Anticonvulsant Activity Research Articles

Ethnobotany, Phytochemistry, Pharmacology and Therapeutic Potential of Su‘ad Kūfī (Cyperus rotundus L.): An Insight

Background: Cyperus rotundus, an important medicinal plant belonging to the Cyperaceae family, is therapeutically used in many traditional systems of medicine, such as Unani medicine, Ayurveda, Siddha, Homeopathy, Chinese medicine, etc. Aim: The prime goal of this review is to provide a scientific basis and classical references for clinical use and further scientific exploration of Cyperus rotundus. Materials and Methods: This systemic review was carried out after searching Unani classical and other ethnobotanical literature and published research work available on PubMed, SCOPUS, Science Direct, Google Scholar, Research Gate, etc. Results: Cyperus rotundus L. is the accepted botanical name of Su'ad Kūfī, Nagarmotha, or Nutgrass as referred in Unani and other traditional medicines. It is grown in India, China, the Philippines, Thailand, Taiwan, Indonesia, Korea, Vietnam, Malaysia, the Pacific Islands, South America, Africa, the Middle East, North America, Mexico, Australia, New Zealand, and Europe. Usually, the rhizome of this important medicinal plant is therapeutically used for various ailments, including indigestion, constipation, dysentery, neurogenic gastralgia, skin diseases, mental weakness, cardiac weakness, nervine weakness, palpitation, weakness of stomach, flatulence, retention of urine, amenorrhea, dribbling of urine, etc. It contains many important secondary metabolites, including flavonoids, tannins, glycosides, monoterpenes, sesquiterpenes, sitosterol, alkaloids, saponins, terpenoids, essential oils, sugar, protein, amino acids, etc., which have been reported to possess antibacterial, anti-tumour, anticonvulsant, antidiabetic, anti-diarrhoeal, anti-inflammatory, antilipidemic, antimalarial, anti-obesity, antioxidant, hepatoprotective, cardioprotective, and neuroprotective pharmacological activities. Conclusion: It is concluded that abundant bioactive compounds identified and separated from Cyperus rotundus possess potential medicinal values on different systems of the body.

Design, Synthesis and in-vivo Anticonvulsant activity of Some Novel Coumarin Derivatives

Design, Synthesis and in-vivo Anticonvulsant activity of Some Novel Coumarin Derivatives

Magnesium sulphate: Current application in anaesthesia

The role of magnesium in medicine has advanced considerably over the two decades. It is now generally accepted that magnesium is a crucial nutrient, and its deficiency has adverse effects on a variety of physiological processes. Magnesium deficiency should be avoided in the perioperative period. Magnesium has been developed as a drug with various clinical uses. It is a key cation in physiological processes, and its homeostasis is essential for the normal function of human body organs. Magnesium sulphate is a mineral pharmaceutical preparation of magnesium. It has a high therapeutic index and cost-effectiveness. Magnesium sulphate is readily available, affordable and its use in clinical practice is associated with less complications. Recently, the potentiation of effects of muscle relaxation and perioperative analgesia has drawn the attention of anaesthetists to the use of magnesium sulphate in anaesthesia and pain management. The characteristics features of magnesium sulphate as a vasodilator, ability to protect the blood brain barrier, reduction of cerebral oedema and central anticonvulsant action make it very useful in intensive care.

New triazole-based hybrids as neurotropic agents.

Herein, we describe the synthesis of new hybrids linked to 1,2,3- and 1,2,4-triazole units. Hybrids connected to a 1,2,3-triazole ring were synthesized using the well-known click reaction. The synthesis of the 1,2,4-triazole-based hybrids was carried out using 2-[(4-cyano-1-methyl(2-furyl)-5,6,7,8-tetrahydroisoquinolin-3-yl)oxy]acetohydrazides as starting compounds. The compounds were evaluated for their anticonvulsive activity via antagonism towards pentylenetetrazole (PTZ) - and thiosemicarbazide (TSC)-induced convulsion and maximal electroshock-induced seizure (MES). Furthermore, the most active compounds were studied for their locomotory and anxiolytic activity via the "open field" and elevated plus maze (EPM) assays. Finally, their antidepressant activity was studied via the "forced swim" method. All the hybrids displayed pentylenetetrazole antagonism, ranging from 40% to 80%, while in the TSC model, the most active compounds increased latency of thiosemicarbazide seizures to 1.9-4.65 times compared to that of the control. Some of the tested compounds exhibited a pronounced anxiolytic and antidepressant effect. Docking study demonstrated complete agreement with experimental pharmacological data. It was revealed that the most active compounds have a pyrano[3,4-c]pyridine ring in their structure.

