TRIMETHADIONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H9NO3
Molecular Weight	143.1406
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)OC(C)(C)C1=O

InChI

InChIKey=IRYJRGCIQBGHIV-UHFFFAOYSA-N

InChI=1S/C6H9NO3/c1-6(2)4(8)7(3)5(9)10-6/h1-3H3

HIDE SMILES / InChI

Molecular Formula	C6H9NO3
Molecular Weight	143.1406
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/005856s021lbl.pdf

Trimethadione (brand name is TRIDIONE) is an oxazolidinedione compound that was developed as an antiepileptic agent for control of petit mal seizures that are refractory to treatment with other drugs. Tridione does not modify the maximal seizure pattern in patients undergoing electroconvulsive therapy and has a sedative effect that may increase to the point of ataxia when excessive doses are used. Trimethadione acts as a voltage-activated T-type Ca2+ channel blocker. Trimethadione is rapidly absorbed from the gastrointestinal tract. It is demethylated by liver microsomes to the active metabolite, dimethadione. Approximately 3% of a daily dose of tridione is recovered in the urine as the unchanged drug. The majority of trimethadione is excreted slowly by the kidney in the form of dimethadione.

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/16171802	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Petit mal seizures 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/005856s021lbl.pdf	Primary		Approved 8429	TRIDIONE Approved Use INDICATIONS TRIDIONE (trimethadione) is indicated for the control of petit mal seizures that are refractory to treatment with other drugs. Launch Date -7.5530882E11

C_max

Value	Dose	Co-administered	Analyte	Population
6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8441739/	4 mg/kg single, oral dose: 4 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHADIONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
148 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8441739/	4 mg/kg single, oral dose: 4 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHADIONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8441739/	4 mg/kg single, oral dose: 4 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHADIONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
150 mg 4 times / day multiple, oral Dose: 150 mg, 4 times / day Route: oral Route: multiple Dose: 150 mg, 4 times / day Co-administed with:: phenobarbital(15 mg. four times daily.) Sources: https://pubmed.ncbi.nlm.nih.gov/13760024	unhealthy, 16 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 16 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13760024	Disc. AE: Hepatitis... AEs leading to discontinuation/dose reduction: Hepatitis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/13760024
0.3 g 3 times / day multiple, oral (starting) Dose: 0.3 g, 3 times / day Route: oral Route: multiple Dose: 0.3 g, 3 times / day Co-administed with:: phénobarbital(4 grains (0.25 Gm.) daily) Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	Disc. AE: Aplastic anemia... AEs leading to discontinuation/dose reduction: Aplastic anemia (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
0.3 g 3 times / day multiple, oral (starting) Dose: 0.3 g, 3 times / day Route: oral Route: multiple Dose: 0.3 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	Disc. AE: Agranulocytosis, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Agranulocytosis (grade 5, 1 patient) Thrombocytopenia (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
24 g 1 times / day multiple, oral Studied dose Dose: 24 g, 1 times / day Route: oral Route: multiple Dose: 24 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18896724	unhealthy n = 1 Health Status: unhealthy Condition: tetanus Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18896724	Sources: https://pubmed.ncbi.nlm.nih.gov/18896724

AEs

AE	Significance	Dose	Population
Hepatitis	1 patient Disc. AE	150 mg 4 times / day multiple, oral Dose: 150 mg, 4 times / day Route: oral Route: multiple Dose: 150 mg, 4 times / day Co-administed with:: phenobarbital(15 mg. four times daily.) Sources: https://pubmed.ncbi.nlm.nih.gov/13760024	unhealthy, 16 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 16 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13760024
Aplastic anemia	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral (starting) Dose: 0.3 g, 3 times / day Route: oral Route: multiple Dose: 0.3 g, 3 times / day Co-administed with:: phénobarbital(4 grains (0.25 Gm.) daily) Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
Agranulocytosis	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral (starting) Dose: 0.3 g, 3 times / day Route: oral Route: multiple Dose: 0.3 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
Thrombocytopenia	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral (starting) Dose: 0.3 g, 3 times / day Route: oral Route: multiple Dose: 0.3 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20995214	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20995214

