Oxcarbazepine

Inhibition of High-Frequency Repetitive Neuronal Firing by this compound

This compound and MHD effectively inhibit high-frequency repetitive firing of neurons. patsnap.comin.govnovartis.com In vitro electrophysiological studies have demonstrated that these compounds limit sustained high-frequency repetitive firing (SRF) of sodium-dependent action potentials in cultured mouse neurons. novartis.com This effect is considered a key mechanism contributing to the blocking of seizure activity spread from an epileptic focus. novartis.com Studies in peripheral nerve fibers also indicate that this compound inhibits high-frequency firing following repetitive stimulation without affecting impulse conduction. researchgate.net

Data from in vitro studies on cultured mouse neurons illustrating the effect of this compound and MHD on sustained high frequency repetitive firing (SRF):

This table illustrates that both this compound and its active metabolite, MHD, exhibit similar potency in limiting SRF in this experimental model. novartis.com

Stabilization of Hyperexcited Neural Membranes by this compound

The blockade of voltage-gated sodium channels by this compound and MHD leads to the stabilization of hyperexcited neural membranes. fda.govin.govdrugbank.com By reducing the influx of sodium ions through these channels, the drugs make the neuronal membrane less excitable and less prone to generating abnormal electrical discharges. patsnap.com This stabilization is crucial in preventing the uncontrolled depolarization that underlies seizure initiation and propagation. drugbank.com

Diminution of Synaptic Impulse Propagation by this compound

Beyond their effects on neuronal excitability, this compound and MHD also contribute to the diminution of synaptic impulse propagation. fda.govin.govwikipedia.org By inhibiting voltage-gated sodium channels, the drugs can reduce the amplitude and frequency of action potentials reaching the presynaptic terminal. This, in turn, can lead to a decrease in the release of excitatory neurotransmitters, thereby reducing the propagation of synaptic impulses and limiting the spread of seizure activity within the brain. drugbank.comjpccr.eu

Inhibition of Glutamate Release by this compound

Glutamate is the principal excitatory neurotransmitter in the brain, and excessive glutamatergic activity is implicated in various neurological disorders, including epilepsy. Research suggests that this compound may modulate the release of neurotransmitters, including glutamate. patsnap.com

Studies using in vitro models, such as rat brain slices, have investigated the effects of this compound on glutamate release. These studies indicate that this compound can inhibit the release of endogenous glutamate elicited by stimuli that promote neuronal firing, such as the sodium channel opener veratrine. nih.govnih.gov This inhibitory effect on glutamate release is thought to be related to its ability to block sodium channels, as the influx of sodium ions is a critical step in the process of neurotransmitter release. nih.govoup.com

Despite these complexities, the modulation of excitatory neurotransmitter release, potentially through its effects on ion channels including calcium channels, is considered a contributing factor to this compound's neurobiological actions. patsnap.com

Impact of this compound on Brain-Derived Neurotrophic Factor (BDNF) Levels

Brain-Derived Neurotrophic Factor (BDNF) is a protein crucial for neuronal survival, growth, differentiation, and synaptic plasticity. nih.govfrontiersin.org It plays a vital role in maintaining neuronal health, supporting synaptic function, and facilitating learning and memory. nih.govfrontiersin.org Altered BDNF levels have been implicated in the pathophysiology of several neurological and psychiatric disorders. nih.govfrontiersin.orgresearchgate.net

Research has explored the impact of this compound on BDNF levels, particularly in conditions where BDNF dysregulation is observed, such as bipolar disorder. Studies have indicated that serum BDNF levels are often reduced in individuals with bipolar disorder. nih.govresearchgate.netnih.gov An exploratory clinical study investigated the effect of this compound monotherapy on serum BDNF levels in patients with bipolar mania. nih.govresearchgate.netnih.gov

