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

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
Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene.	1998 Nov	9928682
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
Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats.	2002 Jul	12144742
Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations.	2002 Jul-Aug	12187938
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
Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action.	2005 Sep 29	16005536
Tissue distribution of quetiapine in 20 cases in Virginia.	2006 May	16803670
Selection of new chemical entities with decreased potential for adverse drug reactions.	2006 Nov 7	16979156
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
'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.	2008 Jun 3	18522721
Aqua-(2,2'-bipyridine-κN,N')bis-(thio-phene-2-carboxyl-ato-κO)copper(II).	2009 Jul 11	21583368
GEM-TREND: a web tool for gene expression data mining toward relevant network discovery.	2009 Sep 3	19728865
Characterization of glutathione conjugates of duloxetine by mass spectrometry and evaluation of in silico approaches to rationalize the site of conjugation for thiophene containing drugs.	2010 Aug 16	20669986
Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens.	2012 Aug	22584684
Detection of initiating potential of non-genotoxic carcinogens in a two-stage hepatocarcinogenesis study in rats.	2014	25242409
Changes in the expression of miRNAs at the pericentral and periportal regions of the rat liver in response to hepatocellular injury: comparison with the changes in the expression of plasma miRNAs.	2014 Aug 1	24863736
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.

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