You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:28:38 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3019
Identification
Common NameLevetiracetam
ClassSmall Molecule
DescriptionLevetiracetam is an anticonvulsant medication used to treat epilepsy. Levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity. Levetiracetam binds to the synaptic vesicle protein SV2A, which is thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to synaptic vesicle protein SV2A is not understood, levetiracetam and related analogs showed a rank order of affinity for SV2A which correlated with the potency of their antiseizure activity in audiogenic seizure-prone mice.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Drug
  • Metabolite
  • Nootropic Agent
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
e Keppra
Keppra
Levetiracetamum
Levetiractam
Levitiracetam
Chemical FormulaC8H14N2O2
Average Molecular Mass170.209 g/mol
Monoisotopic Mass170.106 g/mol
CAS Registry Number102767-28-2
IUPAC Name(2R)-2-(2-oxopyrrolidin-1-yl)butanamide
Traditional Namelevitiracetam
SMILES[H][C@](CC)(N1CCCC1=O)C(O)=N
InChI IdentifierInChI=1S/C8H14N2O2/c1-2-6(8(9)12)10-5-3-4-7(10)11/h6H,2-5H2,1H3,(H2,9,12)/t6-/m1/s1
InChI KeyInChIKey=HPHUVLMMVZITSG-ZCFIWIBFSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Fatty amide
  • Pyrrolidone
  • 2-pyrrolidone
  • Fatty acyl
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Lactam
  • Primary carboxylic acid amide
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.98e+02 g/L
LogP-0.6
Predicted Properties
PropertyValueSource
Water Solubility298 g/LALOGPS
logP-0.64ALOGPS
logP-0.59ChemAxon
logS0.24ALOGPS
pKa (Strongest Acidic)16.09ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.4 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity44.08 m³·mol⁻¹ChemAxon
Polarizability17.78 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002g-9300000000-c7be6e1922b5359940b6JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fb9-0900000000-5d10dc46b3d8459f5136JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-eed0f7c0281298a901e0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-904c39fde7b4a564f4f9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-043119aa2fce9bf106a6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-baaa7247861e2a0c32dcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0900000000-e4d3bcf5f9604374d974JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0fb9-0900000000-c54dadca90f9667c5e5eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-43e7dddd01af30559674JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-bcf3b82b0418f01f7c88JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-af204f882b93928b3786JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-2900000000-0d85e8e75dfd969db153JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-6900000000-8038b6a6542f48ef1db6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0fb9-0900000000-b79c1cd502a80d2cc5a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-b2783da92be1f5956300JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-656f696fd6f22abd3b8cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0900000000-05fe19e5eb84577847c0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-1900000000-b7a6c4f29c539bcb255cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-4900000000-159b3785ab54ec35d7aeJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0900000000-4576e782d08537cb54d3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-7470975ba67c5de6162eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00pl-5900000000-50443438445390c4345aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-517ee6018ae48754d1b7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-ec0076a60bef1bfe06ddJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fb9-2900000000-22b720450ebfea704554JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-17a515534beb406070e0JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureRapidly and almost completely absorbed after oral administration (99%). Peak plasma concentrations occurring in about an hour following oral administration in fasted subjects.
Mechanism of ToxicityThe precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Levetiracetam did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Levetiracetam also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. The predictive value of these animal models for specific types of human epilepsy is uncertain. Levetiracetam is thought to stimulate synaptic vesicle protein 2A (SV2A), inhibiting neurotransmitter release.
MetabolismThe major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. No CYP450 metabolism detected. Route of Elimination: Sixty-six percent (66%) of the dose is renally excreted unchanged. The metabolites have no known pharmacological activity and are renally excreted. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. Half Life: 6-8 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with 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.
SymptomsSide effects include aggression, agitation, coma, drowsiness, reduced consciousness, slowed breathing.
TreatmentThere is no specific antidote for overdose with Levetiracetam. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient's clinical status.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01202
HMDB IDHMDB15333
PubChem Compound ID441341
ChEMBL IDCHEMBL1286
ChemSpider ID390096
KEGG IDC07841
UniProt IDNot Available
OMIM ID
ChEBI ID352567
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLevetiracetam
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLevetiracetam
References
Synthesis Reference

Tooru Futagawa, Jean-Pierre Canvat, Emile Cavoy, Michel Deleers, Michel Hamende, Vincent Zimmermann, “Process for the preparation of levetiracetam.” U.S. Patent US6107492, issued September, 1996.

MSDST3D3019.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
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. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Gene Name:
CACNA1B
Uniprot ID:
Q00975
Molecular Weight:
262493.84 Da
References
  1. De Smedt T, Raedt R, Vonck K, Boon P: Levetiracetam: the profile of a novel anticonvulsant drug-part I: preclinical data. CNS Drug Rev. 2007 Spring;13(1):43-56. [17461889 ]
  2. Lukyanetz EA, Shkryl VM, Kostyuk PG: Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 2002 Jan;43(1):9-18. [11879381 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Transmembrane transporter activity
Specific Function:
Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity).
Gene Name:
SV2A
Uniprot ID:
Q7L0J3
Molecular Weight:
82694.665 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
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. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]