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

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	ClH
Molecular Weight	36.461
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
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
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
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
Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms.	2004 Mar	15033595
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
Selection of new chemical entities with decreased potential for adverse drug reactions.	2006 Nov 7	16979156
Gene expression profiling of rat liver treated with serum triglyceride-decreasing compounds.	2007 Oct	17965553
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
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
Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.	2012	22363424
Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies.	2013 Oct	23558518
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
Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats.	2015 Dec	26558467

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 15:17:22 GMT 2023` Edited by `admin` on `Fri Dec 15 15:17:22 GMT 2023`
Record UNII	00S42N58OM
Record Status	`Validated (UNII)`
Record Version

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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