Felbamate

Identification

Summary

Felbamate is an anticonvulsant used to treat severe epilepsy.

Brand Names
Felbatol
Generic Name
Felbamate
DrugBank Accession Number
DB00949
Background

Felbamate is an anticonvulsant drug used in the treatment of epilepsy. In particular, in the adult patient population, it can be employed to treat partial seizures (with and without generalization). Alternatively, it is used to treat partial and generalized seizures associated with Lennox-Gastaut syndrome in children. It has a weak inhibitory effect on GABA receptor binding sites.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 238.2399
Monoisotopic: 238.095356946
Chemical Formula
C11H14N2O4
Synonyms
  • 2-phenyl-1,3-propanediol dicarbamate
  • carbamic acid 2-phenyltrimethylene ester
  • Carbamic acid 3-carbamoyloxy-2-phenyl-propyl ester
  • Felbamate
  • Felbamato
  • Felbamatum
External IDs
  • ADD-03055
  • W-554

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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AGlutamate receptor ionotropic, NMDA 2B
antagonist
Humans
AGlutamate receptor ionotropic, NMDA 2A
antagonist
Humans
Absorption

>90%

Volume of distribution
  • 756±82 mL/kg
Protein binding

20-36%

Metabolism

Hepatic

Hover over products below to view reaction partners

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]
Adverse Effects
Adverseeffects
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Toxicity

LD50=5000 mg/kg (Orally in rats)

Pathways
PathwayCategory
Felbamate Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Felbamate is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Felbamate can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Felbamate can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Felbamate.
AbirateroneThe metabolism of Felbamate can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Felbamate.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Felbamate.
AcetaminophenFelbamate may increase the hepatotoxic activities of Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Felbamate.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Felbamate.
Interactions
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Food Interactions
  • Avoid alcohol.

Products

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International/Other Brands
Felbamyl / Taloxa
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FelbatolTablet400 mg/1OralMEDA Pharmaceuticals1993-07-29Not applicableUS flag
FelbatolSuspension600 mg/5mLOralMEDA Pharmaceuticals1993-07-29Not applicableUS flag
FelbatolTablet600 mg/1OralMEDA Pharmaceuticals1993-07-29Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FelbamateTablet400 mg/1OralCadila Healthcare Limited2017-08-15Not applicableUS flag
FelbamateTablet400 mg/1OralCorePharma, LLC2017-03-062019-01-31US flag
FelbamateTablet400 mg/1OralMarlex Pharmaceuticals Inc2015-08-01Not applicableUS flag
FelbamateSuspension600 mg/5mLOralVistapharm, Inc.2019-06-24Not applicableUS flag
FelbamateTablet400 mg/1Oralbryant ranch prepack2018-09-04Not applicableUS flag
FelbamateSuspension600 mg/5mLOralWallace Pharmaceuticals Inc.2011-11-23Not applicableUS flag
FelbamateSuspension600 mg/5mLOralNorth Star Rx Llc2018-04-10Not applicableUS flag
FelbamateTablet400 mg/1OralViona Pharmaceuticals Inc2020-03-03Not applicableUS flag
FelbamateTablet400 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2017-04-20Not applicableUS flag
FelbamateSuspension600 mg/5mLOralAmneal Pharmaceuticals LLC2011-12-16Not applicableUS flag

Categories

ATC Codes
N03AX10 — Felbamate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Carbamate esters / Organic carbonic acids and derivatives / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aromatic homomonocyclic compound / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carbamate ester (CHEBI:4995)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
X72RBB02N8
CAS number
25451-15-4
InChI Key
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

References

General References
  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. [Article]
Human Metabolome Database
HMDB0015084
KEGG Drug
D00536
KEGG Compound
C07501
PubChem Compound
3331
PubChem Substance
46506375
ChemSpider
3214
BindingDB
50088430
RxNav
24812
ChEBI
4995
ChEMBL
CHEMBL1094
ZINC
ZINC000001530803
Therapeutic Targets Database
DAP000093
PharmGKB
PA449590
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Felbamate
MSDS
Download (47.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableEpilepsies1
Not AvailableRecruitingNot AvailableEpilepsies1

