Metabolomics-Based Study on the Anticonvulsant Mechanism of Acorus tatarinowii: GABA Transaminase Inhibition Alleviates PTZ-Induced Epilepsy in Rats

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 175 - 175

Published: March 4, 2025

Background/Objectives: Epilepsy is a common chronic and recurrent neurological disorder that poses threat to human health, Acorus tatarinowii Schott (ATS), traditional Chinese medicine, used treat it. This study aimed determine its effects on plasma metabolites. Moreover, the possible mechanism of intervention in epilepsy was preliminarily explored, combined with network pharmacology. Methods: An epileptic model rats established using pentylenetetrazol. The potential targets pathways ATS were predicted by Ultra Performance Liquid Chromatography–Quadrupole–Time Flight Mass Spectrometrynce Spectrometryance Spectrometry statistical analyses profile metabolites identify ATS’s epilepsy. Results: Kyoto Encyclopedia Genes Genomes enrichment analysis revealed involved regulating multiple signaling pathways, mainly including neuroactive ligand–receptor interaction GABAerGamma-aminobutyrate transaminaseAminobutyrate Transaminaseapse pathway. treatment restored 19 epiGamma-aminobutyrate transaminaseminobutyrate Transaminase rats, affecting lysine, histidine, purine metabolism. GABA-T found as new key target for treating ATS. IC50 inhibiting activity 57.9 μg/mL. Through metabolomic analysis, we detected changes levels certain related GABAergic system. These metabolite can be correlated One limitations this correlation between altered seizure severity remains unfinished, which restricts more in-depth exploration underlying biological mechanisms. In future, our research will focus conducting severity. Conclusions: results improved understanding treatment, potentially leading better therapies. identification their associated offers novel therapeutic By modulating these metabolites, future therapies could designed manage disorder. insights from pharmacology guide development effective antiepileptic drugs, paving way clinical outcomes patients.

Language: Английский

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Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 24, 2024

Epilepsy is one of the most common, severe, chronic, potentially life-shortening neurological disorders, characterized by a persisting predisposition to generate seizures. It affects more than 60 million individuals globally, which major burdens in seizure-related mortality, comorbidities, disabilities, and cost. Different treatment options have been used for management epilepsy. More 30 drugs approved US FDA against However, one-quarter epileptic still show resistance current medications. About 90% low middle-income countries do not access medication. In these countries, plant extracts treat various diseases, including These medicinal plants high therapeutic value contain valuable phytochemicals with diverse biomedical applications. multifactorial disease, therefore, multitarget approaches such as or extracted are needed, can target multiple pathways. Numerous shown epilepsy animal models targeting receptors, enzymes, metabolic could be humans future; however, further research needed study exact mechanism action, toxicity, dosage reduce their side effects. this narrative review, we comprehensively summarized species purified isolated from plants, targets

Language: Английский

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Understanding the impact of valproate on male fertility: insights from preclinical and clinical meta-analysis

BMC Pharmacology and Toxicology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Sept. 27, 2024

Language: Английский

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Valproate discontinuation in girls and women of childbearing age with epilepsy: An Italian multicenter retrospective study on prescribing patterns and outcomes

Epilepsia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Objective This study aimed to identify prescribing behaviors in women of childbearing potential (WOCP) with epilepsy already taking valproate (VPA), and investigate the relationship between VPA maintenance, substitution, reduction, or withdrawal as part polytherapy, seizure worsening relapse. Methods We retrospectively reviewed prescription outcomes WOCP (16–50 years age) epilepsy, referred eight Italian centers, who were for at least 1 year 2014 2019. Results Among 750 (~12% all WOCP), 528 (70.4%) maintained unchanged throughout observation period, 103 (13.7%) replaced another antiseizure medication (ASM), 90 (12%) reduced VPA, 29 (3.9%) discontinued polytherapy. Focal was most strongly associated (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.38–6.38), whereas generalized its non‐withdrawal (reduction/switch/maintenance) (OR .31, CI .14–.68). Intellectual disability, higher frequency, doses linked continuation. from polytherapy a risk tonic–clonic 2.91, 1.09–7.77) compared non‐withdrawal. Significance rarely withdrawn substituted secondary tertiary care settings following European regulatory restrictions. likely reflects population severe epilepsies where is difficult replace; milder earlier, evidenced by low overall frequency. Withdrawal regimen threefold increased exacerbation.

Language: Английский

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ABCB1 c.3435 C > T (rs1045642) as a biomarker for carbamazepine efficacy and toxicity in Algerian patients with epilepsy: initial findings report

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 15, 2025

Language: Английский

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An observational comparative study on the immediate, deferred, and no use of antiepileptics in the management of seizure

International Journal of Basic & Clinical Pharmacology, Journal Year: 2025, Volume and Issue: 14(2), P. 241 - 247

Published: Feb. 25, 2025

Background: The rationale for starting AEDs in patients with seizure and early epilepsy is still unclear. decision to start stop the drugs single seizures remains controversial. This study aims compare efficacy, safety, short-term outcome of immediate, deferred, no use presenting seizure. Methods observational study, included 87 either gender or age group first multiple investigate AED use. Detailed demographics, history, diagnostic test reports were recorded. Drug patterns outcomes recurrence safety evaluated. Results: Out (56 male, 31 female), there 26 paediatrics, 47 adults, 15 elderly. Immediate treatment was given 75%, 16% 9% received no/SOS AED. Levetiracetam commonly prescribed (78% ED, 86% wards, 63% at discharge). For immediate AEDs: 49% had good control, 25% recurrence, breakthrough seizures. Deferred showed 36% control/recurrence 7% breakthrough. Without control recurrence. AEs higher (42%) vs. deferred (15%). Conclusions: indicates that antiepileptic (AEDs) reduces but may increase adverse effects. In cases reversible causes, it be best forgo AEDs. Decisions regarding therapy should tailored patient's preferences risk considerations.

