactMed
15307-86-5
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
RXCUI
3355
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY RxNorm
INN
3270
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
MESH
D004008
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
EPA CompTox
15307-86-5
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
CAS
15307-86-5
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
ChEMBL
CHEMBL139
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
WIKIPEDIA
DICLOFENAC
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
MERCK INDEX
M4361
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY Merck Index
EVMPD
SUB07092MIG
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
ECHA (EC/EINECS)
239-348-5
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
PUBCHEM
3033
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
IUPHAR
2714
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
NCI_THESAURUS
C28985
Created by admin on Tue Oct 22 00:33:25 UTC 2019 , Edited by admin on Tue Oct 22 00:33:25 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
POTENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
POTENT
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
MINOR
METABOLITE -> PARENT
CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac
MINOR
METABOLITE -> PARENT
CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac
MINOR
PRODRUG -> METABOLITE ACTIVE
METABOLITE -> PARENT
METABOLITE LESS ACTIVE -> PARENT
The formation of 4'-hydroxy-diclofenac is primarily mediated by CYP2C9
MAJOR
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY