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Details

Stereochemistry ACHIRAL
Molecular Formula 2C14H19N3S.3C4H4O4
Molecular Weight 870.988
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 3
Charge 0

SHOW SMILES / InChI
Structure of METHAPYRILENE FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.CN(C)CCN(CC1=CC=CS1)C2=CC=CC=N2.CN(C)CCN(CC3=CC=CS3)C4=CC=CC=N4

InChI

InChIKey=OLGIEIJNOQGBSS-VQYXCCSOSA-N
InChI=1S/2C14H19N3S.3C4H4O4/c2*1-16(2)9-10-17(12-13-6-5-11-18-13)14-7-3-4-8-15-14;3*5-3(6)1-2-4(7)8/h2*3-8,11H,9-10,12H2,1-2H3;3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C14H19N3S
Molecular Weight 261.386
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Methapyrilene is an antihistamine and anticholinergic of the pyridine chemical class which was developed in the early 1950s. It was sold under the trade names Co-Pyronil and Histadyl EC. It has relatively strong sedative effects, to the extent that its primary use was as a medication for insomnia rather than for its antihistamine action. Together with scopolamine, it was the main ingredient in Sominex, Nytol, and Sleep-Eze. It also provided the sedative component of Excedrin PM. Manufacturers voluntarily withdrew methapyrilineb drug products from the market in May and June 1979, when methapyrilene was demonstrated to cause liver cancer in rats when given chronically.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Doses

Doses

DosePopulationAdverse events​
2.5 g single, oral
Overdose
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
healthy, 19 years
Health Status: healthy
Age Group: 19 years
Sex: F
Sources:
Other AEs: Dizziness, Stomach cramps...
Other AEs:
Dizziness
Stomach cramps
Delusions
Sources:
25 mg single, intravenous
Dose: 25 mg
Route: intravenous
Route: single
Dose: 25 mg
Sources:
healthy, 20 - 35 years
Health Status: healthy
Age Group: 20 - 35 years
Sex: M+F
Sources:
50 mg single, oral
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
healthy, 20 - 35 years
Health Status: healthy
Age Group: 20 - 35 years
Sex: M+F
Sources:
AEs

AEs

AESignificanceDosePopulation
Delusions
2.5 g single, oral
Overdose
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
healthy, 19 years
Health Status: healthy
Age Group: 19 years
Sex: F
Sources:
Dizziness
2.5 g single, oral
Overdose
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
healthy, 19 years
Health Status: healthy
Age Group: 19 years
Sex: F
Sources:
Stomach cramps
2.5 g single, oral
Overdose
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
healthy, 19 years
Health Status: healthy
Age Group: 19 years
Sex: F
Sources:
PubMed

PubMed

TitleDatePubMed
Toxicology of vancomycin in laboratory animals.
1981 Nov-Dec
Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene.
1998 Nov
Principal component analysis of mass spectra of peptides generated from the tryptic digestion of protein mixtures.
2001
Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles.
2001 Aug 15
Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.
2001 Mar 31
Tissue distribution of quetiapine in 20 cases in Virginia.
2006 May
Selection of new chemical entities with decreased potential for adverse drug reactions.
2006 Nov 7
Toxicophores: investigations in drug safety.
2006 Sep 1
Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.
2007 Apr
Literature-based compound profiling: application to toxicogenomics.
2007 Nov
Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore.
2008 Aug
Gene expression profiling in rat liver treated with compounds inducing elevation of bilirubin.
2009 Apr
Aqua-(2,2'-bipyridine-κN,N')bis-(thio-phene-2-carboxyl-ato-κO)copper(II).
2009 Jul 11
Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.
2010 Sep 30
Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity.
2011 Dec
The genotoxic potential of methapyrilene using the alkaline Comet assay in vitro and in vivo.
2011 Dec 18
Development and evaluation of a genomic signature for the prediction and mechanistic assessment of nongenotoxic hepatocarcinogens in the rat.
2011 Nov
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.
2014
Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats.
2015 Dec
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Unknown
Route of Administration: Unknown
In Vitro Use Guide
Methapyrilene failed to induce formation of DNA adducts in L5178Y cell DNA at doses which induced mutations at the thymidine kinase locus. These data suggest that methapyrilene induces mutations in this system through an indirect genotoxic mechanism; e.g., via an oxidative mechanism or interaction with chromosomal proteins.
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:33:22 UTC 2023
Edited
by admin
on Wed Jul 05 22:33:22 UTC 2023
Record UNII
KJ5I25TXYL
Record Status Validated (UNII)
Record Version
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Name Type Language
METHAPYRILENE FUMARATE
MI   USP-RS   WHO-DD  
Common Name English
METHAPYRILENE FUMARATE [MI]
Common Name English
1,2-ETHANEDIAMINE, N,N-DIMETHYL-N'-2-PYRIDINYL-N'-(2-THIENYLMETHYL)-, (E)-2-BUTENEDIOATE (2:3)
Common Name English
Methapyrilene fumarate [WHO-DD]
Common Name English
THENYLPYRAMINE FUMARATE
Systematic Name English
2-[[2-(Dimethylamino)ethyl]-2-thenylamino]pyridine fumarate (2:3)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
Code System Code Type Description
CAS
33032-12-1
Created by admin on Wed Jul 05 22:33:22 UTC 2023 , Edited by admin on Wed Jul 05 22:33:22 UTC 2023
PRIMARY
EVMPD
SUB14535MIG
Created by admin on Wed Jul 05 22:33:22 UTC 2023 , Edited by admin on Wed Jul 05 22:33:22 UTC 2023
PRIMARY
NCI_THESAURUS
C83953
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
FDA UNII
KJ5I25TXYL
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
MERCK INDEX
M7301
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY Merck Index
SMS_ID
100000076549
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
ECHA (EC/EINECS)
251-351-3
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
ChEMBL
CHEMBL1411979
Created by admin on Wed Jul 05 22:33:22 UTC 2023 , Edited by admin on Wed Jul 05 22:33:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID0047404
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
PUBCHEM
6436730
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
DRUG BANK
DBSALT002793
Created by admin on Wed Jul 05 22:33:23 UTC 2023 , Edited by admin on Wed Jul 05 22:33:23 UTC 2023
PRIMARY
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