Search Results (280)

Background: Acute drug poisoning is one of the leading causes of admission to pediatric emergency departments and represents a significant public health concern because of its potential severity and associated morbidity and mortality. This study aimed to describe the clinical, epidemiological, and severity characteristics of pediatric patients with acute drug poisoning treated at a tertiary care hospital in western Mexico. Methods: A retrospective, observational, descriptive study was conducted in the pediatric emergency department of Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” from January 2016 to December 2024. Results: The mean age of the patients was 77.1 months, with a predominance of females (61.9%). Most poisoning events (97.1%) occurred in the home. Accidental poisoning was the most frequent mechanism (54.5%), followed by suicide attempts (24.4%) and drug overdoses (17.6%). Regarding medical care, 50% of patients arrived at the emergency department within the first four hours after exposure, and 55.1% had a hospital stay of less than 12 h. The most involved drug groups were anxiolytics, mainly benzodiazepines (21.6%), followed by polypharmacy (17.6%) and antiemetic use (13.6%). The most frequent toxidrome was hypnotic–sedative syndrome (42.6% of cases). Multivariate analysis showed that exposure to anticonvulsants was significantly associated with a longer hospital stay (odds ratio [OR] = 7.31, p = 0.003). Most cases were classified as mild according to the Poisoning Severity Score, and no deaths were reported. Conclusions: Although pediatric drug poisoning generally has a favorable prognosis, it remains a significant public health issue. These findings highlight the need for targeted preventive strategies, including caregiver education, safe medication storage at home, and increased awareness and training programs for both families and healthcare professionals. Full article

In this study, we assessed the impact of repeated valproate administration on its anticonvulsant effects and side effects in mice. We measured the plasma and brain concentrations of valproate and examined changes in the expression of selected genes in the mouse hippocampus after both acute and chronic treatments. Electroconvulsions were induced using an alternating current (50 Hz, 25 mA, 0.2 s) through ear clip electrodes. Motor impairment and long-term memory deficits were assessed with the chimney test and passive avoidance task. Valproate concentrations in the brain and plasma were measured by a fluorescence polarization immunoassay. mRNA was isolated using a modified Chomczyński and Sacchi method, and RQ-PCR was performed with an Applied Biosystems 7900 using SDS and RQ Study software. The 50% effective dose (ED₅₀) of valproate in the 14 × 2 protocol was significantly lower than the control. Despite no observed memory deficits in chronic protocols, the 50% toxic dose (TD₅₀) for motor impairment was also significantly lower. Chronic valproate treatment did not alter the plasma and brain concentrations. However, the expression levels of three genes (CACNA1G, GAD1, SCN1A) were significantly higher in the chronic protocols with the higher dose of valproate compared to single protocols, suggesting a dose-dependent effect. The repeated administration of valproate resulted in both enhanced efficacy and increased toxicity in terms of motor impairment. The observed effect may be associated with transcriptional adaptations potentially mediated by epigenetic mechanisms rather than with pharmacokinetic events. To enhance the reliability of the results obtained in animal epilepsy models, antiepileptic drugs should be administered chronically. Full article

Benzodiazepines (BZDs) are among the most widely prescribed psychotropic drugs in modern healthcare, primarily used as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. However, rising global consumption and prolonged use raise significant concerns about safety and dependence. Recent studies report that up to 35.8% of patients continue BZD therapy beyond three months, with long-term use observed in over 5% of the general population. These patterns highlight the need for evidence-based strategies to improve prescribing practices. BZDs are recommended primarily for short-term management of severe anxiety or transient insomnia, typically limited to 2–4 weeks. In anxiety disorders, SSRIs and SNRIs are first-line treatments. BZD use is particularly discouraged in older adults due to increased risks of cognitive impairment, falls, and dependence. Rational prescribing requires individualized assessment, minimal effective dosing, gradual withdrawal protocols, and patient education. Enhanced regulatory oversight and improved access to psychotherapy are essential for safer benzodiazepine use. Full article

