Felbamate

Felbamate
Clinical data
Trade namesFelbatol
AHFS/Drugs.comMonograph
MedlinePlusa606011
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability>90%
MetabolismHepatic
Elimination half-life20–23 hours
Identifiers
  • (3-carbamoyloxy-2-phenylpropyl) carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.042.714 Edit this at Wikidata
Chemical and physical data
FormulaC11H14N2O4
Molar mass238.243 g·mol−1
3D model (JSmol)
  • O=C(N)OCC(c1ccccc1)COC(N)=O
  • 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) checkY
  • Key:WKGXYQFOCVYPAC-UHFFFAOYSA-N checkY
  (verify)

Felbamate sold under the brand name Felbatol, is an anticonvulsant 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. However, an increased risk of potentially fatal aplastic anemia or liver failure limit the drug's usage to severe refractory epilepsy.

Medical uses

Available forms

Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL).

Side effects

Adverse reactions include decreased appetite, vomiting, insomnia, nausea, dizziness, somnolence, and headache. Many patients report increased alertness with the drug. Two rare but very serious effects include aplastic anemia and serious liver damage. The risk of aplastic anemia is between 1:3,600 and 1:5,000, of which 30% of cases are fatal. The risk of liver damage is between 1:24,000 to 1:34,000, of which 40% of cases are fatal.

Drug interactions

Felbamate is an inhibitor of CYP2C19 – an enzyme involved in the metabolism of several commonly used medications. Felbamate interacts with several other AEDs, including phenytoin, valproate, and carbamazepine; dosage adjustments may be necessary to avoid adverse effects. Concomitant administration of felbamate and carbamazepine decreases blood levels of both drugs, while increasing the level of carbamazepine-10,11 epoxide, the active metabolite of carbamazepine.

Mechanism of action

Felbamate has been proposed to have a unique dual mechanism of action as a positive modulator of GABAA receptors and as a blocker of NMDA receptors, particularly isoforms containing the NR2B subunit. Although it is clear that felbamate does cause pharmacological inhibition of NMDA receptors, the relevance of NMDA receptor blockade as a strategy for the treatment of human epilepsy has been questioned. Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain.

History

Felbamate was discovered by Frank Berger at Wallace Laboratories.

References

  1. ↑ Rho JM, Donevan SD, Rogawski MA (March 1997). "Barbiturate-Like Actions of the Propanediol Dicarbamates Felbamate and Meprobamate". J. Pharmacol. Exp. Ther. 280 (3): 1383–91. PMID 9067327.
  2. ↑ Leppik IE, Dreifuss FE, Pledger GW, et al. (November 1991). "Felbamate for Partial Seizures: Results of a Controlled Clinical Trial". Neurology. 41 (11): 1785–9. doi:10.1212/wnl.41.11.1785. PMID 1944909. S2CID 25245002.
  3. ↑ Devinsky O, Faught RE, Wilder BJ, et al. (March 1995). "Efficacy of Felbamate Monotherapy in Patients Undergoing Presurgical Evaluation of Partial Seizures". Epilepsy Res. 20 (3): 241–6. doi:10.1016/0920-1211(94)00084-A. PMID 7796796. S2CID 21915205.
  4. ↑ Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Archived from the original on 2007-10-10. Retrieved 2008-12-25. Retrieved on December 25, 2008.
  5. ↑ Curry WJ, Kulling DL (February 1998). "Newer Antiepileptic Drugs: Gabapentin, Lamotrigine, Felbamate, Topiramate and Fosphenytoin". Am Fam Physician. 57 (3): 513–20. PMID 9475899. Archived from the original on 2011-09-27. Retrieved 2005-12-06.
  6. ↑ Rho JM, Donevan SD, Rogawski MA (Feb 1994). "Mechanism of Action of the Anticonvulsant Felbamate: Opposing Effects on N-Methyl-D-aspartate and Gamma-Aminobutyric Acid A Receptors". Annals of Neurology. 35 (2): 229–34. doi:10.1002/ana.410350216. PMID 8109904. S2CID 33913077.
  7. ↑ Kume A, Greenfield LJ, Macdonald RL, Albin RL (June 1996). "Felbamate Inhibits [3H]t-Butylbicycloorthobenzoate (TBOB) Binding and Enhances Cl– Current at the Gamma-Aminobutyric Acid A (GABAA) Receptor". J. Pharmacol. Exp. Ther. 277 (3): 1784–92. PMID 8667250.
  8. ↑ Subramaniam S, Rho JM, Penix L, Donevan SD, Fielding RP, Rogawski MA (May 1995). "Felbamate Block of the N-Methyl-D-aspartate Receptor". The Journal of Pharmacology and Experimental Therapeutics. 273 (2): 878–86. PMID 7752093.
  9. ↑ Kleckner NW, Glazewski JC, Chen CC, Moscrip TD (May 1999). "Subtype-Selective Antagonism of N-Methyl-D-aspartate Receptors by Felbamate: Insights into the Mechanism of Action". The Journal of Pharmacology and Experimental Therapeutics. 289 (2): 886–894. PMID 10215667.
  10. ↑ Harty TP, Rogawski MA (March 2000). "Felbamate Block of Recombinant N-Methyl-D-aspartate Receptors: Selectivity for the NR2B Subunit". Epilepsy Research. 39 (1): 47–55. doi:10.1016/s0920-1211(99)00108-4. PMID 10690753. S2CID 25467576.
  11. ↑ Chang HR, Chung-Chin Kuo CC (March 2008). "Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor". Journal of Medicinal Chemistry. 51 (6): 1534–45. doi:10.1021/jm0706618. PMID 18311896.
  12. ↑ Rogawski MA (March 2011). "Revisiting AMPA Receptors as an Antiepileptic Drug Target". Epilepsy Currents. 11 (2): 56–63. doi:10.5698/1535-7511-11.2.56. PMC 3117497. PMID 21686307.
  13. ↑ "Frank Berger". Daily Telegraph. 2008-04-07. ISSN 0307-1235. Retrieved 2018-09-22.