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

Rita Judit Kiss; Ágnes Csüdör; Máté Sárosi; Zsolt András Nagy; Zsolt Gáll; Ádám Szentes; Tibor Szilágyi; Károly Orbán-Kis

doi:10.2478/amma-2024-0007

Rita Judit Kiss Physiology Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures
Ágnes Csüdör
Máté Sárosi
Zsolt András Nagy
Zsolt Gáll
Ádám Szentes
Tibor Szilágyi
Károly Orbán-Kis

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

Keywords: temporal lobe epilepsy, beta-cyclodextrin, carbamazepine, in vitro epilepsy model, seizure-like events

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 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.