Introduction: Spontaneous and recurrent epileptic seizures cause neuroinflammation, whereas the chronic administration of antiepileptic drugs may lead to hepatotoxicity and nephrotoxicity. Investigating natural compounds such as naringenin, which exhibits antioxidant, anti-inflammatory, and neuroprotective properties, could mitigate these toxic effects. However, whether naringenin delays seizure onset through anti-inflammatory mechanisms remains unclear. Objective: We evaluated the anticonvulsant effect of subchronic naringenin administration and its impact on inflammatory biomarkers in rats. Methods: Thirty-two male Wistar rats were divided into four groups (n = 8 each): vehicle (10% DMSO), naringenin (50 mg/kg), naringenin (100 mg/kg), and diazepam (4 mg/kg). Treatments were administered once daily for ten days through the intraperitoneal route. On day 11, status epilepticus (SE) was induced via the lithium-pilocarpine model. One hour after SE onset, cardiac blood was collected, and the serum was analyzed via ELISA to quantify the following inflammatory markers: superoxide dismutase (SOD), C-reactive protein (CRP), carbonyl protein, and nitrite/nitrate. Results: We found that 100 mg/kg naringenin increased the latency to SE and the first generalized seizure and shortened the duration of generalized seizures. Fifty percent of the rats in the 100 mg/kg naringenin group did not develop SE. The group treated with 100 mg/kg naringenin demonstrated reduced levels of CRP, protein carbonyls, and nitrates; conversely, the inhibition of SOD activity increased. Conclusions: Naringenin exerted anticonvulsant activity associated with a reduction in oxidative stress and inflammatory plasma biomarkers, suggesting its potential utility in the future development of alternative treatments to reduce epilepsy symptoms. Full article

Background/Objectives: This study aimed to evaluate the frequency and predictors of adverse drug events (ADEs) related to medication abuse, misuse, and dependence, along with serious adverse events (SAEs), and to develop machine learning models to detect serious abuse, misuse, and dependence cases. Methods: This study included 455,415 ADE reports involving medications with high dependence potential reported to the Korea Adverse Event Reporting System (KIDS KAERS DB) between 2013 and 2022. Multivariate logistic regression was used to identify predictors. Three machine learning algorithms, random forest (RF), support vector machine, and eXtreme Gradient Boosting, were developed and evaluated. Results: Higher reporting likelihood of abuse-, misuse-, and dependence-related ADEs was observed with concomitant use of acetaminophen (OR 3.60, 95% CI 2.40–5.39), antidepressants (OR 1.75, 95% CI 1.17–2.61), antipsychotics (OR 4.97, 95% CI 3.21–7.17), and anticonvulsants (OR 3.42, 95% CI 2.42–4.81). Reports from the general public were associated with higher odds of abuse, misuse, and dependence than those from healthcare professionals (OR 4.59, 95% CI 3.04–6.94). Ketamine (ROR 14.03) and bromazepam (ROR 13.02) showed the highest likelihood of being classified as SAEs. Cardiovascular (ROR 30.36) and respiratory disorders (ROR 17.03) demonstrated the highest SAE reporting likelihood. RF model demonstrated the best predictive performance (AUC-ROC 0.928; accuracy 94.4%), with reporter type identified as a key feature. Conclusions: RF model demonstrated optimal predictive performance, with reporter type as the most important feature for detecting serious cases. This study emphasizes the importance of incorporating patient-reported data and polypharmacy surveillance to facilitate early detection of serious cases. Full article