Comprehensive Review on Nilofar (Nymphaea alba Linn): Unani Perspectives and Therapeutic Potentials

Nilofar (Nymphaea alba Linn) is commonly known as the white-water lily. It is a hydrophyte with enormous medicinal properties, renowned for its alluring white flowers. It is distributed worldwide in ponds, lakes, and marshy areas. Its various parts have been extensively utilized in Unani medicine globally, particularly in the Indian subcontinent, to prevent and treat a variety of ailments. Numerous research findings have documented its therapeutic effects, including anti-inflammatory, anti-hepatitis C, anti-diarrheal, hepatoprotective, antibacterial, anticarcinogenic, antiurolithiatic, uterotonic, anxiolytic, antidepressant, CNS depressant, anticonvulsant, antihyperlipidemic, and antioxidant activities. In Unani medicine, Nilofar is used to treat various illnesses such as palpitations, diarrhea, hepatotoxicity, inflammation, migraines, anxiety, depression, and convulsions. Nilofar contains a variety of chemical constituents, including alkaloids, tannins, flavonoids, phenolic content, glycosides, aglycons, phenolic acids, cardiac glycoside nymphalin, and others. This review explores the therapeutic potential of Nilofar, shedding light on its pharmacological properties, traditional uses, and emerging research. By combining traditional knowledge with the latest scientific findings, this review aims to encourage further research and facilitate its integration into mainstream healthcare practices.

Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine activity in aged mice.

Alzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults; these seizures, left untreated, may worsen functional decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled mouse model of acquired chronic secondarily generalized focal seizures allows for precisely timed drug administration studies to quantify the efficacy and tolerability of ASMs in an AD-associated genetic model. We hypothesized that mechanistically distinct ASMs would exert differential anticonvulsant activity and tolerability in aged AD mice (8-15 months) to define whether rational ASM selection may benefit specific AD genotypes. Aged male and female PSEN2-N141I versus age-matched non-transgenic control (PSEN2 control) C57Bl/6J mice, and APP swe /PS1 dE9 versus transgene negative (APP control) littermates underwent corneal kindling to quantify latency to fully kindled criterion. Dose-related ASM efficacy was then compared in each AD model versus matched control over 1-2 months using ASMs commonly prescribed in older adults with epilepsy: valproic acid, levetiracetam, lamotrigine, phenobarbital, and gabapentin. Sex and AD genotype differentially impacted seizure susceptibility. Male PSEN2-N141I mice required more stimulations to attain kindling criterion (X 2 =5.521; p<0.05). Male APP/PS1 mice did not differ in kindling rate versus APP control mice, but they did have more severe seizures. There were significant ASM class-specific differences in acute seizure control and dose-related tolerability. APP/PS1 mice were more sensitive than APP controls to valproic acid, levetiracetam, and gabapentin. PSEN2-N141I mice were more sensitive than PSEN2 controls to valproic acid and lamotrigine. AD genotypes may differentially impact ASMs activity and tolerability in vivo with advanced biological age. These findings highlight the heterogeneity of seizure risk in AD and suggest that precisely selected ASMs may beneficially control seizures in AD, thus reducing functional decline.

Synthesis, characterization, anxiolytic and anticonvulsant activity, DFT, molecular docking, DMPK studies of chalcone derived from maleic anhydride

Anxiety typically doesn't cause convulsions, but intense stress can reduce the threshold for convulsive bouts in predisposed individuals. Chalcones are known to act directly on the central nervous system (CNS) and the presence of electron donor and acceptor groups attached to the aromatic rings in various positions can alter the properties of the molecule. Thus, this work investigated the anxiolytic and anticonvulsant potential of the new chalcone derivative (E)-6-(4-((E)-3-(3-nitrophenyl)acryloyl)phenyl)-5-oxohex-2-enoic acid (CAMEL). 1H and 13C NMR and ATR-FTIR analyses helped to determine the molecular structure of this chalcone. The energy gap analysis and the higher hardness values than the softness values confirm the stability of CAMEL, with CGDRs indicating that it is more electrophilic in nature. In relation to its potential anxiolytic effect, the tested dose of 40 mg kg-1 of the derivative showed behavior like Diazepam, with activity via GABAA. In addition, the derivative also exhibited a possible anticonvulsant effect at the dose of 20 mg kg-1, being like Diazepam, showing involvement in stages 2 and 3 of GABAA receptors in this process. Given the anxiolytic and anticonvulsant activity shown in vivo and in silico tests, CAMEL is a promising candidate for the treatment of diseases that affect the CNS.

