| Identification | More | [Name]
Felbamate | [CAS]
25451-15-4 | [Synonyms]
2-PHENYL-1,3-PROPANEDIOL DICARBAMATE
2-phenylpropane-1,3-diyl dicarbamate
FELBAMATE
felbatol
1,3-Propanediol, 2-phenyl-, dicarbamate
3-propanediol,2-phenyl-dicarbamate
ADD-03055
carbamicacid,2-phenyltrimethyleneester
felbamato
Felbamyl
Taloxa
W-554
Felbanmate
FELBAMATE (2-PHENYL-1,3-PROPANEDIOL DICA
FELBAMATE 99.0%
2-PhenyltrimethyleneEster
Talox
Dicarbamic acid 2-phenyltrimethylene ester
Sch-54388 | [EINECS(EC#)]
247-001-4 | [Molecular Formula]
C11H14N2O4 | [MDL Number]
MFCD00865296 | [Molecular Weight]
238.24 | [MOL File]
25451-15-4.mol |
| Chemical Properties | Back Directory | [Appearance]
White Powder | [Melting point ]
148-1500C | [Boiling point ]
511.9±50.0 °C(Predicted) | [density ]
1.275±0.06 g/cm3(Predicted) | [Fp ]
9℃ | [storage temp. ]
Keep in dark place,Inert atmosphere,Room temperature | [solubility ]
alcohol: soluble
| [form ]
Solid | [pka]
12.99±0.50(Predicted) | [color ]
White | [Usage]
Antiepileptic, structurally similar to meprobamate | [CAS DataBase Reference]
25451-15-4(CAS DataBase Reference) | [NIST Chemistry Reference]
Felbamate(25451-15-4) |
| Hazard Information | Back Directory | [Hazard]
Low toxicity by ingestion. Human systemic
effects. | [Description]
Felbamate, characterized by its low toxicity and wide margin of safety, is efficacious in
treating refractory patients with generalized tonic-clonic and complex partial seizures as
monotherapy and adjunctive therapy.It has also been demonstrated to have a
neuroprotective effect in cerebral ischemia and hypoxia. It has been suggested that the
mechanism of its anticonvulsant activity is possibly through an interaction with the strychnineinsensitive
receptor site on the NMDA receptor complex. | [Chemical Properties]
White Powder | [Originator]
Carter-Wallace (U.S.A.) | [Uses]
Antiepileptic, structurally similar to meprobamate | [Uses]
Antiepileptic, structurally similar to meprobamate. | [Definition]
ChEBI: The bis(carbamate ester) of 2-phenylpropane-1,3-diol. An anticonvulsant, it is used in the treatment of epilepsy. | [Brand name]
Felbatol | [Biological Functions]
Felbamate (Felbatol) was introduced with the expectation
that it would become a major drug in the treatment
of epilepsy. Felbamate exhibited few manifestations of
serious toxicity in early clinical trials. Soon after its introduction,
however, it became apparent that its use was
associated with a high incidence of aplastic anemia.
Consequently, felbamate is indicated only for patients
whose epilepsy is so severe that the risk of aplastic anemia
is considered acceptable.
While its mechanism of action has not been clearly
established, felbamate shows some activity as an inhibitor
of voltage-dependent sodium channels in a manner
similar to that of phenytoin and carbamazepine.
Felbamate also interacts at the strychnine-insensitive
glycine recognition site on the NMDA receptor–
ionophore complex.Whether this effect is important to
its anticonvulsant activity is not clear. | [Biological Activity]
Anticonvulsant, acting as an antagonist at the NMDA-associated glycine binding site. | [Biochem/physiol Actions]
Anticonvulsant agent that is an allosteric antagonist at the NR2B subunit of the NMDA glutamate receptor; also has γ-aminobutyric acid (GABAA) receptor agonist properties. | [Mechanism of action]
Gabapentin is a water-soluble amino acid originally designed to be a GABA-mimetic analogue capable of penetrating the CNS.
Surprisingly, it has no direct GABA-mimetic activity, nor is it active on sodium channels. The mechanism of action remains
unknown, although it has been suggested that gabapentin may alter the metabolism or release of GABA. Gabapentin
raises brain GABA levels in patients with epilepsy. Recent studies have demonstrated gabapentin binding to calcium
channels in a manner that can be allosterically modulated.