Currently, poly- and monophenol antioxidants should be considered not only as inhibitors that interact with free radicals, but also take into account that they are biologically active substances that affect specific targets in cells and can induce the activity of certain genes or stimulate various signaling pathways. The phenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. In our present study the effect of two antioxidants, sterically hindered monophenols sodium anphene (ANa) and potassium phenosan (PhK), on cell apoptosis of splenocytes was studied by fluorescence and confocal microscopy. PhK has already been introduced into medical practice in the Russian Federation because it proved effective as an anticonvulsant and was useful in treating neonatal hypoxia. The study of ANa continues; it may be a promising anticancer drug for some types of tumors. The fluorescent and confocal microscopy methods demonstrate that ANa in combination with H₂O₂ enhances apoptosis in suspension of Lewis carcinoma cells and to a lesser extent in splenocyte culture. We also discovered that autofluorescence of FAD and immunofluorescence of NADPH enzymatic complexes (with the AV-FITC fluorophore) in splenocytes of normal cells increases symbatically. The autofluorescence of FAD in splenocytes of Lewis carcinoma cells significantly exceeded that of splenocytes of healthy animals. The exact distinctive result was obtained when using potassium phenozan. It turned out that PhK prevents the development of apoptosis in mouse splenocyte cell culture (F1(CBA×C57B)). The combined use of ANa and PhK had no effect on splenocyte apoptosis. We show that fluorescence and confocal microscopy allow observing and quantifying the apoptotic effect of ANa and hydrogen peroxide, and make it possible to visualize metabolic changes in the cell, increased FAD fluorescence in tumor cells and NADPH -oxidase complexes in splenocytes. The data obtained indicate the possibility of using ANa in combination with hydrogen peroxide as an antitumor drug acting on certain types of cells. The different effects of sterically hindered monophenols ANa and PhK on the level of the anti-apoptotic protein Bcl-2 in the cell were established. ANa acts to lower Bcl-2 levels, signaling apoptosis, while PhK prevents the development of apoptosis and induces repair processes. Full article

The development of novel antiepileptic agents requires early identification of pharmacokinetic limitations to mitigate risks at later stages. This study aimed to perform in silico profiling of a library containing 448 novel 2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-2-one derivatives to select lead compounds with an optimal balance of safety and efficacy. The study was conducted using the ADMET-AI platform, based on a graph neural network, to predict physicochemical, pharmacokinetic, and toxicological properties. The methodology involved calculating drug-likeness descriptors for primary screening and a comparative statistical analysis of the top 20 selected structures against 16 approved antiepileptic drugs and four reference compounds. Based on drug-likeness descriptors and predicted ADMET (absorption, distribution, metabolism, excretion, toxicity) related parameters, 20 structures were prioritized for further analysis. Their predicted profiles suggested high intestinal absorption and blood–brain barrier (BBB) permeability, which may be relevant for central nervous system (CNS) directed agents. In comparison with the reference thiazolidinones, the prioritized compounds showed comparatively more favorable predicted mutagenicity and carcinogenicity profiles. Elevated predicted risks of hepatotoxicity and cardiotoxicity were observed for several structures, indicating the need for further structural optimization. The results suggest that the thiopyranothiazolidinone scaffold merits further anticonvulsant-oriented investigation at the stage of early compound prioritization. Experimental validation will be required to confirm the actual pharmacokinetic, toxicological, and anticonvulsant properties of the prioritized compounds. Full article

Epilepsy is a neurological disorder characterized by a long-lasting predisposition to recurrently generate unprovoked seizures. Epilepsy affects over 70 million people worldwide, with approximately one-third suffering from pharmacoresistant seizures. Currently, the clinical antiseizure drugs lack efficacy in preventing epileptogenesis. Adenosine, as an endogenous anticonvulsant, inhibits the development of epilepsy via interaction with the molecular epileptogenic network on several levels: (i) Activation of A1 receptor inhibits glutamate release via presynaptic inhibition, and hyperpolarizes the synaptic potentials in postsynaptic neurons. (ii) The A2A receptor on astrocytes interacts with astroglial glutamate transporter GLT-1, controlling glial glutamate homeostasis. (iii) Activation of the A3 receptor inhibits GABA transporter type 1-mediated GABA uptake. (iv) Adenosine kinase (ADK) is highlighted as a pathological hallmark of epilepsy, with its distinct isoforms driving different mechanisms. The cytoplasmic short isoform (ADK-S) in astrocytes controls extracellular adenosine and receptor-mediated pathways, whereas the nuclear long isoform (ADK-L) in astrocytes and specific neurons regulates epigenetic mechanisms without relying on adenosine receptors. Collectively, this review clarifies the adenosine system’s critical regulatory role in the epileptogenic network, highlights adenosine receptors and ADK isoforms as promising therapeutic targets for epilepsy, and provides a theoretical basis for developing novel disease-modifying therapies for pharmacoresistant epilepsy while laying a foundation for subsequent preclinical and clinical translation. Full article

The gut microbiota’s (GM) regulation of inflammation and oxidative stress is supported by existing evidence, and its dysregulation relates to brain disease. Indeed, probiotics and prebiotics have been shown to improve cognitive function. This is associated with a stronger gut and blood–brain barrier and less gut inflammation. Oligofructose-enriched inulin alters the GM, reduces body fat, and lowers interleukin-6 (IL-6) in obese patients. Moreover, by increasing glutathione (GSH), the ketogenic diet (KD) prevents seizures and also benefits the intestinal short-chain fatty acid (SCFA) profile. Given the evidence on managing epileptic conditions, the aim of this review is to assess how changing the gut microbiota (GM) can be a therapeutic method for preventing neurodegenerative dysfunctions associated with epileptic seizure onset and progression, with a focus on innovative supplement strategies, including endogenous and exogenous antioxidants, nutrition, and new phyto-therapies. Indeed, though drugs are the main treatment for epilepsy, the KD and other supplements are increasingly being considered. These compounds affect neuronal excitability, neurotransmitter release, and neuroinflammation, thus providing an anticonvulsant effect. Specifically, the KD prevents seizures by increasing GSH levels, which represents a crucial endogenous antioxidant that plays a key role in counteracting neuroinflammation and gut microbiota dysfunction. Furthermore, due to their antioxidant and anti-inflammatory properties, plant extract derivatives may be new agents that could reduce neuroinflammation in seizures, affecting the gut–brain axis (GBA) through the intestinal microbiota. In conclusion, data suggest that further clinical studies are needed to explore how the GM impacts epilepsy, and how specific nutraceuticals might offer probiotic benefits. Thus, a combined effect of nutraceuticals and functional food might be appealing, potentially resulting in a more beneficial therapeutic outcome. Full article

Background/Objectives: Lamotrigine is an anticonvulsant and mood stabilizer with wide interindividual pharmacokinetic variability, necessitating therapeutic drug monitoring (TDM). Patient-based quality control (PBQC) strategies, such as tracking median drug concentrations, may complement traditional quality assurance in routine laboratory practice. Methods: We retrospectively analyzed 15,963 lamotrigine results collected between February 2011 and December 2025 at Uppsala University Hospital, Uppsala. Data included age, sex, sampling date, and lamotrigine concentrations. Assays were performed using the Architect platform from February 2011 to January 2021, after which the Cobas Pro c 503 platform was implemented. Yearly patient medians were calculated, and trends, seasonal variation, and method agreement were assessed. Results: Of all the results, 5967 were from males and 9996 from females. Median concentrations were slightly higher in males (15.20 µmol/L) than in females (13.71 µmol/L), representing a weak but statistically significant difference (Spearman R = −0.048; p < 0.0001). The total number of reported results increased steadily over time, from 402 in 2011 to more than 1500 annually by 2024–2025. Median lamotrigine concentrations increased from 11.85 µmol/L in 2011 to 17.40 µmol/L in 2025 (Spearman R = 0.047; p < 0.0001). Seasonal variation in sample volume was observed, with peaks in November and troughs in July and December, but median concentrations remained stable (CV = 3.49%). Method comparison showed strong agreement between Architect and Cobas assays (R² = 0.97). Conclusions: Patient median lamotrigine concentrations serve as a robust PBQC tool, capable of detecting subtle analytical shifts while remaining resilient to seasonal fluctuations and platform transitions. This approach enhances confidence in assay reliability and supports safer therapeutic decision-making in real-world TDM practice. Full article

