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 |
|---|---|---|
| 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 |
|
| Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. | 2001 Aug 15 |
|
| Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat. | 2002 Dec 2 |
|
| Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. | 2002 Jul |
|
| Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. | 2002 Jul-Aug |
|
| Protein expression analysis of drug-mediated hepatotoxicity in the Sprague-Dawley rat. | 2002 Nov |
|
| Diphenhydramine-induced wide complex dysrhythmia responds to treatment with sodium bicarbonate. | 2003 May |
|
| Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling. | 2004 Apr |
|
| Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. | 2004 Mar |
|
| Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study. | 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 |
|
| Toxicophores: investigations in drug safety. | 2006 Sep 1 |
|
| Literature-based compound profiling: application to toxicogenomics. | 2007 Nov |
|
| Gene expression profiling of methapyrilene-induced hepatotoxicity in rat. | 2008 Feb |
|
| 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 |
|
| Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. | 2011 Dec |
|
| 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 |
|
| Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. | 2014 |
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
by
admin
on
Edited
Fri Dec 16 15:56:29 UTC 2022
by
admin
on
Fri Dec 16 15:56:29 UTC 2022
|
| Record UNII |
KJ5I25TXYL
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
NCI_THESAURUS |
C29578
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
33032-12-1
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
SUB14535MIG
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
C83953
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
KJ5I25TXYL
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
M7301
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | Merck Index | ||
|
251-351-3
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
CHEMBL1411979
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
DTXSID0047404
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
6436730
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY | |||
|
DBSALT002793
Created by
admin on Fri Dec 16 15:56:29 UTC 2022 , Edited by admin on Fri Dec 16 15:56:29 UTC 2022
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
PARENT -> SALT/SOLVATE | |||
|
|
PARENT -> SALT/SOLVATE |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |