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Identification
NameFelbamate
Accession NumberDB00949  (APRD00505)
Typesmall molecule
Groupsapproved
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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
FelbamylNot Available
FelbatolNot Available
TaloxaNot Available
Brand mixturesNot Available
Categories
CAS number25451-15-4
WeightAverage: 238.2399
Monoisotopic: 238.095356946
Chemical FormulaC11H14N2O4
InChI KeyWKGXYQFOCVYPAC-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)
IUPAC Name
3-(carbamoyloxy)-2-phenylpropyl carbamate
SMILES
NC(=O)OCC(COC(N)=O)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassNot Available
Direct parentBenzene and Substituted Derivatives
Alternative parentsCarbamic Acids and Derivatives; Ethers; Polyamines
Substituentscarbamic acid derivative; polyamine; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzene and substituted derivatives. These are aromatic compounds containing at least one benzene ring.
Pharmacology
IndicationFor 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.
PharmacodynamicsFelbamate 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 actionThe 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 binding20-36%
Metabolism

Hepatic

SubstrateEnzymesProduct
Felbamate
2-Phenyl-1,3-propanediol monocarbamateDetails
Felbamate
p-HydroxyfelbamateDetails
Felbamate
2-HydroxyfelbamateDetails
2-Phenyl-1,3-propanediol monocarbamate
3-Carbamoyl-2-phenylpropionaldehydeDetails
3-Carbamoyl-2-phenylpropionaldehyde
Not Available
AtropaldehydeDetails
3-Carbamoyl-2-phenylpropionaldehyde
Not Available
4-Hydroxy-5-phenyltetrahydro-1,3-oxazin-2-oneDetails
3-Carbamoyl-2-phenylpropionaldehyde
3-Carbamoyl-2-phenylpropionic acidDetails
4-Hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one
5-Phenyl-1,3-oxazinane-2,4-dioneDetails
5-Phenyl-1,3-oxazinane-2,4-dione
Not Available
3-Carbamoyl-2-phenylpropionic acidDetails
Route of eliminationNot Available
Half life20-23 hours
Clearance
  • 26 +/- 3 mL/hr/kg [single 1200 mg dose]
  • 30 +/- 8 mL/hr/kg [multiple daily doses of 3600 mg]
ToxicityLD50=5000 mg/kg (Orally in rats)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Felbamate Metabolism PathwayDrug metabolismSMP00633
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9544
Blood Brain Barrier + 0.9805
Caco-2 permeable - 0.6324
P-glycoprotein substrate Non-substrate 0.783
P-glycoprotein inhibitor I Non-inhibitor 0.9551
P-glycoprotein inhibitor II Non-inhibitor 0.932
Renal organic cation transporter Non-inhibitor 0.9039
CYP450 2C9 substrate Non-substrate 0.9009
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7942
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9184
CYP450 2D6 substrate Inhibitor 0.7126
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9271
Ames test Non AMES toxic 0.7602
Carcinogenicity Non-carcinogens 0.8338
Biodegradation Not ready biodegradable 0.8068
Rat acute toxicity 1.7095 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9872
hERG inhibition (predictor II) Non-inhibitor 0.9786
Pharmacoeconomics
Manufacturers
  • Meda pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
SuspensionOral
TabletOral
Prices
Unit descriptionCostUnit
Felbatol 600 mg tablet3.1USDtablet
Felbatol 400 mg tablet2.71USDtablet
Felbatol 600 mg/5ml Suspension1.43USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States49786801992-09-262009-09-26
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point151.5 °CPhysProp
water solubilitySlightly soluble in waterNot Available
logP0.3Not Available
Predicted Properties
PropertyValueSource
water solubility7.42e-01 g/lALOGPS
logP0.56ALOGPS
logP0.68ChemAxon
logS-2.5ALOGPS
pKa (strongest acidic)14.98ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count2ChemAxon
polar surface area104.64ChemAxon
rotatable bond count7ChemAxon
refractivity59.59ChemAxon
polarizability23.52ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG DrugD00536
KEGG CompoundC07501
PubChem Compound3331
PubChem Substance46506375
ChemSpider3214
BindingDB50240678
ChEBI4995
ChEMBLCHEMBL1094
Therapeutic Targets DatabaseDAP000093
PharmGKBPA449590
RxListhttp://www.rxlist.com/cgi/generic3/felbamate.htm
Drugs.comhttp://www.drugs.com/cdi/felbamate.html
WikipediaFelbamate
ATC CodesN03AX10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(47.1 KB)
Interactions
Drug Interactions
Drug
CarbamazepineDecreased effect of both products
EthotoinIncreased phenytoin levels and decreased felbamate levels
FosphenytoinIncreased phenytoin levels and decreased felbamate levels
MephenytoinIncreased phenytoin levels and decreased felbamate levels
PhenobarbitalFelbamate increases the effect and toxicity of phenobarbital/primidone
PhenytoinIncreased phenytoin levels and decreased felbamate levels
PrimidoneFelbamate may increase the effect and toxicity of primidone.
QuinupristinThis combination presents an increased risk of toxicity
TelithromycinTelithromycin may reduce clearance of Felbamate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Felbamate if Telithromycin is initiated, discontinued or dose changed.
TriprolidineThe CNS depressants, Triprolidine and Felbamate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
UlipristalConcomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
Valproic AcidFelbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of felbamate by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of felbamate if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Taking it after a meal may reduce the incidence of adverse effects.

Targets

1. Glutamate receptor ionotropic, NMDA 2B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 2B Q13224 Details

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 receptor ionotropic, NMDA 3A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details

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 receptor ionotropic, NMDA 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 2A Q12879 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12