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
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
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
Fluorescence polarization discriminates green fluorescent protein from interfering autofluorescence in a microplate assay for genotoxicity.	2002 Apr 18	12062116
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
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
Aqua-(2,2'-bipyridine-κN,N')bis-(thio-phene-2-carboxyl-ato-κO)copper(II).	2009 Jul 11	21583368
Toxicogenomic biomarkers for liver toxicity.	2009 Mar	22271975
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
Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.	2010 Dec	20801182
Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity.	2011 Dec	21873647
Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.	2012	22363424
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
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
Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury.	2014 Oct 3	24880025

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