The study found that serum BDNF levels were significantly lower in bipolar manic patients compared to healthy controls at baseline. nih.govresearchgate.netnih.gov Following four weeks of this compound monotherapy, there was a statistically significant increase in serum BDNF levels in the bipolar patient group. nih.govresearchgate.netnih.gov Although the levels did not fully normalize to those of the healthy control group within this timeframe, the observed increase suggests a favorable effect of this compound on BDNF levels. nih.gov

This finding indicates a potential neurotrophic effect of this compound, suggesting it may play a role in supporting neuronal health and plasticity by influencing BDNF levels. nih.govresearchgate.net Further research, including longer follow-up periods and larger studies, is needed to fully understand the sustained impact of this compound on BDNF and its implications for neuroprotection. nih.gov

Data Table: Change in Serum BDNF Levels

Note: Data extracted from an exploratory study on the effect of this compound on serum BDNF in bipolar mania. nih.govresearchgate.netnih.gov

Another study investigating the efficacy of levetiracetam combined with this compound in adults with temporal lobe epilepsy noted that this compound demonstrated effective suppression of excitatory postsynaptic potentials in glutamatergic synapses without negatively affecting brain-derived neurotrophic factor levels in the hippocampus. e-century.us This observation further supports the idea that this compound does not appear to have a detrimental effect on BDNF and may even contribute to its preservation or enhancement in certain brain regions. e-century.us

The relationship between the observed increase in BDNF levels and the clinical effects of this compound is an area of ongoing investigation. In the study on bipolar mania, a significant positive correlation was found between the change in Young Mania Rating Scale (YMRS) scores (indicating symptomatic improvement) and the change in serum BDNF levels, suggesting a potential link between increased BDNF and clinical response. nih.govresearchgate.netnih.gov

These findings collectively suggest that this compound's neurobiological effects may extend beyond ion channel modulation to include influencing trophic factors like BDNF, potentially contributing to neuroprotective processes.

Weak Induction of CYP3A4 by this compound

This compound and its active metabolite, MHD, are known to induce a subgroup of the CYP3A family, specifically CYP3A4 and CYP3A5 rxlist.comwikipedia.org. This induction can lead to decreased plasma concentrations of drugs that are substrates of these enzymes droracle.airxlist.com. While this compound is considered a CYP3A4 inducer, its inductive effect is generally regarded as weak compared to potent inducers like carbamazepine nih.govdroracle.aiwikipedia.orgelsevier.esthecarlatreport.com.

Research findings suggest that high doses of this compound (≥1200 mg/day) can induce CYP3A4 nih.govelsevier.esgoodrx.com. Studies evaluating CYP3A4 induction potential have shown lower fold changes in mRNA levels for this compound and MHD compared to carbamazepine pharmgkb.org. For instance, the fold change for CYP3A4 induction level was reported as 3.5 (range: 1.2-7.4) for this compound and 2.7 (range: 0.8-5.7) for 10-hydroxythis compound, while it was 8.3 (range: 3.5-14.5) for carbamazepine pharmgkb.org. Despite being a weaker inducer than carbamazepine, this effect can still be clinically significant, potentially decreasing the effectiveness of co-administered drugs metabolized by CYP3A4, such as oral contraceptives, calcium channel antagonists, and certain antipsychotics droracle.airxlist.comwikipedia.orgthecarlatreport.compsychiatrist.com.

Data on CYP3A4 induction by this compound could be presented in a table comparing the fold change in mRNA levels for this compound, MHD, and carbamazepine, based on in vitro studies.

Weak Inhibition of CYP2C19 by this compound

This compound and its active metabolite, MHD, are inhibitors of CYP2C19 nih.govdroracle.airxlist.comfda.govwikipedia.org. Inhibition of CYP2C19 can result in increased plasma concentrations of drugs that are substrates of this enzyme droracle.airxlist.comwikipedia.org. This inhibitory effect is considered clinically relevant rxlist.com.

The inhibition of CYP2C19 by this compound and MHD can lead to increased plasma levels of co-administered drugs metabolized via this pathway rxlist.comwikipedia.org. This interaction is particularly relevant for certain antiepileptic drugs and other medications that are CYP2C19 substrates wikipedia.org.