Schiff Bases: A Captivating Scaffold with Potential Anticonvulsant Activity.

One of the most important organic compounds, also known as a Schiff base, imine, or azomethine, has been associated with several biological processes. The group is a component of both natural or synthetic chemicals and functions as both a precursor and an intermediary in the synthesis of therapeutically active substances. The review highlights the various non-metal Schiff bases' structure-activity relationship (SAR) studies, general model, docking, and design approach for anticonvulsant actions. Schiff bases serve as linkers in numerous synthetic compounds with a variety of activities, according to the findings of several investigations. As a result, the current review will give readers a thorough understanding of the key ideas put forth by different researchers regarding the anticonvulsant properties of Schiff bases. It will serve as a valuable information source for those planning to synthesize new anticonvulsant molecules that contain Schiff bases as pharmacophores or biologically active moieties.

Evaluation of thiopyrano[2,3-d]thiazole derivatives as potential anticonvulsant agents.

Anticonvulsant drug discovery has achieved significant progress; however, pharmacotherapy of epilepsy continues to be a challenge for modern medicine and pharmacy. To expand the chemical space of heterocycles as potential antiepileptic agents, herein we report on the synthesis and evaluation of anticonvulsant properties of a series of thiopyrano[2,3-d]thiazoles. The studied heterocycles are characterized by satisfactory drug-likeness and pharmacokinetics properties, calculated in silico using SwissADME. The anticonvulsant activity of thiopyrano[2,3-d]thiazole derivatives was evaluated in vivo using the subcutaneous pentylenetetrazole test. Three hits, that is, compounds 12, 14, and 16, that caused a pronounced anticonvulsant effect were identified. Derivatives 12, 14, and 16 positively affected the latent period of onset of clonic seizures, number of seizures, mortality rate, and duration of the seizure period of animals under experimental conditions. The anticonvulsant properties of compound 14 were equivalent to the effect of the reference drug, sodium valproate. All hit compounds are characterized by satisfying toxicity properties in the human lymphocytes and HEK293 cell line. The most active hit 14 possesses a potential affinity with the GABAA receptor in the molecular docking study and forms a stable complex in the molecular dynamics experiments equal to diazepam. Preliminary SAR results were obtained and discussed based on screening data.

Unveiling the Multi-Targeted Mode of Action: Investigating the Antiepileptic Activity of Murraya koengii Extract in PTZ-induced Seizures.

Recurrent seizures are the hallmark of the neurological condition known as epilepsy. Murraya koenigii (curry leaves) has been traditionally used in medicine for various ailments. This study aimed at the anticonvulsant activity of HAEMK using a petylenetetrazole (PTZ) induced seizure model. Behavioral and biochemical parameters were assessed to determine the effectiveness of the extract in mitigating seizures. Albino mice were orally administered with different doses of the extract prior to PTZ administration. The behavioral parameters, including seizure latency, duration and severity, were monitored and recorded. Additionally, acetylcholine esterase, GSH, and malondialdehyde (MDA), three indicators of oxidative stress, were assessed in brain tissue homogenates. HAEMK-treated groups demonstrated a substantial increase in seizure latency and a decrease in seizure length and intensity compared to the control group. A dose-dependent MDA and acetylcholine esterase decreased concurrent GSH rise were seen in the HA-treated groups. These findings suggest that the hydroalcoholic extract of M. koenigii possesses antiepileptic activity, possibly mediated through its antioxidative mechanisms.

Moxibustion pre-treatment attenuates seizure severity during status epilepticus and counteracts the proconvulsant function of the purinergic P2X7 receptor.

