Identification

Name
Trimethadione
Accession Number
DB00347
Description

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
Thumb
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.

Associated Conditions
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AVoltage-dependent T-type calcium channel subunit alpha-1G
inhibitor
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

90%

Metabolism

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Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
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Toxicity

Symptoms of overdose include clumsiness or unsteadiness, coma, dizziness (severe), drowsiness (severe), nausea (severe), and problems with vision.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbametapirThe serum concentration of Trimethadione can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Trimethadione can be increased when combined with Abatacept.
AbirateroneThe metabolism of Trimethadione can be decreased when combined with Abiraterone.
AcarboseThe risk or severity of hypoglycemia can be increased when Trimethadione is combined with Acarbose.
AcebutololThe risk or severity of bradycardia can be increased when Trimethadione is combined with Acebutolol.
AceclofenacThe risk or severity of hyperkalemia can be increased when Trimethadione is combined with Aceclofenac.
AcemetacinThe risk or severity of hyperkalemia can be increased when Trimethadione is combined with Acemetacin.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Trimethadione.
AcetaminophenTrimethadione may increase the hepatotoxic activities of Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Trimethadione is combined with Acetazolamide.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol. The combination of alcohol with trimethadione may make you sleepy or dizzy.

Products

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International/Other Brands
Minoale (Dainippon Sumitomo)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TridioneTablet, chewable150 mg/1OralAbbVie Inc.1946-01-252020-04-12US flag
Additional Data Available
  • Application Number
    Application Number
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    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N03AC02 — Trimethadione
Drug Categories
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

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
Human Metabolome Database
HMDB0014491
KEGG Drug
D00392
PubChem Compound
5576
PubChem Substance
46504478
ChemSpider
5374
BindingDB
50227239
RxNav
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
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
Packagers
  • Abbott Laboratories Ltd.
Dosage Forms
FormRouteStrength
Tablet, chewableOral150 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)46 °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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (7.69 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4l-8900000000-43db0866b0f6797cbff6
GC-MS Spectrum - CI-BGC-MSsplash10-0006-1900000000-5560efcfc7260e1dcfef
Mass Spectrum (Electron Ionization)MSsplash10-0006-9200000000-46082deb9c636fb8f625
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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
  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
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
  1. 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]
  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
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
  1. 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]
  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
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
  1. 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
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
  1. 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]
  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
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
  1. 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]
  2. 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. [PubMed:11896285]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2020 03:00

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