METHAPYRILENE

US Previously Marketed

First approved in 1947

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H19N3S
Molecular Weight	261.386
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCN(CC1=CC=CS1)C2=CC=CC=N2

InChI

InChIKey=HNJJXZKZRAWDPF-UHFFFAOYSA-N

InChI=1S/C14H19N3S/c1-16(2)9-10-17(12-13-6-5-11-18-13)14-7-3-4-8-15-14/h3-8,11H,9-10,12H2,1-2H3

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
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
The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.	2001	11695550
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
Fluorescence polarization discriminates green fluorescent protein from interfering autofluorescence in a microplate assay for genotoxicity.	2002 Apr 18	12062116
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
Protein expression analysis of drug-mediated hepatotoxicity in the Sprague-Dawley rat.	2002 Nov	12442256
Diphenhydramine-induced wide complex dysrhythmia responds to treatment with sodium bicarbonate.	2003 May	12811715
Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling.	2004 Apr	15089088
Discriminating different classes of toxicants by transcript profiling.	2004 Aug	15345370
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
Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression.	2004 Mar	15033591
Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants.	2004 May 18	15120968
Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver.	2005 Aug 4	15890375
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
Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study.	2006 Jan	16393664
Recent applications of DNA microarray technology to toxicology and ecotoxicology.	2006 Jan	16393650
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
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
Gene expression profiling in rat liver treated with compounds inducing elevation of bilirubin.	2009 Apr	19734275
Toxicogenomic biomarkers for liver toxicity.	2009 Mar	22271975
Discrimination of carcinogens by hepatic transcript profiling in rats following 28-day administration.	2009 Nov 13	20011461
GEM-TREND: a web tool for gene expression data mining toward relevant network discovery.	2009 Sep 3	19728865
Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.	2010 Dec	20801182
Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.	2010 Sep 30	20656055
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
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
Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats.	2014 Oct 3	25051504
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

Official Name

English

METHAPYRILENE [HSDB]

Common Name

English

SLEEPWELL

Brand Name

English

THIONYLAN

Common Name

English

RESTRYL

Brand Name

English

Methapyrilene [WHO-DD]

Common Name

English

A-3322

Common Name

English

METHAPYRILENE [MI]

Common Name

English

TENALIN

Common Name

English

methapyrilene [INN]

Common Name

English

METHAPYRILENE [MART.]

Common Name

English

2-((2-(DIMETHYLAMINO)ETHYL)-2-THENYLAMINO)PYRIDINE

Systematic Name

English

SEMIKON

Brand Name

English

METAPYRILENE

Common Name

English

A 3322

Common Name

English

PYRINISTOL

Common Name

English

METHAPYRILENE [VANDF]

Common Name

English

1,2-ETHANEDIAMINE, N,N-DIMETHYL-N'-2-PYRIDINYL-N'-(2-THIENYLMETHYL)-

Systematic Name

English

THENYLPYRAMINE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578