Moxibustion, traditional Chinese medicine treatment, involves the warming of specific acupuncture points of the body using ignited herbal materials. Evidence suggests beneficial effects of moxibustion in several brain diseases including epilepsy, however, whether moxibustion pretreatment impacts on seizures and what are the underlying mechanisms remains to be established. Evidence has suggested the purinergic ATP-gated P2X7 receptor (P2X7R) to be involved in the actions of moxibustion. Moreover, P2X7R signalling is now well established to contribute to long-lasting brain hyperexcitability underlying epilepsy development. Whether P2X7R signalling is involved in the seizure-reducing actions of moxibustion has not been investigated to date. For our studies we used C57BL/6 male mice that received moxibustion pre-treatments at the acupoints Zusanli (ST36) and Dazhui (GV14) once daily for either 7, 14, or 21days. This was followed by an intraperitoneal injection of kainic acid (KA, 30mg/kg) to induce status epilepticus. Behavioral changes during KA-induced status epilepticus were analyzed according to the Racine scale. Changes in electrographic seizures were analyzed via cortical implanted electroencephalogram (EEG) electrodes. While no effect on seizure severity was observed following 7days of moxibustion pre-treatment, moxibustion pre-treatment at both ST36 and GV14 for 14 or 21days significantly reduced KA-induced behavior seizures at a similar rate. Cortical EEG recordings showed that 14days of moxibustion pre-treatments also reduced electrographic seizures, confirming the anticonvulsant actions of moxibustion pre-treatment. To determine whether moxibustion impacts the pro-convulsant actions of P2X7R signaling, mice were treated with the P2X7R agonist BzATP or P2X7R antagonist A438079. While treatment with the P2X7R agonist BzATP exacerbated seizure severity, treatment with the P2X7R antagonist reduced seizure severity. We further found that moxibustion pre-treatment attenuated epileptic seizures by counteracting the effects ofBzATP. These results suggest that moxibustion pre-treatment at the acupoints ST36 and GV14 for 14days has anti-epileptic effects, which may counteract the proconvulsant functions of the P2X7R.

Development of Novel Alaninamide Derivatives with Anticonvulsant Activity and Favorable Safety Profiles in Animal Models.

In our current study, we developed a focused series of original ((benzyloxy)benzyl)propanamide derivatives that demonstrated potent activity across in vivo mouse seizure models, specifically, maximal electroshock (MES) and 6 Hz (32 mA) seizures. Among these derivatives, compound 5 emerged as a lead molecule, exhibiting robust protection following intraperitoneal (i.p.) injection, as follows: ED50 = 48.0 mg/kg in the MES test, ED50 = 45.2 mg/kg in the 6 Hz (32 mA) test, and ED50 = 201.3 mg/kg in the 6 Hz (44 mA) model. Additionally, compound 5 displayed low potential for inducing motor impairment in the rotarod test (TD50 > 300 mg/kg), indicating a potentially favorable therapeutic window. In vitro toxicity assays further supported its promising safety profile. We also attempted to identify a plausible mechanism of action of compound 5 by applying both binding and functional in vitro studies. Overall, the data obtained for this lead molecule justifies the more comprehensive preclinical development of compound 5 as a candidate for a potentially broad-spectrum and safe anticonvulsant.

Insight into the Various Approaches Undertaken for the Synthesis of Quinoline Hybrids Imparting Diverse Therapeutic Activities

Abstract: Quinoline is one of the promising and prominent biologically active N-based heterocyclic compounds. This review paper aims to discuss the synthetic approaches, summarized from various research articles on the preparation of quinoline derivatives intended for different therapeutic activities like antifungal activity, anticancer activity, anticonvulsant activity, antitubercular activity, antimalarial activity, anti-Alzheimer activity and so on. The comprehensive study complies with all related publications and trademark publications demonstrating the synthesis and biological aspects of quinoline derivatives. Various types of quinoline hybrids were synthesized and treated for therapeutic activity, including anticancer, antitubercular, anti-Alzheimer, antioxidant, and antifungal activity, which have been analyzed. Quinoline is a planner hetero-aromatic compound with the chemical formula C9H7N. Several wellknown synthetic routes to the quinoline skeleton include Friedlander synthesis, Knorr quinoline synthesis, and Skraup reaction. Researchers may use other techniques or alter current strategies to reach their objectives, depending on what exact structure and therapeutic action they are investigating. The availability of starting materials, reaction conditions, scalability, desired regioselectivity, and functionalization of the quinoline core all have a role in the choice of synthetic method. This review covers the latest literature and knowledge on the synthetic procedures for numerous quinoline and its derivatives and their biological and pharmacological application.

In silico Approaches for Exploring the Pharmacological Activities of Benzimidazole Derivatives: A Comprehensive Review.