Chemotherapy-induced neuropathic pain (CINP) can be caused by several chemotherapeutic drugs, including paclitaxel, oxaliplatin, and vincristine, which is difficult to treat with several drugs, including antidepressants and anticonvulsants. The patho-mechanisms of CINP are not completely understood. However, they showed oxidative stress, mitochondrial damage, ion channel damage, and immunological dysfunction. Acting as a key regulator of antioxidant responses, nuclear factor erythroid 2-related factor 2 (Nrf2) decreased oxidative stress and mitochondrial damage. In addition, it plays a role in inhibiting nuclear factor kappa B (NF-κB). A systematic, English-only search of MEDLINE (PubMed) was performed for studies on Nrf2, chemotherapy, and neuropathic pain from database inception through 1 December 2024. Several Nrf2 activators, including tempol, oltipraz, rosiglitazone, pristimerin, cannabidiol, daidzein, bardoxolone methyl, curcumin, resveratrol, and mitoquinone, demonstrated analgesic effects in CINP animal models. Furthermore, in clinical studies, curcumin demonstrated significant efficacy in reducing vincristine-induced neuropathy in pediatric leukemia patients, while the combined administration of alpha-lipoic acid with ipidacrin hydrochloride prevented paclitaxel-induced motor neuropathy and improved axonal function in breast cancer patients. Thus, the purposes of our review article were to summarize the analgesic effects of Nrf2 activators and the patho-mechanisms of Nrf2 in CINP animal, and then the consequences for clinical trials were presented. Full article

Background: Epilepsy comprises a range of disorders affecting the central nervous system (CNS) characterized by recurrent seizures, impacting approximately 60 million individuals globally. In this study, we designed and derived a series of peptide analogs 1–30 of 3,4,5-trimethoxycinnamic acid (TMCA) from the herbal combinations of Polygala tenuifolia and Gastrodia elata, recognized in Traditional Chinese Medicine (TCM). Methods: All the analogs were synthesized, and their anticonvulsant efficacy was subsequently assessed. The anticonvulsant activity of all TMCA analogs was evaluated using two acute seizure models in mice: the maximal electroshock (MES) and the sc-pentylenetetrazole (PTZ) models. Furthermore, we explored the electroencephalogram (EEG) and double-labeling immunofluorescence experiments were carried out as well. Results: Our findings indicated that compounds 11, 19, 22, and 23 demonstrated favorable anticonvulsant activities during the initial assessment. Compounds 19 and 23 also played roles in controlling the onset of epilepsy in EEG, modulating levels of GABA aminotransferase (GABA-AT)/gamma-aminobutyric acid type A receptor (GABA_AR), interacting with active sites of GABA-AT and GABA_AR obtained from docking simulation methods. Conclusions: Novel derivatives in this study provide new cores for further design and optimization inspired by TCM herb pair drugs P. tenuifolia and G. elata, with the aim of exploring new anticonvulsant agents. Full article

Background/Objectives: Trigeminal Neuralgia (TN) is a chronic neuropathic condition characterized by sudden, severe facial pain. Anticonvulsants are the cornerstone of pharmacological management, yet comparative evidence based on pharmacological class remains scarce. This systematic review aimed to evaluate the efficacy and safety of anticonvulsants in TN, stratified by their mechanism of action. Methods: A systematic search in PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines. Studies employing a pharmacological approach including human patients with TN, published in English since 2000, were included. Risk of bias was assessed using the Cochrane RoB 2, the ROBINS-I and the ROBINS-E tools, according to the study design. Results: Out of 922 initial records, 12 studies met the eligibility criteria. Sodium channel inhibitors showed high efficacy but frequent adverse effects, particularly hyponatremia and central nervous system symptoms. Calcium channel modulators offered a more favorable safety profile. Combination therapies showed benefits, levetiracetam and topiramate were moderately effective and well tolerated. Although the evidence has limitations, anticonvulsants continue to be the primary treatment for TN. Sodium-channel blockers demonstrate strong efficacy, whereas alternative agents generally provide superior tolerability. Conclusions: These findings support selecting drugs according to their underlying mechanisms of action. Equally important is tailoring therapy to pain phenotype and patient characteristics, balancing mechanism with tolerability and efficacy. Full article

