Identification

Name
Metamizole
Accession Number
DB04817
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Metamizole, formerly marketed as Dimethone tablets and injection, Protemp oral liquid, and other drug products, was associated with potentially fatal agranulocytosis. Approvals of the NDA's for dipyrone drug products were withdrawn on June 27, 1977 (see the Federal Register of June 17, 1977 (42 FR 30893)). Withdrawn from the Canadian market in 1963.

Structure
Thumb
Synonyms
  • metamizol
Product Ingredients
IngredientUNIICASInChI Key
Metamizole magnesiumMS156427256150-97-6NHMUJYOBLYTIKO-UHFFFAOYSA-L
Metamizole sodiumVSU62Z74ON68-89-3DJGAAPFSPWAYTJ-UHFFFAOYSA-M
Metamizole sodium monohydrate6429L0L52Y5907-38-0UNZIDPIPYUMVPA-UHFFFAOYSA-M
International/Other Brands
Algocalmin / Algozone / Analgin / Dimethone / Dipirona / Neo-Melubrina / Novalgin / Optalgin / Protemp / Pyralgin
Categories
UNII
934T64RMNJ
CAS number
50567-35-6
Weight
Average: 311.36
Monoisotopic: 311.093977213
Chemical Formula
C13H17N3O4S
InChI Key
LVWZTYCIRDMTEY-UHFFFAOYSA-N
InChI
InChI=1S/C13H17N3O4S/c1-10-12(14(2)9-21(18,19)20)13(17)16(15(10)3)11-7-5-4-6-8-11/h4-8H,9H2,1-3H3,(H,18,19,20)
IUPAC Name
[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(methyl)amino]methanesulfonic acid
SMILES
CN(CS(O)(=O)=O)C1=C(C)N(C)N(C1=O)C1=CC=CC=C1

Pharmacology

Indication

Used in the past as a powerful painkiller and fever reducer.

Pharmacodynamics

Dipyrone is a non-steroidal anti-inflammatory drug (NSAID), commonly used in the past as a powerful painkiller and fever reducer.

Mechanism of action
TargetActionsOrganism
UProstaglandin G/H synthase 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Metamizole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Metamizole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Metamizole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Metamizole.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Metamizole.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Metamizole.
AbacavirMetamizole may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Metamizole is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Metamizole.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Metamizole.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D08188
PubChem Compound
522325
PubChem Substance
46509035
ChemSpider
3000
BindingDB
235671
ChEBI
62088
ChEMBL
CHEMBL461522
Therapeutic Targets Database
DNC000568
PharmGKB
PA166128206
Wikipedia
Metamizole
ATC Codes
N02BB02 — Metamizole sodiumN02BB72 — Metamizole sodium, combinations with psycholepticsN02BB52 — Metamizole sodium, combinations excl. psycholeptics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
2CompletedTreatmentOther Acute Postoperative Pain1
2CompletedTreatmentPostoperative pain1
2RecruitingNot AvailableChildren / General Surgery / Pain NOS1
3CompletedTreatmentMigraine Disorders1
3CompletedTreatmentPostoperative pain1
3SuspendedNot AvailableFevers / Sepsis1
3TerminatedTreatmentGastroenteritis1
4CompletedTreatmentFevers1
4Not Yet RecruitingTreatmentCesarean Section / Pain, Neuropathic / Postoperative pain1
4Not Yet RecruitingTreatmentCesarean Section / Postoperative pain1
4Not Yet RecruitingTreatmentRenal Colic1
4RecruitingPreventionAnaesthesia therapy / Hip Fractures1
4RecruitingTreatmentCesarean Section / Pain Management / Pain, Neuropathic1
4RecruitingTreatmentPost-Cesarean Section / Postoperative pain1
4RecruitingTreatmentPostoperative pain1
4TerminatedTreatmentPain NOS1
4TerminatedTreatmentStrokes1
Not AvailableCompletedBasic SciencePlatelet Aggregation1
Not AvailableCompletedDiagnosticLumbar Disc Disease1
Not AvailableCompletedDiagnosticPost-Operative Nausea and Vomiting (PONV) / Postoperative pain / Postoperative; Parotitis / Vitreoretinal Surgery1
Not AvailableRecruitingPreventionPost-Operative Nausea and Vomiting (PONV) / Postoperative pain / Vitreoretinal Surgery1
Not AvailableUnknown StatusTreatmentPain Relief1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Zhejiang Haisen Pharmaceutical Co. Ltd.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.53 mg/mLALOGPS
logP-0.4ALOGPS
logP-0.82ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)-1.4ChemAxon
pKa (Strongest Basic)-0.54ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area81.16 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity80.04 m3·mol-1ChemAxon
Polarizability31.41 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7868
Blood Brain Barrier+0.8896
Caco-2 permeable-0.5869
P-glycoprotein substrateNon-substrate0.8148
P-glycoprotein inhibitor INon-inhibitor0.828
P-glycoprotein inhibitor IINon-inhibitor0.8107
Renal organic cation transporterNon-inhibitor0.921
CYP450 2C9 substrateNon-substrate0.8588
CYP450 2D6 substrateNon-substrate0.7959
CYP450 3A4 substrateSubstrate0.6035
CYP450 1A2 substrateNon-inhibitor0.7153
CYP450 2C9 inhibitorNon-inhibitor0.7064
CYP450 2D6 inhibitorNon-inhibitor0.8562
CYP450 2C19 inhibitorNon-inhibitor0.6768
CYP450 3A4 inhibitorNon-inhibitor0.9297
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8506
Ames testAMES toxic0.7763
CarcinogenicityCarcinogens 0.8197
BiodegradationReady biodegradable0.7192
Rat acute toxicity2.6224 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8411
hERG inhibition (predictor II)Non-inhibitor0.6724
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Saussele T, Burk O, Blievernicht JK, Klein K, Nussler A, Nussler N, Hengstler JG, Eichelbaum M, Schwab M, Zanger UM: Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther. 2007 Sep;82(3):265-74. doi: 10.1038/sj.clpt.6100138. Epub 2007 Mar 7. [PubMed:17344806]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on September 11, 2007 14:09 / Updated on November 17, 2018 07:28