This article reviews computational research on benzimidazole derivatives. Cytotoxicity for all compounds against cancer cell lines was measured and the results revealed that many compounds exhibited high inhibitions. This research examines the varied pharmacological properties like anticancer, antibacterial, antioxidant, anti-inflammatory and anticonvulsant activities of benzimidazole derivatives. The suggested method summarises In silico research for each activity. This review examines benzimidazole derivative structure-activity relationships and pharmacological effects. In silico investigations can anticipate structural alterations and their effects on these derivative's pharmacological characteristics and efficacy through many computational methods. Molecular docking, molecular dynamics simulations and virtual screening help anticipate pharmacological effects and optimize chemical design. These trials will improve lead optimization, target selection, and ADMET property prediction in drug development. In silico benzimidazole derivative studies will be assessed for gaps and future research. Prospective studies might include empirical verification, pharmacodynamic analysis, and computational methodology improvement. This review discusses benzimidazole derivative In silico research to understand their specific pharmacological effects. This will help scientists design new drugs and guide future research. Latest, authentic and published reports on various benzimidazole derivatives and their activities are being thoroughly studied and analyzed. The overview of benzimidazole derivatives is more comprehensive, highlighting their structural diversity, synthetic strategies, mechanisms of action, and the computational tools used to study them. In silico studies help to understand the structure-activity relationship (SAR) of benzimidazole derivatives. Through meticulous alterations of substituents, ring modifications, and linker groups, this study identified the structural factors influencing the pharmacological activity of benzimidazole derivatives. These findings enable the rational design and optimization of more potent and selective compounds.

Exploring the Bioactive Constituents and Pharmacological Activity of Scutellaria baicalensis Georgi, or Chinese Skullcap

Introduction: Scutellaria baicalensis Georgi, a plant with therapeutic properties, has been extensively utilized in China for centuries. The extract derived from its roots is commonly referred to as Huang-Qin. Materials and Methods: The informative data were gathered from many electronic databases, including Scopus, Science Direct, PubMed, and Web of Science. The study criteria for selection included analyzing scientific manuscripts that specifically investigated phytoconstituents and their pharmacological effects. The keywords used were Scutellaria baicalensis, bioactive components, and pharmacological profile. Discussion: The main concern of this study is to enhance the accessibility of extensive research discoveries about the pharmacological potential of S. baicalensis. Results: S. baicalensis root has been utilized to manage dysentery, diarrhea, hypertension, insomnia, inflammation, respiratory infections, and hemorrhaging. Wogonoside and baicalin are the primary bioactive constituents obtained from S. baicalensis root. The flavones have been documented to possess many pharmacological properties, such as hepatoprotective, anti-cancer, antibacterial, antioxidant, antiviral, neuroprotective, and anticonvulsant activities. Conclusion: This manuscript's main concern is to enhance the accessibility of extensive research discoveries about the pharmacological potential of S. baicalensis.

Coronaridine congeners induce anticonvulsant activity in rodents by hippocampal mechanisms involving mainly potentiation of GABAA receptors

The coronaridine congeners catharanthine and 18-methoxycoronaridine (18-MC) display sedative, anxiolytic, and antidepressant properties by acting on mechanisms involving GABAergic and/or monoaminergic transmissions. Here, we expanded their pharmacological properties by studying their anticonvulsant activity in male and female mice using the pentylenetetrazole (PTZ)-induced seizure test. To determine potential neurochemical mechanisms, the effect of congeners on monoamine content and kainic acid (KA)-induced epileptiform discharge was studied in the hippocampus. The behavioral results showed that coronaridine congeners induce acute anticonvulsant activity in a dose-dependent but sex-independent manner. Repeated treatment with a subthreshold dose (20 mg/kg) of each congener produced anticonvulsant activity in a sex-independent manner, but was significantly higher in male mice when compared to its acute effect. Using a behaviourally relevant regimen, we found that PTZ increased dopamine metabolites and serotonin tissue content. Coronaridine congeners, which induced distinct effects on monoamines, blunted the effect of PTZ instead of potentiating it, suggesting the existence of another mechanism in their anticonvulsant activity. The electrophysiological results indicated that both congeners inhibit KA-induced epileptiform discharges in hippocampal slices. A key aspect of this study is that the activity of both congeners was observed only in the presence of GABA, supporting the notion that hippocampal GABAAR potentiation plays an important role. Our study showed that coronaridine congeners induce acute anticonvulsant activity in a sex-independent manner. However, a comparatively higher susceptibility was observed in male mice after repeated treatment. The underlying hippocampal mechanisms mainly involve GABAAR potentiation, whereas monoamines play a minor role in the anticonvulsive action.

