AMINOPHENAZONE

US Previously Marketed

First marketed in 1897

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H17N3O
Molecular Weight	231.2936
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=RMMXTBMQSGEXHJ-UHFFFAOYSA-N

InChI=1S/C13H17N3O/c1-10-12(14(2)3)13(17)16(15(10)4)11-8-6-5-7-9-11/h5-9H,1-4H3

HIDE SMILES / InChI

Description
Sources: http://noillen.bitballoon.com/medicine2/amidopyrine-instruct261 | Vaz, R.J. & Klabunde, T. (2008) Antitargets: Prediction and Prevention of Drug Side Effects, page 5, retrieved from: https://books.google.ru/books?id=oSnSk1kv0dAC | (2004) Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Pharmaceuticals, page 18, retrieved from: https://books.google.ru/books?id=leVCukUgNlsC | Suchy, F.J. et al. (2007) Liver Disease in Children, page 107, retrieved from: https://books.google.ru/books?id=rGxPASmZWesC

Aminophenazone is a phenyl-pyrazolone derivative with potent analgesic and antipyretic properties. Aminophenazone has been used as salt or complexes, including topically as the salicylate. It was recommended for the treatment of a fever, neuralgia, myositis, acute rheumatism, arthritis, chorea. In 1999 the FDA suspended aminophenazone. The drug caused agranulocytosis. Some of the cases of agranulocytosis were fatal. Another reason for suspending this drug from the market was its ability to react with nitrite-containing food, thus forming carcinogenic nitrosamines. A breath test with 13C-labeled aminopyrine has been used as a non-invasive measure of cytochrome P-450 metabolic activity in liver function tests.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase 89 Target ID: CHEMBL2095157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2498559	Inhibitor 8297		3.8 mM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Myositis 7 Sources: http://noillen.bitballoon.com/nutritional-suppleme5/	Palliative	Withdrawn	Pyramidon Approved Use Aminophenazone recommended taking in case of fever, neuralgia, myositis, acute rheumatism, arthritis, chorea.
Arthritis 89 Sources: http://noillen.bitballoon.com/medicine2/amidopyrine-instruct261	Palliative	Withdrawn	Pyramidon Approved Use Aminophenazone recommended taking in case of fever, neuralgia, myositis, acute rheumatism, arthritis, chorea.
Rheumatism 10 Sources: http://noillen.bitballoon.com/medicine2/amidopyrine-instruct261	Palliative	Withdrawn	Pyramidon Approved Use Aminophenazone recommended taking in case of fever, neuralgia, myositis, acute rheumatism, arthritis, chorea.
Neuralgia 12 Sources: http://noillen.bitballoon.com/medicine2/amidopyrine-instruct261	Palliative	Withdrawn	Pyramidon Approved Use Aminophenazone recommended taking in case of fever, neuralgia, myositis, acute rheumatism, arthritis, chorea.

C_max

Value	Dose	Co-administered	Analyte	Population
2.7 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/7002187/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		AMINOPHENAZONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
17.4 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/7002187/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		AMINOPHENAZONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.3 h REVIEW https://pubmed.ncbi.nlm.nih.gov/7002187/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		AMINOPHENAZONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
2.6 h REVIEW https://pubmed.ncbi.nlm.nih.gov/7002187/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		AMINOPHENAZONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
85% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15437290/			AMINOPHENAZONE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
220 mg 1 times / day multiple, oral Recommended Dose: 220 mg, 1 times / day Route: oral Route: multiple Dose: 220 mg, 1 times / day Co-administed with:: allobarbitone(30 mg; 1-2 tablets once or twice per day for 18 days) Sources: https://pubmed.ncbi.nlm.nih.gov/6105412/	unhealthy, 27 years n = 1 Health Status: unhealthy Condition: pain Age Group: 27 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6105412/	Other AEs: Agranulocytosis... Other AEs: Agranulocytosis Sources: https://pubmed.ncbi.nlm.nih.gov/6105412/
10 % 1 times / day single, topical Studied dose Dose: 10 %, 1 times / day Route: topical Route: single Dose: 10 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6627934/	healthy, 28 years n = 1 Health Status: healthy Age Group: 28 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6627934/	Other AEs: Contact urticaria... Other AEs: Contact urticaria Sources: https://pubmed.ncbi.nlm.nih.gov/6627934/
286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	Other AEs: Tiredness, Nausea... Other AEs: Tiredness (13.1%) Nausea (10.7%) Headache (1.2%) Vomiting (1.2%) Mental confusion (5.9%) Palpitation (1.2%) Faintness (1.2%) Loss of memory (1.2%) Urticaria (1.2%) Vertigo (1.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
220 mg 2 times / day multiple, rectal Recommended Dose: 220 mg, 2 times / day Route: rectal Route: multiple Dose: 220 mg, 2 times / day Co-administed with:: codeine(5 mg; 2 per day) diallymal(30 mg; 2 per day) Sources: https://pubmed.ncbi.nlm.nih.gov/4589282/	unhealthy, mean age 6.4 years n = 43 Health Status: unhealthy Condition: pain Age Group: mean age 6.4 years Sex: M+F Population Size: 43 Sources: https://pubmed.ncbi.nlm.nih.gov/4589282/	Other AEs: Vomiting... Other AEs: Vomiting (5.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/4589282/

