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Advances in Antiepileptic Drugs

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 4327

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Dr. Barbara Miziak

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Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland
Interests: epilepsy; epileptogenesis; status epilepticus; neuroprotection; antiepileptic drugs; seizures

Special Issue Information

Dear Colleagues,

Today, pharmacotherapy is a major aspect of the therapeutic management of patients with most conditions. In almost every disease entity, pharmaceuticals can be used either as monotherapy or as polytherapy, depending on the need. The situation is similar for antiepileptic drugs (AEDs). AEDs have been known since 1938, when phenytoin was introduced. Today, there are three generations of AEDs, of which the third generation is defined as those introduced after 2000. AEDs have diverse mechanisms of action, the most commonly cited being potentiation of GABA, blockade of voltage-dependent sodium or calcium channels, or inhibition of glutamate-induced excitation. Newer AEDs also have more favorable pharmacokinetics and a much lower incidence of side effects. The choice of AED as well as its dose is adapted not only to the type of seizure but also to the medical characteristics of the patient. If AED polytherapy is required, adverse pharmacokinetic as well as pharmacodynamic interactions should be avoided. In addition to the treatment of epilepsy (including severe epileptic syndromes such as Dravet syndrome or Lennox Gastaut), AEDs are also used in the treatment of psychiatric disorders (e.g., bipolar disorder), neurological disorders (e.g., neuropathic pain, migraine), as well as in some neurosurgical patients. Despite enormous progress in medical and pharmaceutical science, there is still a need to find safer and more effective therapies.

Dr. Barbara Miziak
Guest Editor

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Published Papers (4 papers)

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Research

15 pages, 4067 KiB

Open AccessArticle

Assessing the Effectiveness of Eslicarbazepine Acetate in Reducing Audiogenic Reflex Seizures in the GASH/Sal Model of Epilepsy

by Jaime Gonçalves-Sánchez, Thomas Ramírez-Santos, Dolores E. López, Jesús M. Gonçalves-Estella and Consuelo Sancho

Biomedicines 2024, 12(5), 1121; https://doi.org/10.3390/biomedicines12051121 - 18 May 2024

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Abstract

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug indicated as monotherapy for adults with newly diagnosed epilepsy and as adjunctive therapy for the treatment of partial seizures. Our aim was to assess the effectiveness and safety of both acute and repeated ESL administration against reflex audiogenic seizures, as shown by the Genetic Audiogenic Seizures Hamster from Salamanca (GASH/Sal). Animals were subject to the intraperitoneal administration of ESL, applying doses of 100, 150 and 200 mg/kg for the acute study, whereas a daily dose of 100 mg/kg was selected for the subchronic study, which lasted 14 days. In both studies, the anticonvulsant effect of the therapy was evaluated using neuroethological methods. To assess the safety of the treatment, behavioral tests were performed, hematological and biochemical liver profiles were obtained, and body weight was monitored. In addition, the ESL levels in blood were measured after the acute administration of a 200 mg/kg dose. Treatment with ESL caused a reduction in seizure severity. No statistically significant differences were detected between the selected doses or between the acute or repeated administration of the drug. To summarize, the intraperitoneal administration of ESL is safe and shows an anticonvulsant effect in the GASH/Sal. Full article

(This article belongs to the Special Issue Advances in Antiepileptic Drugs)

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17 pages, 7800 KiB

Open AccessArticle

Additive Anticonvulsant Profile and Molecular Docking Analysis of 5,5′-Diphenylhydantoin Schiff Bases and Phenytoin

by Jana Tchekalarova, Petar Todorov, Miroslav Rangelov, Tsveta Stoyanova and Nadezhda Todorova

Biomedicines 2023, 11(11), 2912; https://doi.org/10.3390/biomedicines11112912 - 27 Oct 2023

Cited by 2 | Viewed by 997

Abstract

Four 5,5′-diphenylhydantoin Schiff bases possessing different aromatic species (SB1–SB4) were recently synthesized and characterized using spectroscopic and electrochemical tools. The present study aimed to ascertain the anticonvulsant activity of the novel phenytoin derivatives SB1-Ph, SB2-Ph, SB3-Ph, and SB4-Ph, containing different electron-donor and electron-acceptor groups, and their possible mechanism of action. The SB2-Ph exhibited the highest potency to suppress the seizure spread with ED₅₀ = 8.29 mg/kg, comparable to phenytoin (ED₅₀ = 5.96 mg/kg). While SB2-Ph did not produce neurotoxicity and sedation, it decreased locomotion and stereotypy compared to control. When administered in combination, the four Schiff bases decreased the phenytoin ED₅₀ by more than 2× and raised the protective index by more than 7× (phenytoin+SB2-Ph). The strongest correlation between in-vivo and docking study results was found for ligands’ interaction energies with kappa and delta receptors. These data, combined with the worst interaction energies of our ligands with the mu receptor, suggest that the primary mechanism of their action involves the kappa and delta receptors, where the selectivity to the kappa receptor leads to higher biological effects. Our findings suggest that the four Schiff bases might be promising candidates with potential applications as a safe and effective adjuvant in epilepsy. Full article

(This article belongs to the Special Issue Advances in Antiepileptic Drugs)

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14 pages, 645 KiB

Open AccessArticle

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients

by Rania Magadmi, Reem Alyoubi, Tahani Moshrif, Duaa Bakhshwin, Bandar A. Suliman, Fatemah Kamel, Maha Jamal, Abdulhadi S. Burzangi and Sulman Basit

Biomedicines 2023, 11(9), 2505; https://doi.org/10.3390/biomedicines11092505 - 11 Sep 2023

Cited by 2 | Viewed by 981

Abstract

Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 (ABCB1) gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of ABCB1 rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the ABCB1 gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients. Full article

(This article belongs to the Special Issue Advances in Antiepileptic Drugs)

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16 pages, 159978 KiB

Open AccessArticle

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities

by Barakat M. Alrashdi, Alaa Fehaid, Rami B. Kassab, Sara Rizk, Ola A. Habotta and Ahmed E. Abdel Moneim

Biomedicines 2023, 11(7), 1955; https://doi.org/10.3390/biomedicines11071955 - 11 Jul 2023

Cited by 1 | Viewed by 1403

Abstract

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na₂SeO₃) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect. Full article

(This article belongs to the Special Issue Advances in Antiepileptic Drugs)

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