Banner
Identification
Name Carbamazepine
Accession Number DB00564 (APRD00337)
Type small molecule
Groups approved
Description

An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • carbamazepine
  • Carbamezepine
Brand names
  • Apo-Carbamazepine
  • Atretol
  • Biston
  • Calepsin
  • Carbamazepen
  • Carbatrol
  • Carbazepine
  • Carbelan
  • Epitol
  • Equetro
  • Finlepsin
  • Karbamazepin
  • Lexin
  • Neurotol
  • Novo-Carbamaz
  • Nu-Carbamazepine
  • Sirtal
  • Stazepin
  • Stazepine
  • Taro-Carbamazepine
  • Taro-Carbamazepine Cr
  • Tegretal
  • Tegretol
  • Tegretol Chewtabs
  • Tegretol Cr
  • Tegretol-Xr
  • Telesmin
  • Teril
  • Timonil
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Analgesics
  • Antimanic Agents
  • Analgesics, Non-Narcotic
CAS number 298-46-4
Weight Average: 236.2686
Monoisotopic: 236.094963016
Chemical Formula C15H12N2O
InChI Key InChIKey=FFGPTBGBLSHEPO-UHFFFAOYSA-N
InChI
InChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
Plain Text
IUPAC Name
2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene-2-carboxamide
SMILES
NC(=O)N1C2=C(C=CC=C2)C=CC2=C1C=CC=C2
Plain Text
Mass Spec show (7.7 KB)
Taxonomy
Kingdom Organic
Classes
  • Dibenzazepines and Derivatives
Substructures
  • Alkanes and Alkenes
  • Dibenzazepines and Derivatives
  • Phenylpropenes
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Carbamates and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Azepines
  • Benzazepines
  • Anilines
Pharmacology
Indication For the treatment of epilepsy and pain associated with true trigeminal neuralgia.
Pharmacodynamics Carbamazepine, an anticonvulsant structurally similar to tricyclic antidepressants, is used to treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal neuralgia, and psychiatric disorders including manic-depressive illness and aggression due to dementia.
Mechanism of action Carbamazepine inhibits sustained repetitive firing by blocking use-dependent sodium channels. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus and seizure control with reduction of post-tetanic potentiation of synaptic transmission in the spinal cord. Carbamazepine also possesses anticholinergic, central antidiuretic, antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties.
Absorption Not Available
Volume of distribution Not Available
Protein binding Carbamazepine in blood is 76% bound to plasma proteins.
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 10,11-Epoxycarbamazepine 10,11-epoxidation 119 20.4
Cytochrome P450 2C8 10,11-Epoxycarbamazepine 10,11-epoxidation 757 11.98
Route of elimination Not Available
Half life 25-65 hours
Clearance Not Available
Toxicity Mild ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations. Severe intoxications may produce coma, seizures, respiratory depression, and hypotension
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Validus pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Wockhardt eu operations (swiss) ag
  • Novartis pharmaceuticals corp
  • Taro pharmaceuticals usa inc
  • Cadista pharmaceuticals inc
  • Torrent pharmaceuticals ltd
  • Teva pharmaceuticals usa inc
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Inwood laboratories inc sub forest laboratories inc
  • Pliva inc
  • Usl pharma inc
  • Warner chilcott div warner lambert co
Packagers
Dosage forms
Form Route Strength
Suspension Oral
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Equetro 300 mg capsule 2.65 USD capsule
TEGretol XR 400 mg 12 Hour tablet 2.42 USD tablet
Carbamazepine powder 2.26 USD g
Tegretol xr 400 mg tablet 2.19 USD tablet
Carbatrol 100 mg 12 Hour Capsule 2.18 USD capsule
Equetro 200 mg capsule 2.15 USD capsule
CarBAMazepine 400 mg 12 Hour tablet 2.05 USD tablet
Carbatrol 300 mg 12 Hour Capsule 1.95 USD capsule
Carbatrol 200 mg 12 Hour Capsule 1.92 USD capsule
Carbatrol er 100 mg capsule 1.84 USD capsule
Carbatrol er 200 mg capsule 1.84 USD capsule
Carbatrol er 300 mg capsule 1.84 USD capsule
Equetro 100 mg capsule 1.74 USD capsule
TEGretol XR 200 mg 12 Hour tablet 1.45 USD tablet
Tegretol xr 200 mg tablet 1.1 USD tablet
CarBAMazepine 200 mg 12 Hour tablet 1.03 USD tablet
TEGretol XR 100 mg 12 Hour tablet 0.97 USD tablet
Tegretol Cr 400 mg Sustained-Release Tablet 0.84 USD tablet
Tegretol 200 mg tablet 0.75 USD tablet
Tegretol xr 100 mg tablet 0.55 USD tablet
Tegretol Cr 200 mg Sustained-Release Tablet 0.42 USD tablet
Mylan-Carbamazepine Cr 400 mg Sustained-Release Tablet 0.4 USD tablet
Pms-Carbamazepine-Cr 400 mg Sustained-Release Tablet 0.4 USD tablet
Sandoz Carbamazepine Cr 400 mg Sustained-Release Tablet 0.4 USD tablet
Tegretol 200 mg Chewable Tablet 0.34 USD tablet
Carbamazepine 200 mg tablet 0.31 USD tablet
Epitol 200 mg tablet 0.3 USD tablet
CarBAMazepine 100 mg Chew Tabs 0.25 USD tab
Mylan-Carbamazepine Cr 200 mg Sustained-Release Tablet 0.2 USD tablet
Pms-Carbamazepine-Cr 200 mg Sustained-Release Tablet 0.2 USD tablet
