Trimethadione
Identification
- Summary
Trimethadione is an anticonvulsant agent indicated for the control of treatment-refractory petit mal seizures.
- Generic Name
- Trimethadione
- DrugBank Accession Number
- DB00347
- Background
An anticonvulsant effective in absence seizures, but generally reserved for refractory cases because of its toxicity. (From AMA Drug Evaluations Annual, 1994, p378)
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 143.1406
Monoisotopic: 143.058243159 - Chemical Formula
- C6H9NO3
- Synonyms
- Trimetadiona
- Trimethadion
- Triméthadione
- Trimethadione
- Trimethadionum
- Trimethinum
- Troxidone
- External IDs
- A 2297
- J2.519D
- NSC-15799
- NSC-169503
Pharmacology
- Indication
Used in the control of absence (petit mal) seizures that are refractory to treatment with other medications.
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- Pharmacodynamics
Paramethadione and trimethadione are anticonvulsants indicated in the control of absence (petit mal) seizures that are refractory to treatment with other medications. Dione anticonvulsants are used in the treatment of epilepsy. They act on the central nervous system (CNS) to reduce the number of seizures.
- Mechanism of action
Dione anticonvulsants reduce T-type calcium currents in thalamic neurons, including thalamic relay neurons. It does so via the inhibition of voltage dependent T-type calcium channels. This raises the threshold for repetitive activity in the thalamus, and inhibits corticothalamic transmission. Thus, the abnormal thalamocortical rhythmicity, which is thought to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram(EEG) with absence seizures, is dampened.
Target Actions Organism AVoltage-dependent T-type calcium channel subunit alpha-1G inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
90%
- Metabolism
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose include clumsiness or unsteadiness, coma, dizziness (severe), drowsiness (severe), nausea (severe), and problems with vision.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Trimethadione is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Trimethadione can be increased when it is combined with Abametapir. Abatacept The metabolism of Trimethadione can be increased when combined with Abatacept. Abiraterone The metabolism of Trimethadione can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Trimethadione. - Food Interactions
- Avoid alcohol. The combination of alcohol with trimethadione may make you sleepy or dizzy.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Minoale (Dainippon Sumitomo)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tridione Tablet, chewable 150 mg/1 Oral AbbVie Inc. 1946-01-25 2020-04-12 US
Categories
- ATC Codes
- N03AC02 — Trimethadione
- Drug Categories
- Agents causing hyperkalemia
- Anti-epileptic Agent
- Antiarrhythmic agents
- Anticonvulsants
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Decreased Central Nervous System Disorganized Electrical Activity
- Nervous System
- Oxazoles
- Oxazolidine Derivatives
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oxazolidinediones. These are compounds containing an oxazolidine ring which bears two ketones.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azolidines
- Sub Class
- Oxazolidines
- Direct Parent
- Oxazolidinediones
- Alternative Parents
- Dicarboximides / Carbamate esters / Organic carbonic acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic heteromonocyclic compound / Azacycle / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- R7GV3H6FQ4
- CAS number
- 127-48-0
- InChI Key
- IRYJRGCIQBGHIV-UHFFFAOYSA-N
- InChI
- InChI=1S/C6H9NO3/c1-6(2)4(8)7(3)5(9)10-6/h1-3H3
- IUPAC Name
- trimethyl-1,3-oxazolidine-2,4-dione
- SMILES
- CN1C(=O)OC(C)(C)C1=O
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014491
- KEGG Drug
- D00392
- PubChem Compound
- 5576
- PubChem Substance
- 46504478
- ChemSpider
- 5374
- BindingDB
- 50227239
- 10827
- ChEBI
- 9727
- ChEMBL
- CHEMBL695
- ZINC
- ZINC000001530710
- Therapeutic Targets Database
- DAP001265
- PharmGKB
- PA164744924
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Trimethadione
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Abbott laboratories pharmaceutical products div
- Packagers
- Abbott Laboratories Ltd.
- Dosage Forms
Form Route Strength Tablet, chewable Oral 150 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 46 °C PhysProp water solubility 5E+004 mg/L MERCK INDEX (1996) logP 0 Not Available - Predicted Properties
Property Value Source Water Solubility 212.0 mg/mL ALOGPS logP 0.07 ALOGPS logP 0.5 Chemaxon logS 0.17 ALOGPS Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 46.61 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 33.2 m3·mol-1 Chemaxon Polarizability 13.59 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9954 Blood Brain Barrier + 0.9479 Caco-2 permeable + 0.5287 P-glycoprotein substrate Non-substrate 0.8304 P-glycoprotein inhibitor I Non-inhibitor 0.6154 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.9503 CYP450 2C9 substrate Non-substrate 0.8289 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.5881 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.9694 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9361 Ames test Non AMES toxic 0.6493 Carcinogenicity Non-carcinogens 0.8515 Biodegradation Not ready biodegradable 0.7859 Rat acute toxicity 1.8563 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9961 hERG inhibition (predictor II) Non-inhibitor 0.9775
Spectra
- Mass Spec (NIST)
- Download (7.69 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 128.2779922 predictedDarkChem Lite v0.1.0 [M-H]- 128.1809922 predictedDarkChem Lite v0.1.0 [M-H]- 124.12627 predictedDeepCCS 1.0 (2019) [M+H]+ 128.7643922 predictedDarkChem Lite v0.1.0 [M+H]+ 128.7673922 predictedDarkChem Lite v0.1.0 [M+H]+ 127.570404 predictedDeepCCS 1.0 (2019) [M+Na]+ 128.5216922 predictedDarkChem Lite v0.1.0 [M+Na]+ 136.53941 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Scaffold protein binding
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
- Gene Name
- CACNA1G
- Uniprot ID
- O43497
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1G
- Molecular Weight
- 262468.62 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Shen H, Zhang B, Shin JH, Lei D, Du Y, Gao X, Wang Q, Ohlemiller KK, Piccirillo J, Bao J: Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60. Epub 2006 Dec 31. [Article]
- Barton ME, Eberle EL, Shannon HE: The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil. Eur J Pharmacol. 2005 Oct 3;521(1-3):79-85. Epub 2005 Sep 19. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Tanaka E, Kurata N, Yasuhara H: Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes. J Clin Pharm Ther. 2003 Dec;28(6):493-6. [Article]
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Tanaka E, Kurata N, Yasuhara H: Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes. J Clin Pharm Ther. 2003 Dec;28(6):493-6. [Article]
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Tanaka E, Kurata N, Yasuhara H: Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes. J Clin Pharm Ther. 2003 Dec;28(6):493-6. [Article]
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Ginsberg G, Hattis D, Sonawane B, Russ A, Banati P, Kozlak M, Smolenski S, Goble R: Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci. 2002 Apr;66(2):185-200. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:40