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
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
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 |
---|---|---|---|
Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16171802 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TRIDIONE Approved UseINDICATIONS TRIDIONE (trimethadione) is indicated for the control of petit mal seizures that are refractory to treatment with other drugs. Launch Date1946 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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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 |
T1/2
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: |
unhealthy, 16 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 16 years Sex: M Population Size: 1 Sources: |
Disc. AE: Hepatitis... AEs leading to discontinuation/dose reduction: Hepatitis (1 patient) Sources: |
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: |
unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: |
Disc. AE: Aplastic anemia... AEs leading to discontinuation/dose reduction: Aplastic anemia (grade 5, 1 patient) Sources: |
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: |
unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: |
Disc. AE: Agranulocytosis, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Agranulocytosis (grade 5, 1 patient) Sources: Thrombocytopenia (grade 5, 1 patient) |
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: |
unhealthy n = 1 Health Status: unhealthy Condition: tetanus Sex: M Population Size: 1 Sources: |
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: |
unhealthy, 16 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 16 years Sex: M Population Size: 1 Sources: |
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: |
unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: |
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: |
unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: |
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: |
unhealthy, 23 years n = 1 Health Status: unhealthy Condition: petit mal seizures Age Group: 23 years Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
inconclusive | ||||
Page: 7.0 |
likely | |||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Pharmacologic interactions of albutoin with other anticonvulsant drugs. | 1970 Aug |
|
Possible teratogenicity of trimethadione and paramethadione. | 1970 Aug 1 |
|
Fetal anomalies following maternal trimethadione ingestion. | 1973 May |
|
The fetal trimethadione syndrome. | 1975 Aug |
|
Measurement of anticonvulsant activity in the Papio papio model of epilepsy. | 1976 Sep |
|
[Quantitative analysis of conditional-optimal doses of succilep and trimetin in the treatment of children and adolescents with minor forms of epilepsy]. | 1977 |
|
Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect. | 1978 Feb |
|
Phenotypic malformations in association with maternal trimethadione therapy. | 1978 Feb |
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Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin. | 1980 Nov 28 |
|
Comparison of the actions of trimethadione and chlordiazepoxide in animal models of anxiety and benzodiazepine receptor binding. | 1982 Nov |
|
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 |
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Only certain antiepileptic drugs prevent seizures induced by pilocarpine. | 1987 Jul |
|
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 |
|
Anticonvulsants for soman-induced seizure activity. | 1999 Mar-Apr |
|
[Fetal trimethadione syndrome]. | 2001 |
|
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. | 2001 Dec |
|
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 |
|
Determination of trimetazidine HCl by adsorptive stripping square-wave voltammetry at a glassy carbon electrode. | 2002 Jan 1 |
|
Embryonic arrhythmia by inhibition of HERG channels: a common hypoxia-related teratogenic mechanism for antiepileptic drugs? | 2002 May |
|
Postnatal closure of membranous ventricular septal defects in Sprague-Dawley rat pups after maternal exposure with trimethadione. | 2004 Jun |
|
The history of barbiturates a century after their clinical introduction. | 2005 Dec |
|
The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil. | 2005 Oct 3 |
|
Effects of anticonvulsant drugs on life span. | 2006 Apr |
|
Classification and diagnosis of ear malformations. | 2007 |
|
Treatment of Lennox-Gastaut syndrome: overview and recent findings. | 2008 Dec |
|
Etiology of congenital dislocation of the hip : Carl E. Badgley MD (1893-1973). The 11th president of the AAOS 1942. | 2008 Jan |
|
Valproic acid extends Caenorhabditis elegans lifespan. | 2008 Jun |
|
Allyl isothiocyanate that induces GST and UGT expression confers oxidative stress resistance on C. elegans, as demonstrated by nematode biosensor. | 2010 Feb 17 |
|
Zebrafish (Danio rerio) embryos as a model for testing proteratogens. | 2011 Mar 15 |
Patents
Sample Use Guides
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
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000008486
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WHO-ATC |
N03AC02
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NDF-RT |
N0000175753
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NCI_THESAURUS |
C264
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2751
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7316
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TRIMETHADIONE
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PRIMARY | Description: Colourless, granular crystals; odour, slightly camphoraceous. Solubility: Soluble in water; freely soluble in ethanol (~750 g/l) TS and ether R. Category: Anticonvulsant. Storage: Trimethadione should be kept in a well-closed container. Definition: Trimethadione contains not less than 98.0% and not more than 101.0% of C6H9NO3, calculated with reference to the dried substance. | ||
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Trimethadione
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m11145
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DB00347
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C47772
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CHEMBL695
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ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)