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Record Information
Version2.0
Creation Date2009-07-21 20:27:16 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2839
Identification
Common NameParamethadione
ClassSmall Molecule
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.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Paradione
Parametadiona
Parametadione
Paramethadionum
Chemical FormulaC7H11NO3
Average Molecular Mass157.167 g/mol
Monoisotopic Mass157.074 g/mol
CAS Registry Number115-67-3
IUPAC Name5-ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione
Traditional Nameparamethadione
SMILESCCC1(C)OC(=O)N(C)C1=O
InChI IdentifierInChI=1/C7H11NO3/c1-4-7(2)5(9)8(3)6(10)11-7/h4H2,1-3H3
InChI KeyInChIKey=VQASKUSHBVDKGU-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as oxazolidinediones. Oxazolidinediones are compounds containing an oxazolidine ring which bears two ketones.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassOxazolidines
Direct ParentOxazolidinediones
Alternative Parents
Substituents
  • Oxazolidinedione
  • Dicarboximide
  • Carbamic acid ester
  • Carbonic acid derivative
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxide
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling Point101.5°C
Solubility8.4 mg/mL
LogP0.3
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 KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-6900000000-cb5c4b22a5f6eea03ccbJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-6d7437f8325dda84507aJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-6900000000-cb5c4b22a5f6eea03ccbJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-6d7437f8325dda84507aJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05di-9300000000-2eb214bab933a55ae037JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-1900000000-939447f74cc7e7a8684eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0kmi-9300000000-38031d50b903ad7c6498JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pb9-9000000000-1e13dc003e64f9bfbd19JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-f6573876063f4b2e67d3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-3900000000-9323279d26818d446640JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-6b6057da57118121825eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-2900000000-a394c98603a9a56e9f0cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9300000000-383936e98ff88b856301JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-41adabf4781a72bfc85fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-6bfe1fe3bf97bb99356dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bt9-8900000000-d20643ca1c05d11031f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pvi-9300000000-7eb87c0cc4c9749b272dJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0006-9300000000-5b8273da08cb63d81fcfJSpectraViewer | MoNA
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureRapid via the digestive tract.
Mechanism of ToxicityDione 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.
MetabolismPrimarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite. Half Life: 12 to 24 hours (however the half-life for the active metabolite is not known)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed for the control of absence (petit mal) seizures that are refractory to treatment with other medications.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00617
HMDB IDHMDB14755
PubChem Compound ID8280
ChEMBL IDCHEMBL1100
ChemSpider ID7979
KEGG IDC07411
UniProt IDNot Available
OMIM ID
ChEBI ID250989
BioCyc IDNot Available
CTD IDNot Available
Stitch IDParamethadione
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkParamethadione
References
Synthesis ReferenceNot Available
MSDST3D2839.pdf
General References
  1. 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. [1185541 ]
  2. 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. [412416 ]
  3. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated calcium 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 (By similarity).
Gene Name:
CACNA1I
Uniprot ID:
Q9P0X4
Molecular Weight:
245100.8 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. [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. [17016423 ]