Metformin alleviates reactive gliosis and neurodegeneration, improving cognitive deficit in a rat model of temporal lobe epilepsy

Cognitive impairment is a prevalent co-morbidity associated with epilepsy. Emerging studies indicate that neuroinflammation could be a possible link between epilepsy and its comorbidities, including cognitive impairment. In this context, the roles of glial activation, proinflammatory mediators, and neuronal death have been well studied and correlated with epilepsy-associated cognitive impairment in animal studies. While recent reports have demonstrated the anti-epileptogenic and anti-convulsant actions of metformin, its effect on epilepsy associated cognitive deficit remains unknown. Therefore, the current study investigated the effect of metformin treatment on neuroinflammation, neurodegeneration, and cognitive deficits after inducing status epilepticus (SE) with lithium-pilocarpine in rats. Metformin treatment improved the hippocampal-dependent spatial and recognition memory in Morris water maze and Novel object recognition tasks, respectively. Further, metformin treatment attenuated microglial and astroglial activation, accompanied by reduced IL-1β, COX-2 and NF-ĸβ gene expression. Additionally, metformin conferred neuroprotection by inhibiting the neuronal death as assessed by Nissl staining and transmission electron microscopy. These findings suggest that metformin holds promise as a therapeutic intervention for cognitive impairment associated with epilepsy, possibly through its modulation of glial activation and neuronal survival. Further research is needed to elucidate the precise mechanisms and to assess the long-term effect of metformin in epilepsy-associated cognitive impairment.

Wide-ranging Study on Synthesis and Biological Evaluation of 1, 2, 3-triazole

Abstract: 1, 2, 3-Traizole is five-membered heterocyclic compounds having three nitrogen at 1, 2 and 3 positions. 1, 2, 3-Triazoles are important five-membered heterocyclic scaffolds due to their widespread biological activities. 1, 2, 3-Triazole derivative can be readily obtained in good to excellent yields through click chemistry, 1, 3-dipolar cycloaddition, Metal Catalysed azide-alyne cycloaddition method. 1, 2, 3-Triazoles showed various biological activities, such as antiinflammatory, anticonvulsant, antineoplastic, antimicrobial, analgesic, antimalarial, antiviral, antiproliferative, and anticancer activities. The objective of this review is to synthesize pharmacological activity of 1,2,3-triazole derivatives documented in recent literature.

A Study on the Anticonvulsant Activity of the Simultaneous Administration of Melatonin, Agmatine, and Vitamin D3 on Pentylenetetrazole-Induced Seizures in Mice

Background: Epilepsy is a neurological disorder characterized by a decreased level of vitamins and endogenous antioxidants and an enhanced level of oxidative stress. Objective: We designed this study to define the effects of combining melatonin, vitamin D3 (Vit D3), and agmatine on seizures caused by pentylenetetrazole (PTZ) in male NMRI mice. Methods: The experimental groups were as follows: the first group was administered normal saline (0.5 ml, i.p.) on the last day of the trial, and the second group was administered intraperitoneal PTZ (60 mg/kg) on that day. Pre-treatment with diazepam (4 mg/kg), vitamin D3 (6000 IU/kg, p.o.), agmatine (40 mg/kg, p.o.), and melatonin (20 mg/kg, p.o) was given to the next four groups before injecting PTZ (60 mg/kg, i.p.). The last group received a compound therapy of vitamin D3, melatonin, and agmatine before PTZ injection. Afterward, the latency, duration, and oxidative stress indications were evaluated in the brains of mice. Results: Treatments enhanced the latency of seizure and reduced seizure duration in comparison with the PTZ group; the compound group increased seizure latency more than Vit D3, agmatine, and melatonin groups and decreased the duration more than pre-treatment with Vit D3. We observed enhancement in superoxide dismutase (SOD) and catalase (CAT) activity in the treatment groups, while in the combination group, elevating CAT activity was comparable with Vit D3 and agmatine groups. The malondialdehyde level decreased in diazepam, agmatine, melatonin, and combination groups. Conclusion: The compound treatment was more efficient than each one alone in improving PTZinduced seizure, which may result from suppressing oxidative stress.

Arbidol, an antiviral drug, identified as a sodium channel blocker with anticonvulsant activity.

Sodium channel blockers (SCBs) have traditionally been utilized as anti-seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models. Patch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice. Arbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain-of-function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine-induced status epilepticus model. Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs.