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
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
Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.	2001 Mar 31	11323195
Fluorescence polarization discriminates green fluorescent protein from interfering autofluorescence in a microplate assay for genotoxicity.	2002 Apr 18	12062116
Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms.	2004 Mar	15033595
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
Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study.	2006 Jan	16393664
Toxicophores: investigations in drug safety.	2006 Sep 1	16860917
Literature-based compound profiling: application to toxicogenomics.	2007 Nov	18034617
Gene expression profiling of rat liver treated with serum triglyceride-decreasing compounds.	2007 Oct	17965553
Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore.	2008 Aug	18451316
Gene expression profiling of methapyrilene-induced hepatotoxicity in rat.	2008 Feb	18303183
Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosis.	2009 Sep 15	19523481
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
The genotoxic potential of methapyrilene using the alkaline Comet assay in vitro and in vivo.	2011 Dec 18	22015589
Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver.	2012 Sep	22484513
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
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 UTC 2023` Edited by `admin` on `Fri Dec 15 15:01:18 UTC 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