You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameTrimethadione
Accession NumberDB00347  (APRD00315)
TypeSmall Molecule
GroupsApproved
Description

An anticonvulsant effective in absence seizures, but generally reserved for refractory cases because of its toxicity. (From AMA Drug Evaluations Annual, 1994, p378)

Structure
Thumb
Synonyms
Tridione
Trimethadion
Triméthadione
Trimethadionum
Trimethinum
Troxidone
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tridionetablet, chewable150 mg/1oralAbb Vie Inc.1946-01-25Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MinoaleDainippon Sumitomo
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIR7GV3H6FQ4
CAS number127-48-0
WeightAverage: 143.1406
Monoisotopic: 143.058243159
Chemical FormulaC6H9NO3
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oxazolidinediones. These are compounds containing an oxazolidine ring which bears two ketones.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassOxazolidines
Direct ParentOxazolidinediones
Alternative Parents
Substituents
  • Oxazolidinedione
  • Tertiary amine
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed in the control of absence (petit mal) seizures that are refractory to treatment with other medications.
PharmacodynamicsParamethadione 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 actionDione 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding90%
Metabolism
SubstrateEnzymesProduct
Trimethadione
dimethadioneDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose include clumsiness or unsteadiness, coma, dizziness (severe), drowsiness (severe), nausea (severe), and problems with vision.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.9479
Caco-2 permeable+0.5287
P-glycoprotein substrateNon-substrate0.8304
P-glycoprotein inhibitor INon-inhibitor0.6154
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.9503
CYP450 2C9 substrateNon-substrate0.8289
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5881
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9694
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9361
Ames testNon AMES toxic0.6493
CarcinogenicityNon-carcinogens0.8515
BiodegradationNot ready biodegradable0.7859
Rat acute toxicity1.8563 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9961
hERG inhibition (predictor II)Non-inhibitor0.9775
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
Packagers
Dosage forms
FormRouteStrength
Tablet, chewableoral150 mg/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point46 °CPhysProp
water solubility5E+004 mg/LMERCK INDEX (1996)
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility212.0 mg/mLALOGPS
logP0.07ALOGPS
logP0.5ChemAxon
logS0.17ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area46.61 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity33.2 m3·mol-1ChemAxon
Polarizability13.59 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.69 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-0006-9200000000-46082deb9c636fb8f625View in MoNA
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN03AC02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
MefloquineThe therapeutic efficacy of Trimethadione can be decreased when used in combination with Mefloquine.
OrlistatThe serum concentration of Trimethadione can be decreased when it is combined with Orlistat.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-v...
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. 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. [PubMed:17016423 ]
  3. 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. [PubMed:17291698 ]
  4. 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. [PubMed:16171802 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
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 or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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. [PubMed:14651673 ]
  3. 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. [PubMed:9879636 ]
Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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. [PubMed:14651673 ]
  3. 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. [PubMed:9879636 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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. [PubMed:9879636 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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. [PubMed:14651673 ]
  3. 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. [PubMed:9879636 ]
Kind
Protein
Organism
Human
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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. [PubMed:9879636 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23