Diclofenac (T3D4729)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (8)XML
Targets (8)
Record Information
Version2.0
Creation Date2014-09-11 05:13:44 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4729
Identification
Common NameDiclofenac
ClassSmall Molecule
DescriptionA non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
Compound Type
  • Amine
  • Anti-Inflammatory Agent, Non-Steroidal
  • Cyclooxygenase Inhibitor
  • Drug
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2-((2,6-Dichlorophenyl)amino)benzeneacetic acid
Aclonac
Allvoran
CAMBIA
Cataflam
Diclofenac acid
Diclofenaco
Diclofenacum
Dyloject
Ecofenac
Effekton
Flector
ISV-205
Nu-Diclo
Pennsaid
Primofenac
Prophenatin
Rhumalgan
Solaraze
Voltaren
Voltaren Emulgel
Voltarol
Zipsor
Zorvolex
[2-(2,6-Dichloroanilino)phenyl]acetic acid
Chemical FormulaC14H11Cl2NO2
Average Molecular Mass296.149 g/mol
Monoisotopic Mass295.017 g/mol
CAS Registry Number15307-86-5
IUPAC Name2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
Traditional Namediclofenac
SMILESOC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
InChI IdentifierInChI=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)
InChI KeyInChIKey=DCOPUUMXTXDBNB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dichlorobenzenes. Dichlorobenzenes are compounds containing a benzene with exactly two chlorine atoms attached to it.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentDichlorobenzenes
Alternative Parents
Substituents
  • Aniline or substituted anilines
  • 1,3-dichlorobenzene
  • Aryl chloride
  • Aryl halide
  • Amino acid or derivatives
  • Amino acid
  • Carboxylic acid derivative
  • Carboxylic acid
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Amine
  • Organochloride
  • Organohalogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point283-285°C
Boiling PointNot Available
Solubility2.37 mg/L (at 25°C)
LogP4.51
Predicted Properties
PropertyValueSource
Water Solubility0.0045 g/LALOGPS
logP4.98ALOGPS
logP4.26ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)4ChemAxon
pKa (Strongest Basic)-2.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.33 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity75.46 m³·mol⁻¹ChemAxon
Polarizability27.93 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03xv-3390000000-cd724f772f8ff36488562017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03xv-3390000000-cd724f772f8ff36488562018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-4290000000-1eb3d1011ce45deff9622017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0udi-5090000000-00fc73f6f5cfbb7052d02017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-1d8a04523a99bbdd0f792017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-55cf6c5663edc2bce2af2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-0257da659c18c3020ebe2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0w29-0090000000-eba79744370d30689f452017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03fr-0890000000-0870dbb742038ce60ba12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0900000000-a9b9817f70b72a3271692017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-58aba74cf5c165b0b3e52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-380ce6ec03fa880c2fee2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0w29-0090000000-1c764b23643b9731a5a22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0ik9-0290000000-5d59b6e5d4465a9e64932017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0900000000-483b1ac79bbfb8f591c22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0fb9-0950000000-4192d5344ed223d4bfd62017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0090000000-1d8a04523a99bbdd0f792017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-0090000000-d28bb6688b1bce51bfce2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0udi-0090000000-33332a8dbce37d5ad7592017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0udi-1490000000-f1c9ca0a1b924dba188e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-004i-4910000000-4c58f3f969da3d86e23c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00or-7900000000-3b2e03ec45a0b642cb4d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0udi-0390000000-247401e4df8c88d9f2602017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002b-0090000000-a3ff3ed470584d6946662016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0090000000-29ed9f5d1fb4bcf6262b2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ug0-4290000000-a381ef55b23a6901b44a2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0f6x-0090000000-00e8c59bbd02e8ef68e72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6x-0090000000-dae419eef17327b624d52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0kc6-4390000000-a037e01b7793bd48c1d52016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-03xv-1290000000-8fb3ce6f68fc69b5218e2014-09-20View Spectrum
Toxicity Profile
Route of ExposureCompletely absorbed from the gastrointestinal tract.