Pharmacoeconomics

Manufacturers
  • Meda pharmaceuticals inc
Packagers
  • Aptuit Laurus Pvt Ltd.
  • Atlantic Biologicals Corporation
  • Kaiser Foundation Hospital
  • Meda AB
Dosage Forms
FormRouteStrength
SuspensionOral600 mg/5mL
TabletOral400 mg/1
TabletOral600 mg/1
SuspensionOral120 mg/ml
TabletOral400 MG
TabletOral600 MG
TabletOral
SuspensionOral
Prices
Unit descriptionCostUnit
Felbatol 600 mg tablet3.1USD tablet
Felbatol 400 mg tablet2.71USD tablet
Felbatol 600 mg/5ml Suspension1.43USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4978680No1990-12-182009-09-26US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)151.5 °CPhysProp
water solubilitySlightly soluble in waterNot Available
logP0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.742 mg/mLALOGPS
logP0.56ALOGPS
logP0.68ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)14.98ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area104.64 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity59.59 m3·mol-1ChemAxon
Polarizability23.52 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9544
Blood Brain Barrier+0.9805
Caco-2 permeable-0.6324
P-glycoprotein substrateNon-substrate0.783
P-glycoprotein inhibitor INon-inhibitor0.9551
P-glycoprotein inhibitor IINon-inhibitor0.932
Renal organic cation transporterNon-inhibitor0.9039
CYP450 2C9 substrateNon-substrate0.9009
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7942
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9184
CYP450 2D6 inhibitorInhibitor0.7126
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9271
Ames testNon AMES toxic0.7602
CarcinogenicityNon-carcinogens0.8338
BiodegradationNot ready biodegradable0.8068
Rat acute toxicity1.7095 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9872
hERG inhibition (predictor II)Non-inhibitor0.9786
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0udi-5900000000-673caaab3dded596924c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-2900000000-880b1fb1822a512a352c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-016r-1900000000-f04127a0f39b9e0b001f

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic site...
Gene Name
GRIN2B
Uniprot ID
Q13224
Uniprot Name
Glutamate receptor ionotropic, NMDA 2B
Molecular Weight
166365.885 Da
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. [Article]
  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. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. doi: 10.1021/jm0706618. Epub 2008 Feb 27. [Article]
  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. doi: 10.1159/000114870. Epub 2008 Feb 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of sub...
Gene Name
GRIN2A
Uniprot ID
Q12879
Uniprot Name
Glutamate receptor ionotropic, NMDA 2A
Molecular Weight
165281.215 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Johannessen SI, Landmark CJ: Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254. [Article]
  2. Glue P, Banfield CR, Perhach JL, Mather GG, Racha JK, Levy RH: Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation. Clin Pharmacokinet. 1997 Sep;33(3):214-24. doi: 10.2165/00003088-199733030-00004. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. [Article]
  2. Turnheim K: [Drug interactions with antiepileptic agents]. Wien Klin Wochenschr. 2004 Feb 28;116(4):112-8. [Article]
  3. Foye, William O.;Williams, David A.;Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry (5th ed.). Lippincott Williams & Wilkins. [ISBN:0683307371]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Glue P, Banfield CR, Perhach JL, Mather GG, Racha JK, Levy RH: Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation. Clin Pharmacokinet. 1997 Sep;33(3):214-24. doi: 10.2165/00003088-199733030-00004. [Article]
  2. Pietrzak B, Czarnecka E: Influence of felbamate on selected central effects of ethanol in experimental animals. Acta Pol Pharm. 2004 May-Jun;61(3):209-13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Glue P, Banfield CR, Perhach JL, Mather GG, Racha JK, Levy RH: Pharmacokinetic interactions with felbamate. In vitro-in vivo correlation. Clin Pharmacokinet. 1997 Sep;33(3):214-24. doi: 10.2165/00003088-199733030-00004. [Article]
  2. Drug Interactions & Labeling - FDA [Link]
  3. UMN Interaction Table, CYP450 [Link]

Drug created on June 13, 2005 13:24 / Updated on May 07, 2021 21:18