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targets (3) enzymes (3)
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Identification
Name Felbamate
Accession Number DB00949 (APRD00505)
Type small molecule
Groups approved
Description

Felbamate is an anticonvulsant drug used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children. It has a weak inhibitory effect on GABA receptor binding sites.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Felbamyl
  • Felbatol
  • Taloxa
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Neuroprotective Agents
  • Antiepileptic Agents
CAS number 25451-15-4
Weight Average: 238.2399
Monoisotopic: 238.095356946
Chemical Formula C11H14N2O4
InChI Key InChIKey=WKGXYQFOCVYPAC-UHFFFAOYSA-N
InChI
InChI=1S/C11H14N2O4/c12-10(14)16-6-9(7-17-11(13)15)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H2,12,14)(H2,13,15)
Plain Text
IUPAC Name
3-(carbamoyloxy)-2-phenylpropyl carbamate
SMILES
NC(=O)OCC(COC(N)=O)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Cumenes and Derivatives
Substructures
  • Carbamates and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Aromatic compounds
Pharmacology
Indication For use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.
Pharmacodynamics Felbamate is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. Receptor-binding studies in vitro indicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex. However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex.
Mechanism of action The mechanism by which felbamate exerts its anticonvulsant activity is unknown, but in animal test systems designed to detect anticonvulsant activity, felbamate has properties in common with other marketed anticonvulsants. In vitro receptor binding studies suggest that felbamate may be an antagonist at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. Antagonism of the NMDA receptor glycine binding site may block the effects of the excitatory amino acids and suppress seizure activity. Animal studies indicate that felbamate may increase the seizure threshold and may decrease seizure spread. It is also indicated that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding.
Absorption >90%
Volume of distribution
  • 756±82 mL/kg
Protein binding 20-36%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2C19 2-Phenyl-1,3-propanediol monocarbamate esterase hydrolysis 0 0
Route of elimination Not Available
Half life 20-23 hours
Clearance
  • 26 +/- 3 mL/hr/kg [single 1200 mg dose]
  • 30 +/- 8 mL/hr/kg [multiple daily doses of 3600 mg]
Toxicity LD50=5000 mg/kg (Orally in rats)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Meda pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
Felbatol 600 mg tablet 3.1 USD tablet
Felbatol 400 mg tablet 2.71 USD tablet
Felbatol 600 mg/5ml Suspension 1.43 USD ml
Patents
Country Patent Number Approved Expires
United States 4978680 1992-09-26 2009-09-26
Properties
State solid
Melting point 151.5 oC
Experimental Properties
Property Value Source
water solubility Slightly soluble in water PhysProp
logP 0.3 PhysProp
Predicted Properties
Property Value Source
water solubility 7.42e-01 g/l ALOGPS
logP 0.56 ALOGPS
logP 0.68 ChemAxon Molconvert
logS -2.51 ALOGPS
pKa 15.46 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 104.64 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 59.59 ChemAxon Molconvert
polarizability 23.52 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Leppik IE, Dreifuss FE, Pledger GW, Graves NM, Santilli N, Drury I, Tsay JY, Jacobs MP, Bertram E, Cereghino JJ, et al.: Felbamate for partial seizures: results of a controlled clinical trial. Neurology. 1991 Nov;41(11):1785-9. Pubmed
External Links
Resource Link
KEGG Drug D00536 Link_out
KEGG Compound C07501 Link_out
PubChem Compound 3331 Link_out
PubChem Substance 46506375 Link_out
ChemSpider 3214 Link_out
BindingDB 50240678 Link_out
ChEBI 4995 Link_out
ChEMBL 4995 Link_out
Therapeutic Targets Database DAP000093 Link_out
PharmGKB PA449590 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/felbamate.htm Link_out
Drugs.com http://www.drugs.com/cdi/felbamate.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Felbamate Link_out
ATC Codes
  • N03AX10
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (47.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Taking it after a meal may reduce the incidence of adverse effects.
Targets

1. Glutamate [NMDA] receptor subunit epsilon-2

Pharmacological action: yes
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: Q13224 Link_out
Gene: GRIN2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kleckner NW, Glazewski JC, Chen CC, Moscrip TD: Subtype-selective antagonism of N-methyl-D-aspartate receptors by felbamate: insights into the mechanism of action. J Pharmacol Exp Ther. 1999 May;289(2):886-94. Pubmed
  2. Harty TP, Rogawski MA: Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit. Epilepsy Res. 2000 Mar;39(1):47-55. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  4. Chang HR, Kuo CC: Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor. J Med Chem. 2008 Mar 27;51(6):1534-45. Epub 2008 Feb 27. Pubmed
  5. Luszczki JJ, Danysz W, Czuczwar SJ: Interactions of MRZ 2/576 with felbamate, lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model. Pharmacology. 2008;81(3):259-65. Epub 2008 Feb 4. Pubmed

2. Glutamate [NMDA] receptor subunit 3A

Pharmacological action: yes
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism

Organism class: human
UniProt ID: Q8TCU5 Link_out
Gene: GRIN3A 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. Glutamate [NMDA] receptor subunit epsilon-1

Pharmacological action: yes
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: Q12879 Link_out
Gene: GRIN2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. 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. 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 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. Williams DA, Foye WO, Lemke TL. Foye’s principles of medicinal chemistry. Lippincott Williams & Wilkins; 2002.
  3. 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 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 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 April 19, 2011 15:07

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.