METHAPYRILENE HYDROCHLORIDE

US Previously Marketed

First approved in 1947

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H19N3S.ClH
Molecular Weight	297.847
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of METHAPYRILENE HYDROCHLORIDE

Structure Search

SMILES

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

InChI

InChIKey=BONORRGKLJBGRV-UHFFFAOYSA-N

InChI=1S/C14H19N3S.ClH/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;1H

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
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
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
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
Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.	2004 Mar	15033593
Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver.	2005 Aug 4	15890375
Selection of new chemical entities with decreased potential for adverse drug reactions.	2006 Nov 7	16979156
Toxicophores: investigations in drug safety.	2006 Sep 1	16860917
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
Toxicogenomic biomarkers for liver toxicity.	2009 Mar	22271975
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
The genotoxic potential of methapyrilene using the alkaline Comet assay in vitro and in vivo.	2011 Dec 18	22015589
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
Detection of initiating potential of non-genotoxic carcinogens in a two-stage hepatocarcinogenesis study in rats.	2014	25242409
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

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 HYDROCHLORIDE

Common Name

English

METHAPYRILENE HCL

Common Name

English

NSC-758410

Code

English

METHAPYRILENE HYDROCHLORIDE [MI]

Common Name

English

Methapyrilene hydrochloride [WHO-DD]

Common Name

English

METHAPYRILENE HYDROCHLORIDE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578