A table detailing the effect of this compound and MHD on CYP2C19 activity, potentially including in vitro inhibition constant (Ki) values if available from research, could illustrate this interaction.

Effects on Phenytoin Concentrations

This compound can increase the plasma concentrations of phenytoin nih.govwikipedia.orggoodrx.comdrugbank.comdrugs.comdrugs.com. This interaction is primarily attributed to the inhibition of CYP2C19-mediated metabolism of phenytoin by this compound and its active metabolite, MHD drugs.com. Studies have shown that phenytoin plasma levels can increase by up to 40% when this compound is administered at dosages above 1200 mg/day goodrx.comdrugs.comdrugs.com. Conversely, phenytoin, being a CYP inducer, can decrease the plasma concentrations of MHD by approximately 30% due to the induction of CYP isoenzymes goodrx.comdrugs.com. This reciprocal interaction highlights the need for close monitoring of phenytoin serum levels when co-administering with this compound, especially at higher this compound doses drugs.comdrugs.com.

An interactive table could display the observed percentage change in phenytoin plasma concentrations when co-administered with different doses of this compound, along with the effect of phenytoin on MHD levels.

Comparative Interaction Profile with Carbamazepine and Valproate

This compound is a structural derivative of carbamazepine but exhibits a different metabolic profile, leading to a lower potential for drug interactions pharmgkb.orgnih.govdroracle.ai. While carbamazepine is a potent inducer of various CYP enzymes, including CYP3A4, this compound is considered a weaker inducer of CYP3A4 and does not induce its own metabolism (autoinduction), unlike carbamazepine rxlist.comwikipedia.orgelsevier.esthecarlatreport.compharmgkb.org. This difference contributes to fewer and less pronounced pharmacokinetic interactions with this compound compared to carbamazepine droracle.aithecarlatreport.com.

Valproate (valproic acid) is primarily metabolized by glucuronidation and mitochondrial beta-oxidation, with limited involvement of the CYP system. While valproate is known to inhibit certain enzymes, its interaction profile differs from that of this compound and carbamazepine. This compound's primary metabolic pathway (reduction and glucuronidation) is generally less susceptible to induction and inhibition compared to CYP-dependent pathways, further distinguishing its interaction profile from that of carbamazepine and, to some extent, valproate nih.gov.

A comparative table summarizing the enzyme induction/inhibition profiles of this compound, carbamazepine, and valproate across key CYP enzymes (e.g., CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4) would be beneficial.

Co-administration with Levetiracetam, Gabapentin, Lamotrigine

Interactions between this compound and other commonly used AEDs like levetiracetam, gabapentin, and lamotrigine have been investigated.

Co-administration of this compound with levetiracetam may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating drugs.comdrugs.com. This appears to be related to additive central nervous system (CNS) depressant effects rather than significant pharmacokinetic interactions involving enzyme metabolism drugbank.comdrugs.comdrugs.comwikipedia.orgmims.com. Levetiracetam is primarily eliminated unchanged or undergoes enzymatic hydrolysis, with minimal CYP metabolism wikipedia.orgmims.com.

Similarly, combining this compound with gabapentin can also lead to increased CNS depressant effects like dizziness, drowsiness, and impaired coordination goodrx.comdrugbank.comdrugbank.comdrugs.com. Preclinical studies in mice have suggested a synergistic interaction between this compound and gabapentin in terms of anticonvulsant effects, without altering the brain concentrations of the co-administered drug, indicating a pharmacodynamic interaction nih.gov. Gabapentin is not significantly metabolized and is primarily excreted unchanged by the kidneys wikipedia.orgmims.com.

The interaction between this compound and lamotrigine is more complex. This compound is predicted to decrease lamotrigine concentrations, while lamotrigine is predicted to increase this compound concentrations nice.org.uk. This interaction likely involves enzyme induction by this compound affecting lamotrigine metabolism and potentially other mechanisms elsevier.esnice.org.uk. Studies have noted that this compound did not significantly alter oxidative stress parameters in mice, unlike topiramate, when co-administered with lamotrigine in a kindling model, suggesting a different interaction profile compared to some other AED combinations nih.gov.

