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Biomedicines
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Advances in Antiepileptic Drugs
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Advances in Antiepileptic Drugs

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 3729

Special Issue Editor

Dr. Barbara Miziak

E-Mail Website
Guest Editor
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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

17 pages, 7800 KiB  
Article
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 944
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, [...] Read more.
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  
Article
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 928
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 [...] Read more.
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  
Article
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 1355
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, [...] Read more.
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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