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
T-type Ca2+ channels 3 Ca2+ channels 57	CYP 270 CYP1A2 1054 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 60	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25256602/	yes
T-type Ca2+ channels 3	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16171802/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	inconclusive
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/005856s021lbl.pdf Page: 7.0	likely
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	yes
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/14651673/; https://pubmed.ncbi.nlm.nih.gov/9879636/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/12027905/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY515757	https://www.001chemical.com/chem/127-48-0
3B Scientific (Wuhan) Corp	3B3-053075	http://www.3bsc.com/index/pro_info.php?id=91540
AA Blocks	AA000WG2	https://www.aablocks.com/goods/Goods/detail?id=AA000WG2
AHH Chemical co.,ltd	MT-37010	http://www.ahhchemical.com/product/MT-37010.html
Aaron Chemicals	AR000X7U	http://www.aaronchem.com/127-48-0
AbMole Bioscience	M6038	http://www.abmole.com/products/trimethadione.html
Achemica	ACMC-1BYOW	http://www.achemica.com/prodinfo/?id=75259
Alichem	490008683	http://www.alichem.com/en/products/127-48-0.html
Ambeed	A220146	https://www.ambeed.com/products/127-48-0.html
Angel Pharmatech	AG192272	http://www.angelpharmatech.com/127-48-0.html
Aurora Fine Chemicals LLC	A17.879.541	http://online.aurorafinechemicals.com/info?ID=A17.879.541
Avantor Inc	101096-360	https://us.vwr.com/store/catalog/product.jsp?catalog_number=101096-360
BLD Pharm	BD82238	http://www.bldpharm.com/products/127-48-0.html
BioSynth	J-005496	https://www.biosynth.com/en/products/all-products/products/J-005496.html
CSNpharm	CSN19336	https://www.csnpharm.com/products/trimethadione.html
Chem Scene	CS-4339	http://www.chemscene.com/127-48-0.html
Chemenu	CM110354	http://www.chemenu.com/products/CM110354
Chemspace	CSSB00000034190	https://chem-space.com/CSSB00000034190
Clearsynth	CS-EB-02170	https://www.clearsynth.com/en/CSEB02170.html
Clearsynth	CS-ER-02166	https://www.clearsynth.com/en/CSER02166.html
DC Chemicals	DC31900	http://www.dcchemicals.com//product_show-Tridione.html
Finetech	FT-0694585	http://www.finetechnology-ind.com/prod/detail/pub/127-48-0.html
LGC Standards	LGCAMP1669.00-01	https://www.lgcstandards.com/US/en/p/LGCAMP1669.00-01
LGC Standards	LGCFOR1669.00	https://www.lgcstandards.com/US/en/p/LGCFOR1669.00
LGC Standards	MM1669.00	https://www.lgcstandards.com/US/en/p/MM1669.00
Lab Network	LN01303924	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01303924
MedChem Express	HY-A0092	https://www.medchemexpress.com/Trimethadione.html
Molcore	MC515757	https://www.molcore.com/product/127-48-0
MuseChem	I001095	https://www.musechem.com/product/I001095.html
Parchem	30215	http://www.parchem.com/chemical-supplier-distributor/Trimethadione-020215.aspx
Sigma-Aldrich	T0781_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/t0781?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	T2100000_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/t2100000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1690000_USP	https://www.sigmaaldrich.com/catalog/product/usp/1690000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S545889	http://www.smolecule.com/products/s545889
THE BioTek	bt-287010	https://www.thebiotek.com/product/inhibitors/bt-287010
Yuhao Chemical	HL1541	http://www.chemyuhao.com/127-48-0.html
abcr GmbH	AB133755	http://www.abcr.com/shop/en/AB133755
eNovation Chemicals	D673674	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673674
iChemical	EBD71235	http://www.ichemical.com/products/127-48-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-4761457520	https://mcule.com/MCULE-4761457520

