Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:13 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2834
Identification
Common NameEthosuximide
ClassSmall Molecule
DescriptionEthosuximide is only found in individuals that have used or taken this drug. It is an anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures. [PubChem]Binds to T-type voltage sensitive calcium channels. 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.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Drug
  • Metabolite
  • Organic Compound
  • Succinimide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-2-Ethyl-2-methylsuccinimide
(±)-2-ethyl-2-methylsuccinimide
2-ethyl-2-methylsuccinimide
2-Methyl-2-ethylsuccinimide
3-ethyl-3-methyl-2,5-pyrrolidinedione
3-Ethyl-3-methylsuccinimide
3-Methyl-3-ethylpyrrolidine-2,5-dione
3-Methyl-3-ethylsuccinimide
Aethosuximide
alpha-Ethyl-alpha-methylsuccinimide
alpha-Methyl-alpha-ethylsuccinimide
Atysmal
Emeside
Ethosuccimide
Ethosuccinimide
Ethosuxide
Ethosuximid
Ethosuximidum
Ethymal
Etosuximida
Etoxin
gamma-Ethyl-gamma-methyl-succinimide
gamma-Methyl-gamma-ethyl-succinimide
Petimid
Petinimid
Petnidan
Suxilep
Suxinutin
Thilopemal
Zarondan
Zarontin
γ-ethyl-γ-methyl-succinimide
Chemical FormulaC7H11NO2
Average Molecular Mass141.168 g/mol
Monoisotopic Mass141.079 g/mol
CAS Registry Number77-67-8
IUPAC Name3-ethyl-3-methylpyrrolidine-2,5-dione
Traditional Nameethosuximide
SMILESCCC1(C)CC(O)=NC1=O
InChI IdentifierInChI=1/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
InChI KeyInChIKey=HAPOVYFOVVWLRS-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrrolidine-2-ones. These are pyrrolidines which bear a C=O group at position 2 of the pyrrolidine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolidines
Sub ClassPyrrolidones
Direct ParentPyrrolidine-2-ones
Alternative Parents
Substituents
  • 2-pyrrolidone
  • Carboxylic acid imide
  • Dicarboximide
  • Carboxylic acid imide, n-unsubstituted
  • Lactam
  • Carboxylic acid derivative
  • Azacycle
  • Carbonyl group
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • 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
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point64.5°C
Boiling PointNot Available
Solubility39.2 g/L
LogP0.38
Predicted Properties
PropertyValueSource
Water Solubility101 g/LALOGPS
logP0.1ALOGPS
logP0.55ChemAxon
logS-0.15ALOGPS
pKa (Strongest Acidic)10.73ChemAxon
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.17 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity35.96 m³·mol⁻¹ChemAxon
Polarizability14.45 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)splash10-08mi-9400000000-44583cdc88d3203a4e84View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0006-1900000000-1c27ada66f7846f9d155View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0006-2900000000-19e57defe9ded4ed42b4View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-08mi-9400000000-44583cdc88d3203a4e84View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0006-1900000000-1c27ada66f7846f9d155View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0006-2900000000-19e57defe9ded4ed42b4View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-056r-9300000000-85b98f89652d40beec08View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0900000000-86a82d1f0e8a43f11ab5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-006x-3900000000-e43cf4042ca22cb5d6a8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0q29-9000000000-0593295be197f643992cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-1900000000-7b6a825d9781021fd166View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-3900000000-a161e0f30f683c657129View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6x-9000000000-25a91a77a1c19188305eView in MoNA
MSMass Spectrum (Electron Ionization)splash10-08mi-9300000000-3d87944377ee1f85803dView in MoNA
Toxicity Profile
Route of ExposureBioavailability following oral administration is 93%.
Mechanism of ToxicityBinds to T-type voltage sensitive calcium channels. 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.
MetabolismHepatic, via CYP3A4 and CYP2E1. Half Life: 53 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of petit mal epilepsy.
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.
SymptomsAcute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression.
TreatmentTreatment should include emesis (unless the patient is or could rapidly become obtunded, comatose, or convulsing) or gastric lavage, activated charcoal, cathartics, and general supportive measures. Hemodialysis may be useful to treat ethosuximide overdose. Forced diuresis and exchange transfusions are ineffective. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00593
HMDB IDHMDB14731
PubChem Compound ID3291
ChEMBL IDCHEMBL696
ChemSpider ID3175
KEGG IDC07505
UniProt IDNot Available
OMIM ID
ChEBI ID4887
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEthosuximide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEthosuximide
References
Synthesis Reference

Miller, C.A. and Long, L.M.; U.S. Patent 2,993,835; July 25,1961; assigned to Parke, Davis and Company.

MSDSLink
General References
  1. Patsalos PN: Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies. Epilepsia. 2005;46 Suppl 9:140-8. [16302888 ]
  2. Coulter DA, Huguenard JR, Prince DA: Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons. Neurosci Lett. 1989 Mar 13;98(1):74-8. [2710401 ]
  3. Coulter DA, Huguenard JR, Prince DA: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol. 1989 Jun;25(6):582-93. [2545161 ]
  4. Coulter DA, Huguenard JR, Prince DA: Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction. Br J Pharmacol. 1990 Aug;100(4):800-6. [2169941 ]
  5. Kostyuk PG, Molokanova EA, Pronchuk NF, Savchenko AN, Verkhratsky AN: Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons. Neuroscience. 1992 Dec;51(4):755-8. [1336826 ]
  6. Drugs.com [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50240424
References
  1. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
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-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel 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.
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>5000 uMNot AvailableBindingDB 50240424
References
  1. Yang ZQ, Barrow JC, Shipe WD, Schlegel KA, Shu Y, Yang FV, Lindsley CW, Rittle KE, Bock MG, Hartman GD, Uebele VN, Nuss CE, Fox SV, Kraus RL, Doran SM, Connolly TM, Tang C, Ballard JE, Kuo Y, Adarayan ED, Prueksaritanont T, Zrada MM, Marino MJ, Graufelds VK, DiLella AG, Reynolds IJ, Vargas HM, Bunting PB, Woltmann RF, Magee MM, Koblan KS, Renger JJ: Discovery of 1,4-substituted piperidines as potent and selective inhibitors of T-type calcium channels. J Med Chem. 2008 Oct 23;51(20):6471-7. doi: 10.1021/jm800830n. Epub 2008 Sep 26. [18817368 ]