METAMIZOLE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H17N3O4S
Molecular Weight	311.357
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN(CS(O)(=O)=O)C1=C(C)N(C)N(C1=O)C2=CC=CC=C2

InChI

InChIKey=LVWZTYCIRDMTEY-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C13H17N3O4S
Molecular Weight	311.357
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

Dipyrone, also known as Metamizole (INN), is an ampyrone sulfonate analgesic, antispasmodic and antipyretic. It was withdrawn from US market in 1977 on the basis of reports of agranulocytosis. Depyrone is still used to treat severe and diffucult for relieving pains of different origin; headache, tooth-ache, pains in the joints, muscles, following traumas and operations, gall and kidney colics, neurites, neuralgias, traumatic cerebrasthenia; inflammation of upper respiratory ways of microbial or virus origin; chorea; febrile states. Mechanism of action of dipyrone is complex. It is believed that dipyrone exerts its action by inhibiting COX-3, and activates opioid and cannabioid systems either itself, or by products of its metabolic degradation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostaglandin G/H synthase 1 30	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614	Primary		Approved 8,429	NEURALGIN
Hyperthermia 5	Primary		Approved 8,429	OPTALGIN

C_max

Value	Dose	Analyte	Population
13.85 μg/mL	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens
12.3 μg/mL	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens
13.9 μg/mL	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
69.05 mg × h/L	1 g single, oral		NORAMIDOPYRINE plasma	Homo sapiens
51.33 mg × h/L	1 g single, intravenous		NORAMIDOPYRINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
2.62 h	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens
2.81 h	1 g single, intravenous	NORAMIDOPYRINE plasma	Homo sapiens
2.6 h	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens
4.5 h	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
42.4%	1 g single, oral	NORAMIDOPYRINE plasma	Homo sapiens
52.1%	1 g single, oral	AMPYRONE plasma	Homo sapiens
82.2%	1 g single, oral	4-FORMYLAMINOANTIPYRINE plasma	Homo sapiens
85.8%	1 g single, oral	4-ACETAMINOANTIPYRINE plasma	Homo sapiens

Doses

Doses

Show entries

Dose	Population	Adverse events
1 g 3 times / day multiple, oral Highest studied dose	healthy, ADULT
5 g single, intravenous Studied dose	unhealthy, ADULT

Showing 1 to 2 of 2 entries

Previous1Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587 substrate 1,737	inhibitor 1,767 substrate 1,037 inducer 389	inhibitor 1,852 substrate 1,217 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 882 OATP1B1 788 P-gp 1,461 CYP19A1 60 CYP2C19 1,478 CYP2A6 707 OATP1B3 706 CYP1A2 1,524	CYP2C8 693 CYP1A2 1,054 CYP2C19 991 CYP2B6 664 CYP2E1 667 P-gp 1,537	CYP2B6 547 CYP2C19 293 P-gp 257

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	no [IC50 >10 uM]
CYP2A6 739	inhibitor 3,277	no [IC50 >10 uM]
CYP2C19 1,553	inhibitor 3,277	no [IC50 >10 uM]
CYP2C9 1,819	inhibitor 3,277	no [IC50 >10 uM]
CYP2D6 1,891	inhibitor 3,277	no [IC50 >10 uM]

Showing 1 to 5 of 16 entries

Previous1 2 3 4Next

Drug as victim

Show entries

Target	Modality	Activity	Metabolite
CYP2B6 664	substrate 3,367	major	N-methyl-4-aminoantipyrine
CYP2C8 693	substrate 3,367	major	N-methyl-4-aminoantipyrine
CYP2C9 1,037	substrate 3,367	major	N-methyl-4-aminoantipyrine
CYP3A4 1,737	substrate 3,367	major	N-methyl-4-aminoantipyrine
CYP2E1 667	substrate 3,367	minor	N-methyl-4-aminoantipyrine

Showing 1 to 5 of 9 entries

Previous1 2Next

PubMed

Show entries

Title	Date	PubMed
Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action.	1998 Mar 26	9592021
Metamizol potentiates morphine antinociception but not constipation after chronic treatment.	2002 Apr 26	12063090
Allergic cholestatic hepatitis and exanthema induced by metamizole: verification by lymphocyte transformation test.	2002 Dec	12445177
A comparative study of the antipyretic effects of indomethacin and dipyrone in rats.	2002 Jan	11852909
COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression.	2002 Oct 15	12242329

Showing 1 to 5 of 5 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

Dipyrone was administered orally, as subcutaneous and intramuscular injections (daily dose 0.25-1 g as 50% solution), or by intravenous injection.

Route of Administration: Other

In Vitro Use Guide

Cyclooxygenase activity was measured by the formation of PGE2 after exposure to exogenous 30 μM acid for 10 min. Dipyrone inhibited COX-1 with IC50 350 uM, and COX-3 with IC50 of 52 uM.

Substance Class	Chemical
Record UNII	934T64RMNJ
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

METAMIZOLE

Common Name

English

Metamizole [WHO-DD]

Common Name

English

METHAMIZOLE-

Common Name

English

METHANESULFONIC ACID, (ANTIPYRINYLMETHYLAMINO)-

Common Name

English

METHANESULFONIC ACID, ((2,3-DIHYDRO-1,5-DIMETHYL-3-OXO-2-PHENYL-1H-PYRAZOL-4-YL)METHYLAMINO)-

Common Name

English

Showing 1 to 5 of 7 entries

Previous1 2Next

Show entries

Classification Tree

Code System

Code

Pyrazolones

WHO-ATC

N02BB72

Pyrazolones

WHO-ATC

N02BB52

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Code System

Code

Type

Description

EVMPD

SUB03187MIG

PRIMARY

DAILYMED

934T64RMNJ

PRIMARY

EPA CompTox

DTXSID6044143

PRIMARY

DRUG CENTRAL

4659

PRIMARY

DRUG BANK

DB04817

PRIMARY

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					T2GJX42UMD

METAMIZOLE CALCIUM

SALT/SOLVATE -> PARENT

Amount:


					MS15642725

METAMIZOLE MAGNESIUM

SALT/SOLVATE -> PARENT

Amount:


					D247KUF39V

METAMIZOLE MAGNESIUM HEXAHYDRATE

SALT/SOLVATE -> PARENT

Amount:


					VSU62Z74ON

METAMIZOLE SODIUM

SALT/SOLVATE -> PARENT

Amount:


					6429L0L52Y

DIPYRONE

SALT/SOLVATE -> PARENT

Amount:

Showing 1 to 5 of 5 entries

Previous1Next

Show entries

Related Record

Type

Details


					NER31DE951

NORAMIDOPYRINE

METABOLITE ACTIVE -> PRODRUG

Comments:

Metamizole is rapidly hydrolyzed to 4-MMA in gastric juice and this is the predominat species absorbed.

Interaction Type:

MAJOR

Qualification:

PLASMA; URINE

Amount:


					0M0B7474RA

AMPYRONE

METABOLITE ACTIVE -> PARENT

Showing 1 to 2 of 2 entries

Previous1Next

SMILES

InChI

Description<div class="info-popup-container"><div><span class="pop-sub-key ">Sources:&nbsp;</span><span class="pop-sub-val"><span class="ext-link"><a target="_self" href="http://www.un.org/esa/coordination/CL12.pdf">http://www.un.org/esa/coordination/CL12.pdf</a></span></span></div></div>

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

Description

C_max

T_1/2

F_unbound

Drug as perpetrator