<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective</bold>: Pharmacoresistant epilepsy represents a significant global health challenge, necessitating novel therapeutic approaches. Despite advances in antiseizure medications, many patients remain treatment-resistant partially due to complex pharmacokinetic issues. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers potential solutions by forming inclusion complexes, thereby improving anti-seizure medication’s efficacy. This study aimed to investigate the effect of beta-cyclodextrin and beta-cyclodextrin-complexed carbamazepine on epileptiform activities, using an in vitro model of temporal lobe epilepsy.
<bold>Methods</bold>: Seizure-like neuronal activity was induced using the low-magnesium model. Local field potentials were recorded from transverse rat hippocampal slices immersed in epileptogenic artificial cerebrospinal fluid, followed by the administration of either beta-cyclodextrin or carbamazepine, the latter in 100 micromolar concentration.
<bold>Results</bold>: Beta cyclodextrin, applied alone, significantly reduced the duration of interictal and ictal phases while increasing the frequency of seizure-like events. Carbamazepine exhibited an important anticonvulsant effect, significantly reducing ictal and postictal phase durations. However, the frequency of seizure-like events was increased. Notably, in some of the slices, carbamazepine completely suppressed epileptiform activity.
<bold>Conclusions</bold>: Beta cyclodextrin had an effect on its own; it shortened seizure durations and increased their frequency. Carbamazepine in complexed form, as used in our study, exhibited anticonvulsant efficacy, emphasizing the feasibility of solubility enhancement by this method. This study provides insights into potential therapeutic strategies for pharmacoresistant temporal lobe epilepsy, improving the pharmacological properties of the drugs. As cyclodextrins emerge as promising excipients for antiepileptic drugs with poor solubility, more effort is needed in order to elucidate the underlying mechanisms of their effects.
</abstract>

Objective: Pharmacoresistant epilepsy represents a significant global health challenge, necessitating novel therapeutic approaches. Despite advances in antiseizure medications, many patients remain treatment-resistant partially due to complex pharmacokinetic issues. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers potential solutions by forming inclusion complexes, thereby improving anti-seizure medication’s efficacy. This study aimed to investigate the effect of beta-cyclodextrin and beta-cyclodextrin-complexed carbamazepine on epileptiform activities, using an in vitro model of temporal lobe epilepsy.
Methods: Seizure-like neuronal activity was induced using the low-magnesium model. Local field potentials were recorded from transverse rat hippocampal slices immersed in epileptogenic artificial cerebrospinal fluid, followed by the administration of either beta-cyclodextrin or carbamazepine, the latter in 100 micromolar concentration.
Results: Beta cyclodextrin, applied alone, significantly reduced the duration of interictal and ictal phases while increasing the frequency of seizure-like events. Carbamazepine exhibited an important anticonvulsant effect, significantly reducing ictal and postictal phase durations. However, the frequency of seizure-like events was increased. Notably, in some of the slices, carbamazepine completely suppressed epileptiform activity.
Conclusions: Beta cyclodextrin had an effect on its own; it shortened seizure durations and increased their frequency. Carbamazepine in complexed form, as used in our study, exhibited anticonvulsant efficacy, emphasizing the feasibility of solubility enhancement by this method. This study provides insights into potential therapeutic strategies for pharmacoresistant temporal lobe epilepsy, improving the pharmacological properties of the drugs. As cyclodextrins emerge as promising excipients for antiepileptic drugs with poor solubility, more effort is needed in order to elucidate the underlying mechanisms of their effects.

Effect of carbamazepine-beta-cyclodextrin inclusion complex on seizure-like events in an in vitro model of temporal lobe epilepsy

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures

Pharmacology and Clinical Pharmacy Department

Acta Marisiensis - Seria Medica

This work is licensed under the Creative Commons Attribution 4.0 International License.

Objective: Pharmacoresistant epilepsy represents a significant global health challenge, necessitating novel therapeutic approaches. Despite advances in...

Effect of carbamazepine-beta-cyclodextrin inclusion complex on seizure-like events in an in vitro model of temporal lobe epilepsy

Publicado en línea: 03 jul 2024

Páginas: 50 - 57

Recibido: 20 mar 2024

Aceptado: 11 abr 2024

DOI: https://doi.org/10.2478/amma-2024-0007

Palabras clave
temporal lobe epilepsy, beta-cyclodextrin, carbamazepine, in vitro epilepsy model, seizure-like events

© 2024 Rita-Judit Kiss et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Effect of carbamazepine-beta-cyclodextrin inclusion complex on seizure-like events in an in vitro model of temporal lobe epilepsy

Publicado en línea: 03 jul 2024

Páginas: 50 - 57

Recibido: 20 mar 2024

Aceptado: 11 abr 2024

DOI: https://doi.org/10.2478/amma-2024-0007

Palabras clavetemporal lobe epilepsy, beta-cyclodextrin, carbamazepine, in vitro epilepsy model, seizure-like events

© 2024 Rita-Judit Kiss et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Palabras clave
temporal lobe epilepsy, beta-cyclodextrin, carbamazepine, in vitro epilepsy model, seizure-like events