METHAPYRILENE FUMARATE

US Previously Marketed

First approved in 1947

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 Search

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	C14H19N3S
Molecular Weight	261.386
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

Description
Sources: http://www.drugbank.ca/drugs/DB04819

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

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

Doses

Dose	Population	Adverse events
2.5 g single, oral Overdose Dose: 2.5 g Route: oral Route: single Dose: 2.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/913071	healthy, 19 years Health Status: healthy Age Group: 19 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/913071	Other AEs: Dizziness, Stomach cramps... Other AEs: Dizziness Stomach cramps Delusions Sources: https://pubmed.ncbi.nlm.nih.gov/913071
25 mg single, intravenous Dose: 25 mg Route: intravenous Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7471621	healthy, 20 - 35 years Health Status: healthy Age Group: 20 - 35 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7471621	Sources: https://pubmed.ncbi.nlm.nih.gov/7471621
50 mg single, oral Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7471621	healthy, 20 - 35 years Health Status: healthy Age Group: 20 - 35 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7471621	Sources: https://pubmed.ncbi.nlm.nih.gov/7471621

AEs

AE	Dose	Population
Delusions	2.5 g single, oral Overdose Dose: 2.5 g Route: oral Route: single Dose: 2.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/913071	healthy, 19 years Health Status: healthy Age Group: 19 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/913071
Dizziness	2.5 g single, oral Overdose Dose: 2.5 g Route: oral Route: single Dose: 2.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/913071	healthy, 19 years Health Status: healthy Age Group: 19 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/913071
Stomach cramps	2.5 g single, oral Overdose Dose: 2.5 g Route: oral Route: single Dose: 2.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/913071	healthy, 19 years Health Status: healthy Age Group: 19 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/913071

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1O5MA9
Chemieliva Pharmaceutical Co., Ltd	PBCM1275999
NovoSeek	6436730
PubChem	6436730	https://pubchem.ncbi.nlm.nih.gov/compound/6436730

PubMed

Title	Date	PubMed
Toxicology of vancomycin in laboratory animals.	1981 Nov-Dec	7342285
The carcinogenic effect of methapyrilene combined with nitrosodiethylamine given to rats in low doses.	1992 Jul	1638702
Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene.	1998 Nov	9928682
Principal component analysis of mass spectra of peptides generated from the tryptic digestion of protein mixtures.	2001	11291120
Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles.	2001 Aug 15	11509024
Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.	2001 Mar 31	11323195
Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats.	2001 Sep	11522753
Morphological transformation of Syrian hamster embryo cells at pH 6.7 by bemitradine, a nongenotoxic carcinogen.	2001 Summer	11690565
Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat.	2002 Dec 2	12393293
Cross-site comparison of gene expression data reveals high similarity.	2004 Mar	15033594
Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.	2004 Mar	15033593
Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression.	2004 Mar	15033591
Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver.	2005 Aug 4	15890375
Tissue distribution of quetiapine in 20 cases in Virginia.	2006 May	16803670
Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.	2007 Apr	17450226
Literature-based compound profiling: application to toxicogenomics.	2007 Nov	18034617
Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore.	2008 Aug	18451316
A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats.	2008 Aug 19	18619722
Primary rat hepatocytes as in vitro system for gene expression studies: comparison of sandwich, Matrigel and 2D cultures.	2008 Dec	18987846
Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.	2010 Dec	20801182
Development and evaluation of a genomic signature for the prediction and mechanistic assessment of nongenotoxic hepatocarcinogens in the rat.	2011 Nov	21813463
Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens.	2012 Aug	22584684
Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver.	2012 Sep	22484513
Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes.	2013 Feb	23274394
Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats.	2015 Dec	26558467
Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure.	2015 Dec 1	26431795

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 `Fri Dec 15 15:01:18 GMT 2023` Edited by `admin` on `Fri Dec 15 15:01:18 GMT 2023`
Record UNII	KJ5I25TXYL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHAPYRILENE FUMARATE

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