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Identification
Name Trimethadione
Accession Number DB00347 (APRD00315)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Trimetadione
Trimethadion
Trimethdione
Salts Not Available
Brand names
Name Company
Absentol
Absetil
Convenixa
Convexina
Edion
Epidione
Epidone
Epixal
Etydion
Mino-Aleviatin
Minoaleuiatin
Minoaleviatin
Neo-Absentol
Petidion
Petidon
Petilep
Petimalin
Pitmal
Ptimal
Tioxanona
Tredione
Tricione
Tridilona
Tridion
Tridione
Tridone
Trilidona
Trimedal
Trimedone
Trimethin
Trimetin
Trioxanona
Triozanona
Tromedone
Troxidone
First Prev Next Last
Brand mixtures Not Available
Categories
  • Anticonvulsants
CAS number 127-48-0
Weight Average: 143.1406
Monoisotopic: 143.058243159
Chemical Formula C6H9NO3
InChI Key InChIKey=IRYJRGCIQBGHIV-UHFFFAOYSA-N
InChI
InChI=1S/C6H9NO3/c1-6(2)4(8)7(3)5(9)10-6/h1-3H3
Plain Text
IUPAC Name
trimethyl-1,3-oxazolidine-2,4-dione
SMILES
CN1C(=O)OC(C)(C)C1=O
Plain Text
Mass Spec show (7.69 KB)
Taxonomy
Kingdom Organic
Classes
  • Carbamates and Derivatives
  • Oxazolidinones
Substructures
  • Carbamates and Derivatives
  • Amino Ketones
  • Ethers
  • Oxazolidinones
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Carboxylic Acids and Derivatives
Pharmacology
Indication Used in the control of absence (petit mal) seizures that are refractory to treatment with other medications.
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.
Absorption Not Available
Volume of distribution Not Available
Protein binding 90%
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
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
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
Packagers
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 46 °C PhysProp
water solubility 5E+004 mg/L MERCK INDEX (1996)
logP 0 Not Available
Predicted Properties
Property Value Source
water solubility 2.12e+02 g/l 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 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 33.2 ChemAxon
polarizability 13.59 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00392 Link_out
PubChem Compound 5576 Link_out
PubChem Substance 46504478 Link_out
ChemSpider 5374 Link_out
BindingDB 50019167 Link_out
Therapeutic Targets Database DAP001265 Link_out
PharmGKB PA164744924 Link_out
Drugs.com http://www.drugs.com/mtm/trimethadione.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Trimethadione Link_out
ATC Codes
  • N03AC02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Disulfiram Disulfiram, a strong CYP2E1 inhibitor, may decrease the metabolism and clearance of Trimethadione, a CYP2E1 substrate. Consider alternate therapy or monitor for changes in Trimethadione therapeutic and adverse effects if Disulfiram is initiated, discontinued or dose changed.
Triprolidine The CNS depressants, Triprolidine and Trimethadione, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions Not Available
Targets

1. Voltage-dependent T-type calcium channel subunit alpha-1G

Pharmacological action: yes
Actions: inhibitor

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-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes

Organism class: human
UniProt ID: O43497 Link_out
Gene: CACNA1G Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: substrate

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

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  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
  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

2. Cytochrome P450 3A4

Actions: substrate

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  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
  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

3. Cytochrome P450 2C8

Actions: substrate

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 responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  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

4. Cytochrome P450 2C9

Actions: substrate

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  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
  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

5. Cytochrome P450 2C19

Actions: substrate

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19