Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | 2C14H19N3S.3C4H4O4 |
| Molecular Weight | 870.988 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 3 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.CN(C)CCN(CC1=CC=CS1)C2=CC=CC=N2.CN(C)CCN(CC3=CC=CS3)C4=CC=CC=N4
InChI
InChIKey=OLGIEIJNOQGBSS-VQYXCCSOSA-N
InChI=1S/2C14H19N3S.3C4H4O4/c2*1-16(2)9-10-17(12-13-6-5-11-18-13)14-7-3-4-8-15-14;3*5-3(6)1-2-4(7)8/h2*3-8,11H,9-10,12H2,1-2H3;3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+
| 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 | C4H4O4 |
| Molecular Weight | 116.0722 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB04819
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
Doses
| Dose | Population | Adverse events |
|---|---|---|
2.5 g single, oral Overdose |
healthy, 19 years |
Other AEs: Dizziness, Stomach cramps... |
25 mg single, intravenous Dose: 25 mg Route: intravenous Route: single Dose: 25 mg Sources: |
healthy, 20 - 35 years Health Status: healthy Age Group: 20 - 35 years Sex: M+F Sources: |
|
50 mg single, oral |
healthy, 20 - 35 years Health Status: healthy Age Group: 20 - 35 years Sex: M+F Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Delusions | 2.5 g single, oral Overdose |
healthy, 19 years |
|
| Dizziness | 2.5 g single, oral Overdose |
healthy, 19 years |
|
| Stomach cramps | 2.5 g single, oral Overdose |
healthy, 19 years |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Toxicology of vancomycin in laboratory animals. | 1981 Nov-Dec |
|
| The carcinogenic effect of methapyrilene combined with nitrosodiethylamine given to rats in low doses. | 1992 Jul |
|
| Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene. | 1998 Nov |
|
| Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling. | 2004 Apr |
|
| Discriminating different classes of toxicants by transcript profiling. | 2004 Aug |
|
| Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms. | 2004 Mar |
|
| Cross-site comparison of gene expression data reveals high similarity. | 2004 Mar |
|
| Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene. | 2004 Mar |
|
| Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. | 2004 Mar |
|
| Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. | 2004 May 18 |
|
| Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. | 2005 Aug 4 |
|
| Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. | 2005 Sep 29 |
|
| Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study. | 2006 Jan |
|
| Recent applications of DNA microarray technology to toxicology and ecotoxicology. | 2006 Jan |
|
| Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. | 2006 Jul |
|
| Tissue distribution of quetiapine in 20 cases in Virginia. | 2006 May |
|
| Selection of new chemical entities with decreased potential for adverse drug reactions. | 2006 Nov 7 |
|
| Toxicophores: investigations in drug safety. | 2006 Sep 1 |
|
| Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. | 2007 Apr |
|
| Literature-based compound profiling: application to toxicogenomics. | 2007 Nov |
|
| Gene expression profiling of rat liver treated with serum triglyceride-decreasing compounds. | 2007 Oct |
|
| Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore. | 2008 Aug |
|
| A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. | 2008 Aug 19 |
|
| Primary rat hepatocytes as in vitro system for gene expression studies: comparison of sandwich, Matrigel and 2D cultures. | 2008 Dec |
|
| Gene expression profiling of methapyrilene-induced hepatotoxicity in rat. | 2008 Feb |
|
| 'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus. | 2008 Jun 3 |
|
| Gene expression profiling in rat liver treated with compounds inducing elevation of bilirubin. | 2009 Apr |
|
| Aqua-(2,2'-bipyridine-κN,N')bis-(thio-phene-2-carboxyl-ato-κO)copper(II). | 2009 Jul 11 |
|
| Toxicogenomic biomarkers for liver toxicity. | 2009 Mar |
|
| Discrimination of carcinogens by hepatic transcript profiling in rats following 28-day administration. | 2009 Nov 13 |
|
| Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosis. | 2009 Sep 15 |
|
| GEM-TREND: a web tool for gene expression data mining toward relevant network discovery. | 2009 Sep 3 |
|
| 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 |
|
| Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens. | 2010 Dec |
|
| Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies. | 2010 Sep 30 |
|
| Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. | 2011 Dec |
|
| The genotoxic potential of methapyrilene using the alkaline Comet assay in vitro and in vivo. | 2011 Dec 18 |
|
| Development and evaluation of a genomic signature for the prediction and mechanistic assessment of nongenotoxic hepatocarcinogens in the rat. | 2011 Nov |
|
| Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis. | 2012 |
|
| Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens. | 2012 Aug |
|
| Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver. | 2012 Sep |
|
| Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes. | 2013 Feb |
|
| Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies. | 2013 Oct |
|
| Detection of initiating potential of non-genotoxic carcinogens in a two-stage hepatocarcinogenesis study in rats. | 2014 |
|
| Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. | 2014 |
|
| 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 |
|
| Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats. | 2014 Oct 3 |
|
| Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury. | 2014 Oct 3 |
|
| Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats. | 2015 Dec |
|
| Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure. | 2015 Dec 1 |
Patents
Sample Use Guides
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
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| Record UNII |
KJ5I25TXYL
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| Record Status |
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| Record Version |
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C29578
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