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

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

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
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
Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.	2004 Mar	15033593
Selection of new chemical entities with decreased potential for adverse drug reactions.	2006 Nov 7	16979156
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
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
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
Gene expression profiling of methapyrilene-induced hepatotoxicity in rat.	2008 Feb	18303183
Gene expression profiling in rat liver treated with compounds inducing elevation of bilirubin.	2009 Apr	19734275
Discrimination of carcinogens by hepatic transcript profiling in rats following 28-day administration.	2009 Nov 13	20011461
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
GEM-TREND: a web tool for gene expression data mining toward relevant network discovery.	2009 Sep 3	19728865
Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.	2010 Sep 30	20656055
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.	2014	25058030
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
Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury.	2014 Oct 3	24880025
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 16:14:41 GMT 2023` Edited by `admin` on `Fri Dec 15 16:14:41 GMT 2023`
Record UNII	A01LX40298
Record Status	`Validated (UNII)`
Record Version

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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