Impact on Hormonal Contraceptive Efficacy

Coadministration of this compound with hormonal contraceptives can lead to a decrease in the plasma concentrations of the estrogen (ethinylestradiol) and progestin (levonorgestrel) components. droracle.ai This interaction is significant as it may reduce the effectiveness of hormonal contraceptives, potentially leading to unintended pregnancies. droracle.ai The reduction in efficacy is attributed to this compound's induction of CYP3A4/5 enzymes, which are involved in the metabolism of these hormones. droracle.ai

Interactions with Central Nervous System Depressants (e.g., Butriptyline, Cannabidiol)

This compound can enhance the effects of central nervous system (CNS) depressants, including substances like butriptyline and cannabidiol. drugbank.comdrugs.com Concurrent use can lead to increased side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. drugs.comdrugs.com This additive CNS depression can also impair thinking, judgment, and motor coordination, particularly in elderly individuals. drugs.com Therefore, caution is advised when this compound is used with other CNS depressants. drugs.com

Specifically regarding cannabidiol, using it with this compound may increase side effects like dizziness, drowsiness, confusion, and difficulty concentrating. drugs.com Some research in animal models suggests that this compound may increase the brain uptake of cannabidiol, and cannabidiol may inhibit the UGT enzymes that conjugate the active metabolite of this compound. rcpch.ac.uktandfonline.com

While butriptyline is mentioned as a CNS depressant that can interact with this compound, detailed specific research findings on the direct interaction between butriptyline and this compound were not extensively available in the search results. However, the general principle of additive CNS depression with such agents applies. drugbank.com

Influence on Cabazitaxel and Cabergoline Metabolism

This compound can influence the metabolism of certain medications, including cabazitaxel and cabergoline. The metabolism of both cabazitaxel and cabergoline can be increased when combined with this compound. drugbank.com This suggests that this compound, likely through its enzyme induction properties, can accelerate the breakdown of these drugs, potentially leading to decreased systemic exposure and reduced efficacy. Cabazitaxel is primarily metabolized by CYP3A4/5 and CYP2C8. wikipedia.org Cabergoline is predominantly metabolized by hydrolysis. hiv-druginteractions.org The induction of CYP3A4 by this compound droracle.ai is a likely mechanism for the increased metabolism of cabazitaxel.

Effects on Cabotegravir and Caffeine Clearance

This compound can impact the clearance of cabotegravir and caffeine. The serum concentration of cabotegravir can be decreased when it is combined with this compound. drugbank.com This interaction is significant for the effectiveness of cabotegravir, an HIV-1 integrase inhibitor. nih.gov

Regarding caffeine, this compound may increase its excretion rate. drugbank.com This increased excretion could lead to a lower serum level of caffeine, potentially resulting in a reduction in its effects. drugbank.com

Here is a summary of the interactions discussed:

Friedel-Crafts Cyclization Approaches

Friedel-Crafts cyclization is a key strategy employed in the synthesis of the dibenzo[b,f]azepine core of this compound. This reaction facilitates the intramolecular ring closure necessary to form the seven-membered ring. One approach involves the electrophilic ring closure of precursors such as 1-(2-(N-phenyl-N-tosylamino)phenyl)-2-bromoethanone, ethyl 2-(2-(N-phenyl-N-tosylamino)phenyl)acetate, or 2-(2-(N-phenyl-N-tosylamino)phenyl)acetic acid. semanticscholar.org Lewis acids like AlCl₃, often in conjunction with nitromethane (CH₃NO₂) or dichloromethane, have been effectively used to promote this cyclization. semanticscholar.org For precursors like the phenylacetate and acetic acid derivatives, P₂O₅ in toluene has also demonstrated efficacy. semanticscholar.org

Another Friedel-Crafts strategy for the large-scale synthesis of this compound starts from 1,3-dihydro-1-phenyl-2H-indol-2-one. researchgate.net This approach directly constructs the tricyclic framework. researchgate.net The success of this method is significantly influenced by the choice of the nitrogen-protecting group. researchgate.net

Industrial Processes for Key Intermediates (e.g., 10-Methoxyiminostilbene)

Industrial synthesis routes for this compound often utilize key intermediates to improve efficiency and scalability. 10-Methoxyiminostilbene (MISB) is a crucial intermediate in several such processes. acs.orgscite.aigoogle.comwipo.int

One industrial process for MISB involves starting from iminostilbene (5H-dibenzo[b,f]azepine). acs.orgresearchgate.net This route typically includes halogenation and dehalogenation steps. acs.org Subsequently, MISB is prepared by nucleophilic substitution of a vinylic bromide intermediate. acs.org While effective, this route has been associated with the use of potentially hazardous reagents and the generation of substantial effluent. acs.org

A newer industrial process for MISB utilizes N-acetyliminostilbene as a starting material. acs.org A notable feature of this process is the use of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to form a bromohydrin methyl ether intermediate. acs.org This process involves only two isolation and drying steps and generates recyclable and non-toxic byproducts like acetic acid, 5,5-dimethylhydantoin, and Et₃N·HBr, making it amenable for large-scale production. acs.orgscite.ai

Another method for preparing MISB involves using iminostilbene-5-formyl halide or a mixture thereof as a raw material. wipo.intpatsnap.com This process includes steps such as reaction with an alkali metal alcoholate solution to obtain iminostilbene-5-methyl formate, followed by reaction with dibromohydantoin in methanol, and subsequent reactions with triethylamine and alkali metal hydroxide or alcoholate to yield high-purity 10-methoxyiminostilbene. wipo.intpatsnap.com

MISB can be converted to this compound by treatment with sodium cyanate in acetic acid. acs.org An improved process for this conversion involves reacting MISB with alkali metal cyanates in the presence of an α-hydroxy acid, such as mandelic acid, to form 10-methoxycarbamazepine, which is then hydrolyzed to this compound. google.com This method has been reported to provide improved yield and quality compared to processes using mild aromatic acidic reagents like benzoic acid, which can result in lower yields. google.com

Optimization of Yield and Purity in Synthetic Pathways

Optimization of synthetic pathways is critical for achieving high yields and purity in this compound production. Various strategies have been explored to enhance these aspects.

One approach involves the careful selection of catalysts and reaction conditions. For instance, in Friedel-Crafts cyclizations, the choice of Lewis acid (e.g., AlCl₃ vs. P₂O₅) and solvent can significantly impact the yield of the desired tricyclic intermediate. semanticscholar.org

In the conversion of intermediates like 10-methoxyiminostilbene to this compound, the use of specific reagents and reaction systems has been optimized. Reacting 10-methoxyiminostilbene with cyanic acid generated in situ from an alkali metal cyanate and an α-hydroxy acid has shown improved yields compared to using mild aromatic acidic reagents. google.com

Hydrolysis conditions also play a role in purity and yield. An improved method for the hydrolysis of 10-methoxycarbamazepine to this compound involves conducting the reaction in a biphasic system where this compound is largely insoluble, while by-products and impurities are soluble in at least one phase. google.com This facilitates easier isolation and higher purity. google.com The hydrolysis is typically conducted in an organic solvent, such as a water-miscible ketone (like acetone), ether (like tetrahydrofuran), or a C₁-C₆ alcohol, at temperatures between 10°C and 40°C. google.com

Controlling reaction parameters like temperature, reaction time, and reagent ratios is crucial for maximizing yield and minimizing impurity formation. For example, in a method for preparing 10-methoxyiminostilbene, specific temperatures and reaction times are defined for steps like the reaction of iminostilbene-5-formyl halide with alkali metal alcoholate and subsequent dehydrohalogenation. google.com

Data from studies on optimizing synthesis often highlight the impact of specific conditions on yield and purity. For example, one study reported an 85% yield and 98.8% purity for this compound synthesized via a route involving a reduction and hydrolysis of a dibenzoazepine intermediate. patsnap.com Another process for preparing oximinostilbene (a precursor to this compound) reported an almost quantitative yield and very high purity by reacting an intermediate with chlorosulfonyl isocyanate at low temperatures and subsequently hydrolyzing in a suitable solvent. google.com

Table 1 provides illustrative examples of reported yields for different synthesis steps or routes.

Note: Yields can vary depending on specific conditions and scale.

Heteroannulation Reactions Utilizing the α-Enolizable Ketone

The α-enolizable ketone at the 10-position of the this compound structure is a key functional group that can participate in various reactions, particularly heteroannulation reactions. These reactions involve the formation of new heterocyclic rings by utilizing the reactivity of the enolizable ketone. mdpi.comdntb.gov.uanih.govdntb.gov.ua

Research has demonstrated that the α-enolizable ketone allows for the development of effective derivatization strategies, including [3+2], [4+2], and [4+1] heteroannulation approaches. mdpi.comdntb.gov.uanih.gov Often, these transformations require a pre-functionalization step of the this compound scaffold, although direct one-pot heterocycle construction has also been explored. mdpi.com

One strategy involves pre-functionalization at the 11-position, leading to intermediates such as α-bromo ketones. mdpi.com These α-halocarbonyl compounds are well-established precursors for the synthesis of various five- and six-membered heterocycles. mdpi.comdntb.gov.ua For example, an α-bromo ketone derivative of this compound can react with thiourea in a Hantzsch reaction to yield a thiazole derivative fused to the this compound scaffold. mdpi.com

Another approach involves pre-functionalization at the 10-position. mdpi.com For instance, the reaction of this compound with selenium dioxide can lead to the formation of a 10,11-dione derivative, which can serve as a building block for further cyclizations. mdpi.com

Development of Novel Heterocyclic Systems from this compound

The derivatization of the this compound scaffold through heteroannulation and other reactions has led to the synthesis of a structurally diverse library of novel heterocyclic systems. mdpi.comdntb.gov.uanih.gov These new compounds incorporate additional heterocyclic rings fused to the dibenzo[b,f]azepine core of this compound.

Examples of novel heterocyclic systems developed from this compound include fused thiazoles, oxazoles, and indole derivatives. mdpi.com The synthetic strategies often involve the reaction of functionalized this compound intermediates with various binucleophilic or dienophilic reagents.

For instance, a 10-(phenylhydrazono) derivative of this compound can undergo cyclization in acetic acid to form a dibenzo[2,3:6,7]azepino[4,5-b]indole-9(14H)-carboxamide. mdpi.com The reaction of a 10-(hydroxyimino) derivative with benzoyl chloride and pyridine can yield an oxazole fused system. nih.gov

These studies highlight the potential of the this compound scaffold as a versatile starting material for the creation of novel chemical structures with potential applications in medicinal chemistry and materials science. researchgate.net

Strategies for Modifying the Dibenzazepine Framework

The core structure of this compound is the dibenz[b,f]azepine ring system, specifically a 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide with a ketone at the 10-position. wikipedia.orgnih.gov Modifications to this framework are key strategies in developing derivatives with altered pharmacological profiles.

One approach involves functionalization of the dibenzo[b,f]azepine precursor. Dibenzo[b,f]azepine itself can be functionalized at various positions. beilstein-journals.org For instance, bromination of dihydrodibenzo[b,f]azepine in acetic acid can lead to tetrabrominated intermediates. beilstein-journals.org

The synthesis of this compound from 10-methoxyiminostilbene (10-methoxy-5H-dibenz[b,f]azepine) involves carbamoylation followed by hydrolysis of the methyl enol ether. beilstein-journals.orgwipo.int Another industrial process for this compound synthesis utilizes an electrophilic ring closure reaction of a benzeneacetic acid derivative in polyphosphoric acid to form the tricyclic framework. researchgate.netacs.org

Derivatization strategies can target the α-enolizable ketone at the 10-position of the dibenzazepine core in this compound. mdpi.com This allows for heteroannulation reactions, including [3+2], [4+2], and [4+1] approaches, to synthesize new heterocyclic systems fused to the this compound scaffold. mdpi.com These reactions often require pre-functionalization, although direct one-pot constructions have also been explored. mdpi.com

Pharmacological Activity of the Monohydroxy Derivative (MHD)

The monohydroxy derivative (MHD), also known as licarbazepine, is the major active metabolite of this compound. nih.govresearchgate.netnih.govnih.govtaylorandfrancis.com MHD is a chiral molecule, existing as (S)-(+)- and (R)-(-)-enantiomers. researchgate.net Both enantiomers are considered to have similar antiepileptic properties. researchgate.net

MHD exerts its anticonvulsant activity mainly by blocking voltage-gated Na+ channels, leading to the stabilization of hyperexcited neural membranes and the suppression of repetitive neuronal firing. wikipedia.orgfda.govresearchgate.net This mechanism is thought to be similar to that of carbamazepine, from which this compound is structurally derived. wikipedia.orgnih.gov While this compound is rapidly converted to MHD, the exposure to MHD is significantly higher than that of the parent drug in vivo, underscoring its role as the primary active species. fda.govnih.govtaylorandfrancis.com

MHD is primarily eliminated through glucuronidation and renal excretion. nih.govtaylorandfrancis.com A minor amount is oxidized to the pharmacologically inactive dihydroxy derivative (DHD). fda.govnih.govtaylorandfrancis.com

Development of Eslicarbazepine Acetate as a Prodrug of (S)-MHD

Eslicarbazepine acetate (ESL acetate) is a third-generation antiepileptic drug and a prodrug that is rapidly and extensively metabolized to eslicarbazepine, which is the (S)-(+)-enantiomer of MHD (S-licarbazepine). nih.govwikipedia.orgdrugbank.comnih.govpatsnap.comfda.govresearchgate.netbasicmedicalkey.comnih.govopenaccessjournals.comnih.gov This development capitalized on the pharmacological activity of the MHD metabolite.

Unlike this compound, which is metabolized to both (S)-MHD and (R)-MHD, eslicarbazepine acetate is designed to be a prodrug specifically for the (S)-enantiomer. fda.govresearchgate.netopenaccessjournals.comnih.gov This conversion occurs rapidly via hydrolytic first-pass metabolism in the liver. nih.govpatsnap.comresearchgate.net The plasma concentration of the prodrug, eslicarbazepine acetate, remains very low following administration. nih.govresearchgate.net

Eslicarbazepine (S-MHD) is the primary active moiety and is responsible for the anticonvulsant effects of eslicarbazepine acetate. nih.govdrugbank.comnih.govpatsnap.comresearchgate.net Its mechanism of action is thought to involve the inhibition of voltage-gated sodium channels, similar to MHD derived from this compound. nih.govdrugbank.compatsnap.com Studies suggest eslicarbazepine may have a selective affinity for the slow-inactivated state of sodium channels. patsnap.com

The development of eslicarbazepine acetate as a single-enantiomer prodrug represents a strategy to potentially improve the pharmacokinetic profile and tolerability compared to the racemic mixture of MHD produced from this compound. basicmedicalkey.comnih.gov Eslicarbazepine has a longer half-life than this compound and is primarily eliminated renally, largely as the unchanged form and glucuronide conjugates. nih.govwikipedia.orgpatsnap.comnih.gov

Pharmacokinetic Comparison: this compound vs. MHD vs. Eslicarbazepine

This table highlights the metabolic pathway where this compound is converted to the active MHD, and eslicarbazepine acetate is converted to the active (S)-MHD, which is eslicarbazepine.