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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
CategoriesNot Available
CAS number25451-15-4
WeightAverage: 238.2399
Monoisotopic: 238.095356946
Chemical FormulaC11H14N2O4
InChI KeyInChIKey=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)
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
    AtropaldehydeDetails
    3-Carbamoyl-2-phenylpropionaldehyde
      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
        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.

        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

        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

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