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
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FelbatolTablet400 mg/1OralMeda Pharmaceuticals Ltd1993-07-29Not applicableUs
FelbatolSuspension600 mg/5mLOralMeda Pharmaceuticals Ltd1993-07-29Not applicableUs
FelbatolTablet600 mg/1OralMeda Pharmaceuticals Ltd1993-07-29Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FelbamateTablet600 mg/1OralAmneal Pharmaceuticals2011-09-16Not applicableUs
FelbamateSuspension600 mg/5mLOralNorth Star Rx Llc2018-04-10Not applicableUs
FelbamateTablet600 mg/1OralCorePharma, LLC2017-03-062019-04-30Us
FelbamateTablet400 mg/1OralMarlex Pharmaceuticals Inc2015-08-01Not applicableUs
FelbamateSuspension600 mg/5mLOralWallace Pharmaceuticals Inc.2011-11-23Not applicableUs
FelbamateTablet600 mg/1OralANI Pharmaceuticals, Inc.2018-09-04Not applicableUs
FelbamateTablet600 mg/1OralAlvogen Inc.2016-12-28Not applicableUs
FelbamateTablet400 mg/1OralMylan Pharmaceuticals2016-01-122018-03-31Us
FelbamateTablet400 mg/1OralCadila Pharnmaceuticals2017-08-15Not applicableUs
FelbamateTablet400 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2017-04-20Not applicableUs
International/Other Brands
Felbamyl / Taloxa
Categories
UNII
X72RBB02N8
CAS number
25451-15-4
Weight
Average: 238.2399
Monoisotopic: 238.095356946
Chemical Formula
C11H14N2O4
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

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.

Associated Conditions
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
Human
AGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
AGlutamate receptor ionotropic, NMDA 2A
antagonist
Human
Absorption

>90%

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

20-36%

Metabolism

Hepatic

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
PathwayCategory
Felbamate Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Felbamate.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Felbamate.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Felbamate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineFelbamate may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Felbamate is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Felbamate.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Felbamate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Felbamate.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Felbamate is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Felbamate.
Food Interactions
  • Taking it after a meal may reduce the incidence of adverse effects.

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. [PubMed:1944909]
External Links
Human Metabolome Database
HMDB0015084
KEGG Drug
D00536
KEGG Compound
C07501
PubChem Compound
3331
PubChem Substance
46506375
ChemSpider
3214
BindingDB
50088430
ChEBI
4995
ChEMBL
CHEMBL1094
Therapeutic Targets Database
DAP000093
PharmGKB
PA449590
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Felbamate
ATC Codes
N03AX10 — Felbamate
MSDS
Download (47.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBipolar Disorder (BD)1

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
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)
US4978680No1990-12-182009-09-26Us

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

Taxonomy

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
Monocyclic benzene moiety / Carbamic acid ester / Carbonic acid derivative / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Organonitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carbamate ester (CHEBI:4995)

Targets

Kind
Protein
Organism
Human
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. [PubMed:10215667]
  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:10690753]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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. [PubMed:18311896]
  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. [PubMed:18253065]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein phosphatase 2a binding
Specific Function
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 ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
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. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Johannessen SI, Landmark CJ: Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254. [PubMed:21358975]
Kind
Protein
Organism
Human
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. [PubMed:8806399]
  3. Turnheim K: [Drug interactions with antiepileptic agents]. Wien Klin Wochenschr. 2004 Feb 28;116(4):112-8. [PubMed:15038401]
  4. Foye, William O.;Williams, David A.;Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry (5th ed.). Lippincott Williams & Wilkins. [ISBN:0683307371]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. [PubMed:9314612]
  2. Drug Interactions & Labeling - FDA [Link]
  3. UMN Interaction Table, CYP450 [Link]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 21:57