Language: Английский

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Antiseizure potential of the triple T‐type calcium channel blocker ACT‐709478 (apinocaltamide) in rodent models

Epilepsia, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

T-type Ca2+ channels in the brain contribute to generation of spike-and-wave discharges (SWDs). Absence seizures are defined by occurrence SWDs and associated with impairment consciousness. ACT-709478 is a selective highly potent blocker low-voltage-activated channels, Cav3.1, Cav3.2, Cav3.3, no relevant activity on other targets. Our aim was investigate efficacy reducing absence-like types rodents. We studied effect oral two models epilepsy, Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats Genetic Epilepsy Rats Strasbourg (GAERS), compared it first-line monotherapy. also assessed potential reduce generalized convulsive audiogenic seizure-sensitive (AGS) mice maximal electroshock threshold test (MEST) mice, as well one model focal onset seizures, amygdala kindling rat model. tested combinations broadly used medication valproate AGS mice. suppressed WAG/Rij GAERS equivalent or superior that reduced severity mouse MEST albeit at higher concentration. had synergistic effects against when combined valproate, seizures. Based its profile rodent models, represents promising drug candidate for treatment absence epilepsy such childhood syndromes featuring SWDs. It could possibly be beneficial epileptic presenting additional seizure types.

Language: Английский

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Personalised selection of medication for newly diagnosed adult epilepsy: study protocol of a first-in-class, double-blind, randomised controlled trial

BMJ Open, Journal Year: 2025, Volume and Issue: 15(4), P. e086607 - e086607

Published: April 1, 2025

Introduction Selection of antiseizure medications (ASMs) for newly diagnosed epilepsy remains largely a trial-and-error process. We have developed machine learning (ML) model using retrospective data collected from five international cohorts that predicts response to different ASMs as the initial treatment individual adults with new-onset epilepsy. This study aims prospectively evaluate this in Australia randomised controlled trial design. Methods and analysis At least 234 adult patients will be recruited 14 centres Australia. Patients 1:1 ML group or usual care group. The receive ASM recommended by unless it is considered contraindicated neurologist. selected neurologist alone. Both patient neurologists conducting follow-up blinded assignment. groups followed up 52 weeks assess outcomes. Additional information on adverse events, quality life, mood use healthcare services productivity validated questionnaires. Acceptability also assessed. primary outcome proportion participants who achieve seizure-freedom (defined no seizures during 12-month period) while taking initially prescribed ASM. Secondary outcomes include time failure, first seizure after randomisation, changes assessment score life score, direct costs, loss period. provide class I evidence effectiveness decision support tool select Ethics dissemination approved Alfred Health Human Research Committee (Project 130/23). Findings presented academic conferences submitted peer-reviewed journals publication. Trial registration number ACTRN12623000209695.

Language: Английский

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Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal‐onset seizures: A phase III randomized, double‐blind, placebo‐controlled trial

Epilepsia Open, Journal Year: 2024, Volume and Issue: 9(3), P. 1007 - 1020

Published: April 4, 2024

Abstract Objective Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal‐onset seizures (FOS). Methods Phase III, randomized, double‐blind, placebo‐controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day 200 (≥16–80 years) FOS with/without secondary generalization (focal to bilateral tonic–clonic seizures) despite current treatment 1 or 2 concomitant antiseizure medications. Following an 8‐week baseline, were randomized 1:1:1 placebo, mg/day, entered a 12‐week period. Efficacy outcomes: percent reduction over placebo 28‐day frequency (primary); 50% responder rate frequency; median from baseline; seizure freedom during period (secondary). Primary safety endpoints: incidences treatment‐emergent adverse events (TEAEs); TEAEs leading discontinuation; serious TEAEs. Results In this study, 448/449 (mean age, 34.5 years; 53.8% female) received ≥1 dose medication (placebo/BRV mg/BRV mg/day: n = 149/151/148). Percent adjusted was 24.5% ( p 0.0005) 33.4% < 0.0001) respectively, 19.0%, 41.1%, 49.3% respectively 0.0001 for both groups vs. placebo). Median baseline 21.3%/38.9%/46.7% on placebo/BRV respectively. Overall, 0, 7 (4.6%), 10 (6.8%) classified as seizure‐free the 0.0146/ 0.0017 mg/200 respectively). TEAE similar between (58.4%) all receiving (58.5%); 57.0% 60.1%, 0.7% 2.0% reported (incidences 1.3% 2.7%, respectively), 20.1% 33.1% drug‐related 26.5% 39.9%, 4.7% 3.0% discontinued due (discontinuation 2.6% 3.4%, Significance Adjunctive efficacious well tolerated FOS. profiles consistent studies predominantly non‐Asian populations. Plain Language Summary Brivaracetam is used treat partial focal people epilepsy. Most tablets have involved racial backgrounds. 449 adults epilepsy took part. One third mg brivaracetam, one each day 12 weeks. On average, those who had fewer than given placebo. side effects mild number type seen expected medication.

Language: Английский

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Trends in Antiseizure Medication Initiation, Switch, or Termination in Patients With Newly Diagnosed Epilepsy

Neurology, Journal Year: 2024, Volume and Issue: 103(2)

Published: June 18, 2024

Few studies evaluate physicians' choice of antiseizure medication (ASM) to treat patients with newly diagnosed epilepsy. The objective this study was analyze the ASM and its use by age, sex, psychiatric comorbidities, concurrent treatment other drugs (antidepressant medications contraceptives) in who initiated epilepsy using monotherapy.

Language: Английский

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