Sandoz Carbamazepine Cr 200 mg Sustained-Release Tablet 0.2 USD tablet
Tegretol 100 mg Chewable Tablet 0.17 USD tablet
CarBAMazepine 100 mg/5ml Suspension 0.16 USD ml
Pms-Carbamazepine 200 mg Chewable Tablet 0.16 USD tablet
Sandoz Carbamazepine 200 mg Chewable Tablet 0.16 USD tablet
Taro-Carbamazepine 200 mg Chewable Tablet 0.16 USD tablet
Apo-Carbamazepine 200 mg Tablet 0.08 USD tablet
Novo-Carbamaz 200 mg Tablet 0.08 USD tablet
Nu-Carbamazepine 200 mg Tablet 0.08 USD tablet
Pms-Carbamazepine 100 mg Chewable Tablet 0.08 USD tablet
Sandoz Carbamazepine 100 mg Chewable Tablet 0.08 USD tablet
Taro-Carbamazepine 100 mg Chewable Tablet 0.08 USD tablet
Tegretol 20 mg/ml Suspension 0.08 USD ml
Patents
Country Patent Number Approved Expires
United States 6977253 2004-05-19 2024-05-19
United States 5284662 1994-02-08 2011-02-08
Properties
State solid
Melting point 190.2 oC
Experimental Properties
Property Value Source
water solubility 17.7 mg/L PhysProp
logP 2.3 PhysProp
Predicted Properties
Property Value Source
water solubility 1.52e-01 g/l ALOGPS
logP 2.10 ALOGPS
logP 2.77 ChemAxon Molconvert
logS -3.19 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 46.33 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 71.89 ChemAxon Molconvert
polarizability 25.00 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00252 Link_out
KEGG Compound C06868 Link_out
PubChem Compound 2554 Link_out
PubChem Substance 46507583 Link_out
ChemSpider 2457 Link_out
ChEBI 3387 Link_out
ChEMBL 3387 Link_out
Therapeutic Targets Database DAP000129 Link_out
Drug Product Database 2241882 Link_out
RxList http://www.rxlist.com/cgi/generic/carbam.htm Link_out
Drugs.com http://www.drugs.com/carbamazepine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Carbamazepine Link_out
ATC Codes
  • N03AF01
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (55.9 KB)
MSDS show (71.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid taking grapefruit or grapefruit juice throughout treatment.
  • Grapefruit can significantly increase serum levels of this product.
  • Take with food, increases availability and reduces irritation.
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. Yang YC, Huang CS, Kuo CC: Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal na+ channels. Anesthesiology. 2010 Jul;113(1):160-74. Pubmed
  4. Yang YC, Kuo CC: Inhibition of Na(+) current by imipramine and related compounds: different binding kinetics as an inactivation stabilizer and as an open channel blocker. Mol Pharmacol. 2002 Nov;62(5):1228-37. Pubmed
  5. Lipkind GM, Fozzard HA: Molecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore. Mol Pharmacol. 2010 Oct;78(4):631-8. Epub 2010 Jul 19. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, 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. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
  2. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  3. Cazali N, Tran A, Treluyer JM, Rey E, d’Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. Pubmed
  4. 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 2C8

Actions: substrate, 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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cazali N, Tran A, Treluyer JM, Rey E, d’Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. Pubmed
  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

3. Cytochrome P450 1A2

Actions: substrate, inhibitor, 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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  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

4. Cytochrome P450 2C9

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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
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

5. Cytochrome P450 2C19

Actions: inhibitor, inducer

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. 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

6. Cytochrome P450 2B6

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: P20813 Link_out
Gene: CYP2B6 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

7. 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

8. Cytochrome P450 3A7

Actions: substrate

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: P24462 Link_out
Gene: CYP3A7 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
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

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. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. Pubmed
  2. Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK: Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol. 2001 Apr;51(4):345-9. Pubmed
  3. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
  4. 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
  5. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

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.