DIMETHADIONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H7NO3
Molecular Weight	129.114
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)OC(=O)NC1=O

InChI

InChIKey=JYJFNDQBESEHJQ-UHFFFAOYSA-N

InChI=1S/C5H7NO3/c1-5(2)3(7)6-4(8)9-5/h1-2H3,(H,6,7,8)

HIDE SMILES / InChI

Molecular Formula	C5H7NO3
Molecular Weight	129.114
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b9322f58-ffcc-4831-5381-93a535b49a09 | https://www.ncbi.nlm.nih.gov/pubmed/12027905 | https://www.ncbi.nlm.nih.gov/pubmed/8925801 | https://www.ncbi.nlm.nih.gov/pubmed/2545161 | https://www.ncbi.nlm.nih.gov/pubmed/26465006 | https://www.ncbi.nlm.nih.gov/pubmed/26311034 | https://www.ncbi.nlm.nih.gov/pubmed/26375719 | https://www.ncbi.nlm.nih.gov/pubmed/6604142

Dimethadione (5,5-dimethyl-2,4-oxazolidinedione) is the N-demethylated metabolite of the anticonvulsant trimethadione. Dimethadione is considered to be a blocker of T-type calcium channel. Dimethadione also inhibits a specific potassium channel (Ikr) in HERG-transfected cells. It exerts teratogenic effect especially congenital heart defects. Dimethadione can be used for the measurement of regional tissue pH using positron emission tomography.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated T-type calcium channel 17 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8925801 \| https://www.ncbi.nlm.nih.gov/pubmed/2545161 \| https://www.ncbi.nlm.nih.gov/pubmed/26465006	Blocker 537
HERG 92 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12027905	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dravet syndrome 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26465006	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Trimethadione N-demethylation by rat liver CYP2E1 in vitro.	1996 Jul	8865369
Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia intestinalis.	2001 Aug 3	11297564
The clinical importance of the trimethadione tolerance test as a method for quantitative assessment of hepatic functional reserve in patients with biliary atresia.	2001 Dec	11722678
Altering intracellular pH disrupts development and cellular organization in preimplantation hamster embryos.	2001 Jun	11369617
Selection of test chemicals for the ECVAM international validation study on in vitro embryotoxicity tests. European Centre for the Validation of Alternative Methods.	2002 Mar-Apr	11971754
Embryonic arrhythmia by inhibition of HERG channels: a common hypoxia-related teratogenic mechanism for antiepileptic drugs?	2002 May	12027905
Disruption of bovine oocytes and preimplantation embryos by urea and acidic pH.	2003 Apr	12741544
Discriminative power of an assay for automated in vitro screening of teratogens.	2004 Aug	15130609
Thoracic skeletal defects and cardiac malformations: a common epigenetic link?	2006 Dec	17315248
Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice.	2006 Jan	16369952
Pharmacological evidence that stalk cell differentiation involves increases in the intracellular Ca(2+) and H(+) concentrations in Dictyostelium discoideum.	2007 Apr	17394603
Polytherapy with hERG-blocking antiepileptic drugs: increased risk for embryonic cardiac arrhythmia and teratogenicity.	2007 Aug	17584909
Embryonic cardiac arrhythmia and generation of reactive oxygen species: common teratogenic mechanism for IKr blocking drugs.	2007 Jul	17570632
Glucose loading precipitates focal lactic acidosis in the vulnerable medial thalamus of thiamine-deficient rats.	2008 Mar	18034292
Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures.	2009	19777068
Acidic and basic solutions dissolve protein plugs made of lithostathine complicating choledochal cyst/pancreaticobiliary maljunction.	2009 Jul	18989781
Alterations in mouse embryo intracellular pH by DMO during culture impair implantation and fetal growth.	2010 Aug	20615756
In utero dimethadione exposure causes postnatal disruption in cardiac structure and function in the rat.	2014 Dec	25239635
Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung.	2014 Dec 4	25446330
In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.	2015 Nov	26311034

Sample Use Guides

In Vivo Use Guide

To generate rats with resolved congenital heart defects, pregnant rats were administered distilled water or dimethadione [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin-stimulated pancreatic secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose of 50, 100 and 200 mg/kg.

Route of Administration: Other

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:13:51 GMT 2023` Edited by `admin` on `Fri Dec 15 15:13:51 GMT 2023`
Record UNII	ALU9NPM703
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DIMETHADIONE

Official Name

English

AC-1198

Code

English

NSC-30152

Code

English

NORTRIMETHADIONE

Common Name

English

DIMETHADIONE [USAN]

Common Name

English

BAY-1400Z

Code

English

5,5-Dimethyl-2,4-oxazolidinedione

Systematic Name

English

DMO

Code

English

2,4-OXAZOLIDINEDIONE, 5,5-DIMETHYL-

Systematic Name

English

dimethadione [INN]

Common Name

English

BAX-1400Z

Code

English

BAX 1400Z

Code

English

EUPRACTONE

Common Name

English

AC 1198

Code

English

DIMETHADIONE [MI]

Common Name

English

Code System Code Type Description

CAS

695-53-4

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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SMS_ID

100000082641

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

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EVMPD

SUB07170MIG

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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EPA CompTox

DTXSID2020478

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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ChEMBL

CHEMBL1099

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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NCI_THESAURUS

C171703

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

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PUBCHEM

3081

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

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ECHA (EC/EINECS)

211-781-4

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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MESH

D004114

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

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INN

1130

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

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MERCK INDEX

m4505

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

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Merck Index

FDA UNII

ALU9NPM703

Created by admin on Fri Dec 15 15:13:51 GMT 2023 , Edited by admin on Fri Dec 15 15:13:51 GMT 2023

PRIMARY

NSC

30152

Created by admin on Fri Dec 15 15:13:52 GMT 2023 , Edited by admin on Fri Dec 15 15:13:52 GMT 2023

PRIMARY

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BINDER->LIGAND

Amount:

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TRIMETHADIONE

PARENT -> METABOLITE ACTIVE

Comments:

Dimethadione has anticonvulsant activity and has been used clinically in the treatment of petit mal epilepsy.


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CHLOROFORM

PARENT -> METABOLITE TOXIC

Comments:

Renal tubular and hepatic necrosis in man.

Related Record Type Details


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DIMETHADIONE

ACTIVE MOIETY

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

PubMed

Sample Use Guides