Gabapentin is indicated as an adjunct for use against partial seizures with or without secondary generalization, in patients
older than 12 years, and as adjunct for the treatment of partial seizures in children 3 to 12 years of age. It also is approved for
the treatment of postherpetic neuralgia. | [Pharmacokinetics]
The pharmacokinetic properties for gabapentin generally are favorable, with a bioavailability of 60% when given in low doses
and somewhat less when given at higher doses because of saturable intestinal uptake by the L-amino-acid transporter.
The L-amino-acid transporter is very susceptible to substrate saturation (low Km value). Its absorption and distribution into the
CNS appears to be dependent on this amino acid transporter. Following the administration of an oral dose, gabapentin reaches
peak plasma concentration in 2 to 3 hours. Additionally, it exhibits linear pharmacokinetics. Moreover, it is not extensively
metabolized, nor is it an inducer of hepatic metabolizing enzymes. The elimination of unmetabolized gabapentin occurs by the
renal route. Although its therapeutic range is not well characterized, gabapentin has a broad therapeutic index. This implies
that a wide range of doses can be used, based on individual patient needs, without significant limitation because of
dose-dependent side effects. Protein binding is negligible. Its elimination half-life of 5 to 7 hours is not affected by the dose or
by other drugs, and its short half-life necessitates multiple daily administration. | [Clinical Use]
Felbamate is a dicarbamate that is structurally similar to the antianxiety drug meprobamate. It was approved by the U.S. FDA
for antiseizure use in 1993. Following the occurrence of rare cases of aplastic anemia and of severe hepatotoxicity associated
with the use of felbamate during early 1994, however, a black box warning was added to the drug's package insert).
Despite this, felbamate continues to be used in many patients, although not as a first-line treatment. These toxicity effects may
be attributed to the formation of toxic metabolites. Although felbamate use is now uncommon, it is used for severe
refractory seizures, either partial, myoclonic, or atonic, or in Lennox-Gastaut syndrome | [Side effects]
Adverse effects of gabapentin are uncommon and not serious. The CNS effects include mild to moderate sedation, fatigue,
ataxia, headache, dizziness, and diplopia. Gabapentin may exacerbate myoclonus, but the effect is mild and does not require
discontinuance of the drug. It has been associated with the development of neuropsychiatric adverse events in
children.
Drug interactions are infrequent with gabapentin. It does not induce hepatic metabolizing enzymes, nor do other AEDs affect its
metabolism and elimination. Antacids may decrease absorption. Gabapentin dosage may need to be decreased in patients with
renal disease or in the elderly. | [Veterinary Drugs and Treatments]
Felbamate is an anticonvulsant agent that may useful for treating
seizure disorders (especially complex partial seizures) in dogs. A
potential advantage of felbamate therapy is that when used alone
or in combination with phenobarbital and/or bromides, it does not
appear to cause additive sedation. | [Metabolism]
Although the metabolism of felbamate has not been fully characterized, felbamate is esterase hydrolyzed to its monocarbamate
metabolite, 2-phenyl-1,3-propanediol monocarbamate, which subsequently is oxidized via aldehyde dehydrogenase to its major
human metabolite 3-carbamoyl-2-phenylpropionic acid. Other metabolites include the p-hydroxy and mercapturic
acid metabolites of felbamate, which have been identified in human urine. Felbamate is a substrate for CYP2C19, with minor
activity for CYP3A4 and CYP2E1. Thompson et al. has provided evidence for the formation of the reactive metabolite,
3-carbamoyl-2-phenylpropionaldehyde (CBMA), from the alcohol oxidation of 2-phenyl-1,3-propanediol monocarbamate. CBMA
then undergoes spontaneous elimination to another reactive intermediate, 2-phenylpropenal (more commonly known as
atropaldehyde), which is proposed to play a role
in the development of toxicity during felbamate therapy. CBMA or a further product has been shown to provoke an immune
response in mice. Evidence for in vivo atropaldehyde formation was confirmed with the identification of its mercapturic acid
conjugates in human urine after felbamate administration. This is consistent with the hypothesis that atropaldehyde reacts
rapidly with thiol nucleophiles, such as glutathione, to form mercapturates. More recently, a fluorine analogue
of felbamate was synthesized in which the benzylic C2 hydrogen of the propane chain was replaced with fluorine, preventing
the formation of atropaldehyde and confirming that the acidic benzylic hydrogen plays a pivotal role in its formation. This
analogue is presently undergoing drug development. Felbamate administration exhibited linear kinetics, with a half-life of 20 to
23 hours in the absence of enzyme-inducing AEDs. Approximately 50% of an oral dose of felbamate is excreted unchanged.
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