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targets (2) transporters (2)
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Identification
Name Levetiracetam
Accession Number DB01202 (APRD01068)
Type small molecule
Groups approved
Description

Levetiracetam 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.
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Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • levetiracetam
  • Levetiracetam [INN]
  • Levetiracetamum [INN-Latin]
  • Levitiracetam
Brand names
  • Keppra
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Nootropic Agents
CAS number 102767-28-2
Weight Average: 170.209
Monoisotopic: 170.105527702
Chemical Formula C8H14N2O2
InChI Key InChIKey=HPHUVLMMVZITSG-ZCFIWIBFSA-N
InChI
InChI=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
Plain Text
IUPAC Name
(2R)-2-(2-oxopyrrolidin-1-yl)butanamide
SMILES
CC[C@@H](N1CCCC1=O)C(N)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Ketones
  • Pyrrolidines
  • Aliphatic and Aryl Amines
  • Gamma Lactams
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Ketones
  • Pyrrolidines
  • Aliphatic and Aryl Amines
  • Carbamates and Derivatives
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Gamma Lactams
  • Lactams
  • Carboxylic Acids and Derivatives
Pharmacology
Indication Used as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.
Pharmacodynamics Not Available
Mechanism of action The 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.
Absorption Rapidly and almost completely absorbed after oral administration (99%). Peak plasma concentrations occurring in about an hour following oral administration in fasted subjects.
Volume of distribution Not Available
Protein binding Very low (<10%)
Metabolism

The 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
Clearance
  • 0.96 mL/min/kg
Toxicity Side effects include aggression, agitation, coma, drowsiness, reduced consciousness, slowed breathing
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ucb inc
  • Nexus pharmaceuticals inc
  • Sun pharmaceutical industries ltd
  • Actavis mid atlantic llc
  • Amneal pharmaceuticals
  • Aurobindo pharma usa inc
  • Cypress pharmaceutical inc
  • Roxane laboratories inc
  • Silarx pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Tolmar inc
  • Wockhardt eu operations (swiss) ag
  • Apotex inc
  • Aurobindo pharma ltd
  • Boca pharmacal inc
  • Cobalt laboratories inc
  • Dr reddys laboratories ltd
  • Invagen pharmaceuticals inc
  • Lupin ltd
  • Methapharm inc
  • Mylan pharmaceuticals inc
  • Orchid healthcare
  • Sandoz inc
  • Solco healthcare us llc
  • Teva pharmaceuticals usa
  • Torrent pharmaceuticals ltd
  • Watson laboratories inc
  • Watson laboratories inc florida
  • Wockhardt ltd
  • Zydus pharmaceuticals usa inc
  • UCB Inc.
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Keppra 500 mg/5 ml vial 9.28 USD ml
Keppra 1000 mg tablet 9.01 USD tablet
Levetiracetam 1000 mg tablet 7.18 USD tablet
Keppra xr 750 mg tablet 6.46 USD tablet
Keppra xr 500 mg tablet 6.43 USD tablet
Keppra 500 mg tablet 5.09 USD tablet
Levetiracetam 750 mg tablet 4.86 USD tablet
Keppra 750 mg tablet 4.74 USD tablet
Keppra XR 500 mg 24 Hour tablet 4.47 USD tablet
Keppra 250 mg tablet 3.62 USD tablet
Levetiracetam 500 mg tablet 3.59 USD tablet
Levetiracetam 250 mg tablet 2.93 USD tablet
Apo-Levetiracetam 750 mg Tablet 1.7 USD tablet
Co Levetiracetam 750 mg Tablet 1.7 USD tablet
Pms-Levetiracetam 750 mg Tablet 1.7 USD tablet
Apo-Levetiracetam 500 mg Tablet 1.23 USD tablet
Co Levetiracetam 500 mg Tablet 1.23 USD tablet
Pms-Levetiracetam 500 mg Tablet 1.23 USD tablet
Apo-Levetiracetam 250 mg Tablet 1.01 USD tablet
Co Levetiracetam 250 mg Tablet 1.01 USD tablet
Pms-Levetiracetam 250 mg Tablet 1.01 USD tablet
Keppra 100 mg/ml Solution 0.95 USD ml
Levetiracetam 100 mg/ml Solution 0.68 USD ml
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP -0.6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.98e+02 g/l ALOGPS
logP -0.64 ALOGPS
logP -0.59 ChemAxon Molconvert
logS 0.24 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 63.40 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 44.08 ChemAxon Molconvert
polarizability 17.78 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00709 Link_out
KEGG Compound C07841 Link_out
PubChem Compound 441341 Link_out
PubChem Substance 46508406 Link_out
ChemSpider 390096 Link_out
Therapeutic Targets Database DAP000502 Link_out
PharmGKB PA450206 Link_out
Drug Product Database 2247028 Link_out
RxList http://www.rxlist.com/cgi/generic3/keppra.htm Link_out
Drugs.com http://www.drugs.com/cdi/levetiracetam.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/kep1561.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Levetiracetam Link_out
ATC Codes
  • N03AX14
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (52.5 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals. Food does not affect bioavailabilty.
Targets

1. Synaptic vesicle glycoprotein 2A

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: Q7L0J3 Link_out
Gene: SV2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B: The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6. Epub 2004 Jun 21. Pubmed
  2. Stahl SM: Psychopharmacology of anticonvulsants: levetiracetam as a synaptic vesicle protein modulator. J Clin Psychiatry. 2004 Sep;65(9):1162-3. Pubmed
  3. Lambeng N, Grossmann M, Chatelain P, Fuks B: Solubilization and immunopurification of rat brain synaptic vesicle protein 2A with maintained binding properties. Neurosci Lett. 2006 May 1;398(1-2):107-12. Epub 2006 Jan 24. Pubmed
  4. Gillard M, Chatelain P, Fuks B: Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. Eur J Pharmacol. 2006 Apr 24;536(1-2):102-8. Epub 2006 Mar 10. Pubmed
  5. Newton HB, Dalton J, Goldlust S, Pearl D: Retrospective analysis of the efficacy and tolerability of levetiracetam in patients with metastatic brain tumors. J Neurooncol. 2007 Sep;84(3):293-6. Epub 2007 Apr 13. Pubmed
  6. Johannessen Landmark C: Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs. 2008;22(1):27-47. Pubmed
  7. 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. Pubmed

2. Voltage-dependent N-type calcium channel subunit alpha-1B

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-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

Organism class: human
UniProt ID: Q00975 Link_out
Gene: CACNA1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  2. Lukyanetz EA, Shkryl VM, Kostyuk PG: Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 2002 Jan;43(1):9-18. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
  2. Luna-Tortos C, Fedrowitz M, Loscher W: Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75. Epub 2008 Sep 11. Pubmed

2. Canalicular multispecific organic anion transporter 1

Actions: substrate

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:47

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.