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 19 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16171802	Blocker 555

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 8583	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 1946

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 Sources: https://pubmed.ncbi.nlm.nih.gov/13760024	unhealthy, 16 years Health Status: unhealthy Age Group: 16 years Sex: M 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 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 Health Status: unhealthy Age Group: 23 years Sex: F 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 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 Health Status: unhealthy Age Group: 23 years Sex: F 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 Health Status: unhealthy Sex: M 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 Sources: https://pubmed.ncbi.nlm.nih.gov/13760024	unhealthy, 16 years Health Status: unhealthy Age Group: 16 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/13760024
Aplastic anemia	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: 23 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
Agranulocytosis	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: 23 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/20995214
Thrombocytopenia	grade 5, 1 patient Disc. AE	0.3 g 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: 23 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/20995214

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
T-type Ca2+ channels 3 Ca2+ channels 59	CYP 303 CYP1A2 1197 CYP2E1 729

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 62	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25256602/	yes
T-type Ca2+ channels 3	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16171802/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	inconclusive
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/005856s021lbl.pdf Page: 7.0	likely
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	yes
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14651673/; https://pubmed.ncbi.nlm.nih.gov/9879636/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9375358/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
Aaron Chemicals	AR000X7U	http://www.aaronchem.com/127-48-0
abcr GmbH	AB133755	http://www.abcr.com/shop/en/AB133755
AbMole Bioscience	M6038	http://www.abmole.com/products/trimethadione.html
Achemica	ACMC-1BYOW	http://www.achemica.com/prodinfo/?id=75259
AHH Chemical co.,ltd	MT-37010	http://www.ahhchemical.com/product/MT-37010.html
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
BioSynth	J-005496	https://www.biosynth.com/en/products/all-products/products/J-005496.html
BLD Pharm	BD82238	http://www.bldpharm.com/products/127-48-0.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
CSNpharm	CSN19336	https://www.csnpharm.com/products/trimethadione.html
DC Chemicals	DC31900	http://www.dcchemicals.com//product_show-Tridione.html
eNovation Chemicals	D673674	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673674
Finetech	FT-0694585	http://www.finetechnology-ind.com/prod/detail/pub/127-48-0.html
iChemical	EBD71235	http://www.ichemical.com/products/127-48-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN01303924	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01303924
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
mcule	MCULE-4761457520	https://mcule.com/MCULE-4761457520
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	1690000_USP	https://www.sigmaaldrich.com/catalog/product/usp/1690000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
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
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

PubMed

Title	Date	PubMed
Zebrafish (Danio rerio) embryos as a model for testing proteratogens.	2011-03-15	21237239
Allyl isothiocyanate that induces GST and UGT expression confers oxidative stress resistance on C. elegans, as demonstrated by nematode biosensor.	2010-02-17	20174640
Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.	2010-02	19430925
Neuroprotective effects of blockers for T-type calcium channels.	2009-10-28	19863782
Treatment of Lennox-Gastaut syndrome: overview and recent findings.	2008-12	19337447
The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan.	2008-10	18949032
Valproic acid extends Caenorhabditis elegans lifespan.	2008-06	18248662
Effect of optical flow versus attentional strategy on gait in Parkinson's Disease: a study with a portable optical stimulating device.	2008-01-18	18205903
Etiology of congenital dislocation of the hip : Carl E. Badgley MD (1893-1973). The 11th president of the AAOS 1942.	2008-01	18196378
Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss.	2007-04	17291698
Classification and diagnosis of ear malformations.	2007	22073081
The ethics of excluding women who become pregnant while participating in clinical trials of anti-epileptic medications.	2006-12	17011799
Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans.	2006-10	16872777
Education and imaging. Hepatobiliary and pancreatic: oral therapy for pancreatic duct stones.	2006-09	16911703
Effects of anticonvulsant drugs on life span.	2006-04	16606760
The history of barbiturates a century after their clinical introduction.	2005-12	18568113
The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil.	2005-10-03	16171802
Oral litholysis therapy for endoscopically unretrievable obstructive pancreatic stones.	2005-05	15841053
Adulteration of South African traditional herbal remedies.	2005-02	15665751
Anticonvulsant medications extend worm life-span.	2005-01-14	15653505
Postnatal closure of membranous ventricular septal defects in Sprague-Dawley rat pups after maternal exposure with trimethadione.	2004-06	15282739
Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes.	2003-12	14651673
Embryonic arrhythmia by inhibition of HERG channels: a common hypoxia-related teratogenic mechanism for antiepileptic drugs?	2002-05	12027905
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.	2001-12	11738929
Characterization of the antiabsence effects of SCH 50911, a GABA-B receptor antagonist, in the lethargic mouse, gamma-hydroxybutyrate, and pentylenetetrazole models.	1995-09	7562514
Dissolution of pancreatic stones by oral trimethadione in patients with chronic calcific pancreatitis.	1994-09-01	7827299
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
Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat.	1988-09-01	3137016
Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts.	1988-09	2905779
Only certain antiepileptic drugs prevent seizures induced by pilocarpine.	1987-07	3607518
Fetal anticonvulsant syndrome in rats: effects on postnatal behavior and brain amino acid content.	1985-09-01	4080065
Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat.	1985	3922381
A model of chronic spontaneous petit mal-like seizures in the rat: comparison with pentylenetetrazol-induced seizures.	1984-06	6426943
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.	1983-11	6195326
Comparison of the actions of trimethadione and chlordiazepoxide in animal models of anxiety and benzodiazepine receptor binding.	1982-11	6129593
Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin.	1980-11-28	6254150
Troxidone (trimethadione) embryopathy: case report with reveiw of the literature.	1979	550945
Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect.	1978-02	565846
Phenotypic malformations in association with maternal trimethadione therapy.	1978-02	413897
[Quantitative analysis of conditional-optimal doses of succilep and trimetin in the treatment of children and adolescents with minor forms of epilepsy].	1977	409014
Measurement of anticonvulsant activity in the Papio papio model of epilepsy.	1976-09	821787
Di-n-propylacetic acid--profile of anticonvulsant activity in mice.	1976-02	779804
The fetal trimethadione syndrome.	1975-08	50427
Fetal anomalies following maternal trimethadione ingestion.	1973-05	4572938
Trimethadione (Tridione)-induced nephrotic syndrome. A report of a case with unique ultrastructural renal pathology.	1973-02	4631174
Possible teratogenicity of trimethadione and paramethadione.	1970-08-01	4193708
Pharmacologic interactions of albutoin with other anticonvulsant drugs.	1970-08	5451364
Myasthenia gravis syndrome associated with trimethadione.	1970-06-29	4987393
Successful therapy of trimethadione nephrosis with prednisone and cyclophosphamide. Report of a case.	1967-08	4961747
Nephrotic syndrome caused by probenecid.	1967-01-02	6071127

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 `Mon Mar 31 17:47:30 GMT 2025` Edited by `admin` on `Mon Mar 31 17:47:30 GMT 2025`
Record UNII	R7GV3H6FQ4
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TRIMETHADIONE

Official Name

English

TRIDIONE

Preferred 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

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