Mechanism of ToxicityThe antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of diclofenac. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
MetabolismHepatic. Route of Elimination: Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Half Life: 2 hours
Toxicity ValuesLD50=390mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00586
HMDB IDNot Available
PubChem Compound ID3033
ChEMBL IDCHEMBL139
ChemSpider ID2925
KEGG IDC01690
UniProt IDNot Available
OMIM ID
ChEBI ID4507
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDiclofenac
References
Synthesis Reference

Takuzo Kamishita, “Gel preparations for topical application of diclofenac sodium.” U.S. Patent US4670254, issued October, 1983.

MSDST3D4729.pdf
General References
  1. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. [16740558 ]
  2. Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S: Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89. [16645966 ]
  3. FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. [11496855 ]
  4. Graham DJ: COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13):1653-6. Epub 2006 Sep 12. [16968830 ]
  5. Brater DC: Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15-20; discussion S21-3. [11992745 ]
  6. Gan TJ: Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010 Jul;26(7):1715-31. doi: 10.1185/03007995.2010.486301. [20470236 ]
  7. Sigma Aldrich [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Prostaglandin G/H synthase 1
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5. [12414874 ]
  2. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [12534640 ]
  3. Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S: Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003 May;120(5):880-90. [12713596 ]
  4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [12852704 ]
  5. Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K: Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35. [12966366 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
2. Prostaglandin G/H synthase 2
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [12534640 ]
  2. Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br J Dermatol. 2003 Feb;148(2):211-23. [12588370 ]
  3. Beubler E: [Pharmacology of cyclooxygenase 2 inhibition]. Wien Med Wochenschr. 2003;153(5-6):95-9. [12705061 ]
  4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [12852704 ]
  5. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ: A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. [12925531 ]
Target Details
3. Arachidonate 5-lipoxygenase
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
References
  1. Charlier C, Michaux C: Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003 Jul-Aug;38(7-8):645-59. [12932896 ]
  2. Kudo C, Kori M, Matsuzaki K, Yamai K, Nakajima A, Shibuya A, Niwa H, Kamisaki Y, Wada K: Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem Pharmacol. 2003 Jul 15;66(2):289-95. [12826271 ]
  3. Whittle BJ: Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr Opin Pharmacol. 2004 Dec;4(6):538-45. [15525540 ]
Target Details
4. Phospholipase A2, membrane associated
General Function:
Phospholipid binding
Specific Function:
Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
Gene Name:
PLA2G2A
Uniprot ID:
P14555
Molecular Weight:
16082.525 Da
References
  1. Madanick RD, O'Loughlin CJ, Barkin JS: Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Dig Dis Sci. 2005 May;50(5):879-81. [15906762 ]
  2. Singh N, Jabeen T, Sharma S, Somvanshi RK, Dey S, Srinivasan A, Singh TP: Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A2: structure of the complex formed between phospholipase A2 and diclofenac at 2.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):410-6. Epub 2006 Mar 18. [16552142 ]
  3. Makela A, Kuusi T, Schroder T: Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997 Aug;57(5):401-7. [9279965 ]
Target Details
5. Sodium channel protein type 4 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Yang YC, Kuo CC: An inactivation stabilizer of the Na+ channel acts as an opportunistic pore blocker modulated by external Na+. J Gen Physiol. 2005 May;125(5):465-81. Epub 2005 Apr 11. [15824190 ]
  2. Voilley N: Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):71-9. [15032643 ]
  3. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. [15574747 ]
Target Details
6. Potassium voltage-gated channel subfamily KQT member 2
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.
Gene Name:
KCNQ2
Uniprot ID:
O43526
Molecular Weight:
95846.575 Da
References
  1. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [15598972 ]
  2. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. doi: 10.1016/j.tips.2007.11.010. Epub 2008 Jan 18. [18206251 ]
Target Details
7. Potassium voltage-gated channel subfamily KQT member 3
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs.
Gene Name:
KCNQ3
Uniprot ID:
O43525
Molecular Weight:
96741.515 Da
References
  1. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. doi: 10.1016/j.tips.2007.11.010. Epub 2008 Jan 18. [18206251 ]
  2. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [15598972 ]
Target Details
8. Acid-sensing ion channel 1
General Function:
Ligand-gated sodium channel activity
Specific Function:
Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.Isoform 1 does not display proton-gated cation channel activity.
Gene Name:
ASIC1
Uniprot ID:
P78348
Molecular Weight:
59908.915 Da
References
  1. Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33. [11588175 ]