AEs

AE	Significance	Dose	Population
Agranulocytosis		220 mg 1 times / day multiple, oral Recommended Dose: 220 mg, 1 times / day Route: oral Route: multiple Dose: 220 mg, 1 times / day Co-administed with:: allobarbitone(30 mg; 1-2 tablets once or twice per day for 18 days) Sources: https://pubmed.ncbi.nlm.nih.gov/6105412/	unhealthy, 27 years n = 1 Health Status: unhealthy Condition: pain Age Group: 27 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6105412/
Contact urticaria		10 % 1 times / day single, topical Studied dose Dose: 10 %, 1 times / day Route: topical Route: single Dose: 10 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6627934/	healthy, 28 years n = 1 Health Status: healthy Age Group: 28 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6627934/
Faintness	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Headache	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Loss of memory	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Palpitation	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Urticaria	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Vertigo	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Vomiting	1.2%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Nausea	10.7%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Tiredness	13.1%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Mental confusion	5.9%	286 mg 2 times / day multiple, oral Studied dose Dose: 286 mg, 2 times / day Route: oral Route: multiple Dose: 286 mg, 2 times / day Co-administed with:: barbital(114 mg; 2 per day during 2.5 days) aethylmorphin hydrochlorid(20 mg; 2 per day during 2.5 days) Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/	unhealthy, mean age 24.3 years n = 84 Health Status: unhealthy Condition: pain Age Group: mean age 24.3 years Sex: M+F Population Size: 84 Sources: https://pubmed.ncbi.nlm.nih.gov/3125269/
Vomiting	5.5%	220 mg 2 times / day multiple, rectal Recommended Dose: 220 mg, 2 times / day Route: rectal Route: multiple Dose: 220 mg, 2 times / day Co-administed with:: codeine(5 mg; 2 per day) diallymal(30 mg; 2 per day) Sources: https://pubmed.ncbi.nlm.nih.gov/4589282/	unhealthy, mean age 6.4 years n = 43 Health Status: unhealthy Condition: pain Age Group: mean age 6.4 years Sex: M+F Population Size: 43 Sources: https://pubmed.ncbi.nlm.nih.gov/4589282/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C18 138 CYP2C19 991 CYP2E1 667

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2C18 138	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/12124312/ \| https://pubmed.ncbi.nlm.nih.gov/28057172/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/28057172/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/28057172/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10784435/ \| https://pubmed.ncbi.nlm.nih.gov/19515014/ \| https://pubmed.ncbi.nlm.nih.gov/10199594/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:160246	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:160246
ChemicalBook	CB1476086	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1476086
MolPort	MolPort-001-783-069	https://www.molport.com/shop/molecule-link/MolPort-001-783-069
Selleck Chemicals	amidopyrine	http://www.selleckchem.com/products/amidopyrine.html
ZINC	ZINC000000057115	http://zinc15.docking.org/substances/ZINC000000057115
eMolecules	537453	https://www.emolecules.com/cgi-bin/more?vid=537453

PubMed

Title	Date	PubMed
Short-term study of the effect of phenacetin, phenazone and amidopyrine on the rat kidney.	1968 Jan	5640170
Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite.	1975 Aug 15	168160
Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms.	1977 Mar 12	65671
Role of caffeine in combined analgesic drugs from the point of view of experimental pharmacology.	1997 Aug	9296278
Toxic epidermal necrolysis in a patient with severe aplastic anemia treated with cyclosporin A and G-CSF.	2001	11321886
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.	2002	12898905
Studies on new cyclic imides obtained from aminophenazone with analgesic properties. Potent effects of a 3,4-dichloromaleimide derivative.	2002	12109046
Cloning, expression, and functional characterization of human cyclooxygenase-1 splicing variants: evidence for intron 1 retention.	2005 Dec	16141368
Ethnoveterinary medicines used for ruminants in British Columbia, Canada.	2007 Feb 26	17324258
Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury.	2008	19040780
Oxidation of suspected N-nitrosodimethylamine (NDMA) precursors by ferrate (VI): kinetics and effect on the NDMA formation potential of natural waters.	2008 Jan	17692886
Scavenging activity of aminoantipyrines against hydroxyl radical.	2010 Jun	20172632

Patents

Sample Use Guides

In Vivo Use Guide

250-300 mg 3-4 times a day

Route of Administration: Oral

In Vitro Use Guide

Aminophenazone inhibits rat gastric mucosal 6-keto-prostaglandin F1 alpha production with IC50 3.8x10(-3) M.

Name

Type

Language

AMINOPHENAZONE

Official Name

English

AMINOPYRINE

Common Name

English

aminophenazone [INN]

Common Name

English

AMINOPHENAZONE [MART.]

Common Name

English

Aminophenazone [WHO-DD]

Common Name

English

4-DIMETHYLAMINOANTIPYRINE

Common Name

English

AMINOPYRINE [MI]

Common Name

English

AMINOPYRINE [JAN]

Common Name

English

MAMALLET A

Common Name

English

AMIDOPYRINE

Common Name

English

AMIDOPYRAZOLINE

Common Name

English

FEBRON

Brand Name

English

3H-PYRAZOL-3-ONE, 4-(DIMETHYLAMINO)-1,2-DIHYDRO-1,5-DIMETHYL-2-PHENYL-

Systematic Name

English

4-DIMETHYLAMINO-1,5-DIMETHYL-2-PHENYL-1,2-DIHYDRO-3H-PYRAZOL-3-ONE

Systematic Name

English

NSC-4993

Code

English

DEREUMA

Brand Name

English

ITAMIDONE

Brand Name

English

BRUFANEUXOL

Common Name

English

4-DIMETHYLAMINO-2,3-DIMETHYL-1-PHENYL-3-PYRAZOLIN-5-ONE

Systematic Name

English

METAMIZOLE SODIUM MONOHYDRATE IMPURITY D [EP IMPURITY]

Common Name

English

AMIDAZOPHENE

Common Name

English

AMINOPYRINE [HSDB]

Common Name

English

NETSUSARIN

Brand Name

English

Classification Tree Code System Code

WHO-ATC

N02BB03