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targets (1) enzymes (3)
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Identification
Name Oxcarbazepine
Accession Number DB00776 (APRD01308)
Type small molecule
Groups approved
Description

Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine – sodium channel inhibition – and is generally used to treat partial seizures in epileptic children and adults.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Oxcarbamazepine
Brand names
  • Trileptal
Brand name mixtures Not Available
Categories
  • Anticonvulsants
CAS number 28721-07-5
Weight Average: 252.268
Monoisotopic: 252.089877638
Chemical Formula C15H12N2O2
InChI Key InChIKey=CTRLABGOLIVAIY-UHFFFAOYSA-N
InChI
InChI=1S/C15H12N2O2/c16-15(19)17-12-7-3-1-5-10(12)9-14(18)11-6-2-4-8-13(11)17/h1-8H,9H2,(H2,16,19)
Plain Text
IUPAC Name
9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide
SMILES
NC(=O)N1C2=C(CC(=O)C3=C1C=CC=C3)C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Dibenzazepines and Derivatives
Substructures
  • Dibenzazepines and Derivatives
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Carbamates and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzoyl Derivatives
  • Anilines
  • Ketones
Pharmacology
Indication For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.
Pharmacodynamics Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.
Mechanism of action The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses.
Absorption Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine.
Volume of distribution
  • 49 L
Protein binding Approximately 40% of the active 10-monohydroxy metabolite (MHD) is bound to serum proteins, predominantly to albumin. Neither oxcarbazepine nor its MHD binds with alpha-1–acid blycoprotein.
Metabolism

Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). MHD is metabolized further by conjugation with glucuronic acid.
Route of elimination Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. Fecal excretion accounts for less than 4% of the administered dose.
Half life The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity.
Clearance Not Available
Toxicity Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ranbaxy laboratories ltd
  • Novartis pharmaceuticals corp
  • Apotex inc
  • Breckenridge pharmaceutical inc
  • Cadista pharmaceuticals inc
  • Glenmark generics ltd
  • Roxane laboratories inc
  • Sun pharmaceutical industries ltd
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa
Packagers
Dosage forms
Form Route Strength
Suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
OXcarbazepine 300 mg/5ml Suspension 250ml Bottle 162.03 USD bottle
Trileptal 600 mg tablet 7.05 USD tablet
Oxcarbazepine 600 mg tablet 5.06 USD tablet
Trileptal 300 mg tablet 3.84 USD tablet
Oxcarbazepine 300 mg tablet 2.75 USD tablet
Trileptal 150 mg tablet 2.1 USD tablet
Oxcarbazepine 150 mg tablet 1.53 USD tablet
Trileptal 300 mg/5ml Suspension 0.79 USD ml
Patents
Country Patent Number Approved Expires
United States 7037525 1998-08-12 2018-08-12
Canada 2277791 2008-11-18 2018-02-12
Properties
State solid
Melting point 215.5 oC
Experimental Properties
Property Value Source
water solubility 308 mg/L at 25 oC (SRC PhysProp estimated -- MEYLAN,WM et al. (1996)) PhysProp
logP 1.5 PhysProp
Predicted Properties
Property Value Source
water solubility 1.60e-01 g/l ALOGPS
logP 1.76 ALOGPS
logP 1.82 ChemAxon Molconvert
logS -3.20 ALOGPS
pKa 15.96 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 63.40 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 71.56 ChemAxon Molconvert
polarizability 25.72 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, Bria P, Mazza S: Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav. 2007 May;10(3):397-401. Epub 2007 Feb 14. Pubmed
External Links
Resource Link
KEGG Drug D00533 Link_out
KEGG Compound C07492 Link_out
PubChem Compound 34312 Link_out
PubChem Substance 46507580 Link_out
ChemSpider 31608 Link_out
BindingDB 34179 Link_out
Therapeutic Targets Database DAP000528 Link_out
PharmGKB PA450732 Link_out
Drug Product Database 2244673 Link_out
RxList http://www.rxlist.com/cgi/generic3/oxcarbazepine.htm Link_out
Drugs.com http://www.drugs.com/cdi/oxcarbazepine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tri1563.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Oxcarbazepine Link_out
ATC Codes
  • N03AF02
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (194.9 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals. Avoid alcohol.
Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

This protein 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. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Vohora D, Saraogi P, Yazdani MA, Bhowmik M, Khanam R, Pillai KK: Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs. Drugs Today (Barc). 2010 Apr;46(4):265-77. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: inducer

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A5

Actions: inducer

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:42

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.