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Record Information
Version4.0
Creation Date2012-09-06 15:16:50 UTC
Update Date2017-09-27 08:27:41 UTC
HMDB IDHMDB0014755
Secondary Accession Numbers
  • HMDB14755
Metabolite Identification
Common NameParamethadione
DescriptionParamethadione is only found in individuals that have used or taken this drug. It is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.
Structure
Thumb
Synonyms
ValueSource
ParadioneKegg
5-Ethyl-3,5-dimethyloxazolinedioneMeSH
Chemical FormulaC7H11NO3
Average Molecular Weight157.1671
Monoisotopic Molecular Weight157.073893223
IUPAC Name5-ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione
Traditional Nameparamethadione
CAS Registry Number115-67-3
SMILES
CCC1(C)OC(=O)N(C)C1=O
InChI Identifier
InChI=1S/C7H11NO3/c1-4-7(2)5(9)8(3)6(10)11-7/h4H2,1-3H3
InChI KeyVQASKUSHBVDKGU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as oxazolidinediones. These are compounds containing an oxazolidine ring which bears two ketones.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassAzolidines
Direct ParentOxazolidinediones
Alternative Parents
Substituents
  • Oxazolidinedione
  • Carbamic acid ester
  • Dicarboximide
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

Indirect biological role:

Physiological effect

Health effect:

  Health condition:

    Gastrointestinal disorders:

  Observation:

Physical Properties
StateLiquid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling Point101.5 °CNot Available
Water Solubility135 g/LNot Available
LogP0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility135 g/LALOGPS
logP0.9ALOGPS
logP1.03ChemAxon
logS-0.07ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area46.61 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity37.72 m³·mol⁻¹ChemAxon
Polarizability15.39 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-6900000000-cb5c4b22a5f6eea03ccbView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-6d7437f8325dda84507aView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05di-9300000000-2eb214bab933a55ae037View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-1900000000-939447f74cc7e7a8684eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0kmi-9300000000-38031d50b903ad7c6498View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pb9-9000000000-1e13dc003e64f9bfbd19View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-f6573876063f4b2e67d3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-3900000000-9323279d26818d446640View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-6b6057da57118121825eView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0006-9300000000-5b8273da08cb63d81fcfView in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00617 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00617 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-6 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-3 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00617
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID7979
KEGG Compound IDC07411
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkParamethadione
METLIN IDNot Available
PubChem Compound8280
PDB IDNot Available
ChEBI ID250989
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Feldman GL, Weaver DD, Lovrien EW: The fetal trimethadione syndrome: report of an additional family and further delineation of this syndrome. Am J Dis Child. 1977 Dec;131(12):1389-92. [PubMed:412416 ]
  2. Hoffman DJ, Chun AH: Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose. J Pharm Sci. 1975 Oct;64(10):1702-3. [PubMed:1185541 ]

Enzymes

General function:
Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
General function:
Involved in monooxygenase 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, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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 ]
General function:
Involved in monooxygenase 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
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. Tanaka E, Terada M, Misawa S: Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther. 2000 Jun;25(3):165-75. [PubMed:10886461 ]
General function:
Involved in monooxygenase 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 responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
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 ]
General function:
Involved in ion channel activity
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. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and 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. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H
Gene Name:
CACNA1I
Uniprot ID:
Q9P0X4
Molecular weight:
245100.8
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 ]