Canine epilepsy often resists conventional antiepileptic drugs (AEDs), which affects their quality of life. Cannabidiol (CBD) has anticonvulsant properties; however, evidence of its use in canine epilepsy is limited and contradictory. This prospective pilot study aimed to investigate the potential advantages, safety profile, and effects of CBD on quality of life when used as an adjunctive therapy in cases of drug-resistant epilepsy in canines. Thirteen dogs with refractory epilepsy, all on 2–6 concurrent AEDs, were enrolled. A single-arm pretest–post-test design was used. CBD was titrated from 0.5 mg/kg BID 2.5 mg/kg q12h. The primary outcome was the change in seizure frequency. Secondary outcomes included changes in seizure severity, seizure cluster, hematological and biochemical parameters, and owner-reported quality of life (QoL). Significant overall seizure frequency reduction (p = 0.02) with the median decreased from 11 (IQR 9–22) during the pre-intervention period to 5 (IQR 2–13) at the post-intervention follow-up. Notably, 61.5% of the dogs achieved a ≥50% reduction in seizure frequency. The number of seizure clusters was significantly decreased (p = 0.001). Most hematological/renal parameters remained stable; however, Alkaline Phosphatase (ALP) levels significantly increased (p < 0.001). The owners reported positive CBD perceptions and an improved quality of life. CBD shows the potential for refractory canine epilepsy, especially in clusters. Increased hepatic enzyme levels necessitate rigorous monitoring, particularly with the concurrent use of AEDs. This groundbreaking study explored the application of CBD in managing canine epilepsy, utilizing a “start-low, go-slow” strategy to minimize adverse effects while effectively controlling seizures. Our findings underscore the necessity of customizing CBD dosages for individual needs and highlight the critical importance of monitoring liver function. This study challenged the traditional one-size-fits-all dosing approach. It provides the first evidence and practical framework for the use of CBD to treat canine epilepsy in Asia, detailing the pioneering approach and the initial findings from this cohort. Full article

Background/Objectives: Epilepsy is a major neurological disorder associated with significant comorbidity and treatment challenges. In low- and middle-income countries, access to newer antiseizure medications (ASMs) remains limited, and prescription patterns often rely on older agents. This study aimed to characterize national prescribing patterns of ASMs among patients with epilepsy in Kazakhstan from 2021 to 2023. Methods: We conducted a retrospective observational study using de-identified electronic health record data from the Unified National Electronic Health System of Kazakhstan. All patients with an ICD-10 diagnosis of epilepsy (G40) and at least one ASM prescription during 2021–2023 were included. Prescription frequencies, therapy type, and chronic polytherapy levels were analyzed. Associations between therapy type, age, and comorbidity status were determined. Results: A total of 54,274 patients were identified (median age 42 years; interquartile range (IQR) 31–57). Monotherapy predominated: 61.7% remained on monotherapy, 18.5% remained on polytherapy, and 19.8% had mixed exposure. Carbamazepine and valproic acid were most frequently prescribed (64.3% and 45.6% of patients, respectively). Among those with chronic medication data (n = 15,752), nervous-system drugs were common (70.1%), led by psycholeptics (49.7%); frequently dispensed agents included chlorpromazine (n = 5991), clozapine (n = 1875), and risperidone (n = 1642). Cardiovascular agents were recorded in 37.2% (acetylsalicylic acid n = 4056; atorvastatin n = 2235), and diabetes drugs in 12.1% (metformin n = 1430). Conclusions: Epilepsy treatment in Kazakhstan remains dominated by older broad-spectrum ASMs, while the use of lamotrigine and levetiracetam is steadily increasing. The frequent co-prescription of psychotropic and cardiometabolic drugs underscores the need for coordinated, multidisciplinary care and continued monitoring of prescribing patterns to enhance treatment safety and effectiveness. Full article