PubMed

Title	Date	PubMed
Successful therapy of trimethadione nephrosis with prednisone and cyclophosphamide. Report of a case.	1967 Aug	4961747
Nephrotic syndrome caused by probenecid.	1967 Jan 2	6071127
Pharmacologic interactions of albutoin with other anticonvulsant drugs.	1970 Aug	5451364
Possible teratogenicity of trimethadione and paramethadione.	1970 Aug 1	4193708
Myasthenia gravis syndrome associated with trimethadione.	1970 Jun 29	4987393
Trimethadione (Tridione)-induced nephrotic syndrome. A report of a case with unique ultrastructural renal pathology.	1973 Feb	4631174
Fetal anomalies following maternal trimethadione ingestion.	1973 May	4572938
The fetal trimethadione syndrome.	1975 Aug	50427
Di-n-propylacetic acid--profile of anticonvulsant activity in mice.	1976 Feb	779804
Measurement of anticonvulsant activity in the Papio papio model of epilepsy.	1976 Sep	821787
[Quantitative analysis of conditional-optimal doses of succilep and trimetin in the treatment of children and adolescents with minor forms of epilepsy].	1977	409014
Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect.	1978 Feb	565846
Phenotypic malformations in association with maternal trimethadione therapy.	1978 Feb	413897
Troxidone (trimethadione) embryopathy: case report with reveiw of the literature.	1979	550945
Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin.	1980 Nov 28	6254150
Comparison of the actions of trimethadione and chlordiazepoxide in animal models of anxiety and benzodiazepine receptor binding.	1982 Nov	6129593
Fetal anticonvulsant syndrome in rats: dose- and period-response relationships of prenatal diphenylhydantoin, trimethadione and phenobarbital exposure on the structural and functional development of the offspring.	1983 Nov	6195326
A model of chronic spontaneous petit mal-like seizures in the rat: comparison with pentylenetetrazol-induced seizures.	1984 Jun	6426943
Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat.	1985	3922381
Fetal anticonvulsant syndrome in rats: effects on postnatal behavior and brain amino acid content.	1985 Sep-Oct	4080065
Only certain antiepileptic drugs prevent seizures induced by pilocarpine.	1987 Jul	3607518
Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts.	1988 Sep	2905779
Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat.	1988 Sep-Oct	3137016
Effects of the oxazolidinedione anticonvulsants trimethadione and dimethadione and the barbiturate homolog 5,5-dimethylbarbituric acid on N-nitrosodiethylamine-initiated renal and hepatic carcinogenesis in the F344/NCr rat.	1992	1444806
Dissolution of pancreatic stones by oral trimethadione in patients with chronic calcific pancreatitis.	1994 Sep-Oct	7827299
Anticonvulsants for soman-induced seizure activity.	1999 Mar-Apr	10087439
[Fetal trimethadione syndrome].	2001	11462643
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.	2001 Dec	11738929
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
Determination of trimetazidine HCl by adsorptive stripping square-wave voltammetry at a glassy carbon electrode.	2002 Jan 1	11682231
Embryonic arrhythmia by inhibition of HERG channels: a common hypoxia-related teratogenic mechanism for antiepileptic drugs?	2002 May	12027905
Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes.	2003 Dec	14651673
The history of barbiturates a century after their clinical introduction.	2005 Dec	18568113
Adulteration of South African traditional herbal remedies.	2005 Feb	15665751
The ethics of excluding women who become pregnant while participating in clinical trials of anti-epileptic medications.	2006 Dec	17011799
Education and imaging. Hepatobiliary and pancreatic: oral therapy for pancreatic duct stones.	2006 Sep	16911703
Classification and diagnosis of ear malformations.	2007	22073081
Treatment of Lennox-Gastaut syndrome: overview and recent findings.	2008 Dec	19337447
Etiology of congenital dislocation of the hip : Carl E. Badgley MD (1893-1973). The 11th president of the AAOS 1942.	2008 Jan	18196378
Effect of optical flow versus attentional strategy on gait in Parkinson's Disease: a study with a portable optical stimulating device.	2008 Jan 18	18205903
Valproic acid extends Caenorhabditis elegans lifespan.	2008 Jun	18248662
The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan.	2008 Oct	18949032
Neuroprotective effects of blockers for T-type calcium channels.	2009 Oct 28	19863782
Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.	2010 Feb	19430925
Allyl isothiocyanate that induces GST and UGT expression confers oxidative stress resistance on C. elegans, as demonstrated by nematode biosensor.	2010 Feb 17	20174640
Zebrafish (Danio rerio) embryos as a model for testing proteratogens.	2011 Mar 15	21237239

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dosage: 0.9-2.4 grams daily in 3 or 4 equally divided doses (i.e., 300−600 mg 3 or 4 times daily). Initially, give 0.9 gram daily; increase this dose by 300 mg at weekly intervals until therapeutic results are seen or until toxic symptoms appear. Children's Dosage: Usually 0.3-0.9 gram daily in 3 or 4 equally divided doses.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:07:51 UTC 2023` Edited by `admin` on `Fri Dec 15 15:07:51 UTC 2023`
Record UNII	R7GV3H6FQ4
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TRIMETHADIONE

Official Name

English

EPIDIONE

Common Name

English

TRIMETHADIONE [WHO-IP]

Common Name

English

TRIMETHADIONE [EP MONOGRAPH]

Common Name

English

NSC-15799

Code

English

TRIMETHADIONE [MI]

Common Name

English

ABSENTOL

Common Name

English

J2.519D

Code

English

A 2297

Code

English

TRIMETHADIONE [USP-RS]

Common Name

English

TRIMETHADIONE [ORANGE BOOK]

Common Name

English

TRIMETHADIONUM [WHO-IP LATIN]

Common Name

English

TRIDONE

Common Name

English

3,5,5-Trimethyl-2,4-oxazolidinedione

Systematic Name

English

NSC-169503

Code

English

TROXIDONE

Common Name

English

trimethadione [INN]

Common Name

English

Trimethadione [WHO-DD]

Common Name

English

TRIMETHADIONE [VANDF]

Common Name

English

TRIDIONE

Brand Name

English

TRIMETHADIONE [JAN]

Common Name

English

MINOALEVIATIN

Common Name

English

2,4-OXAZOLIDINEDIONE, 3,5,5-TRIMETHYL-

Systematic Name

English

TRIMETHADIONE [MART.]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008486