Anticonvulsant Activity Research Articles

Synthesis, Characterization and Biological Evaluation of N [3-Chloro-2 (aryl)-4-oxoazitidin-1-y] pyridine-4-carboxamide

Isoniazid on addition with different aromatic aldehyde gives Schiff’s bases. The Schiff base so formed on treatment with chloroacetyl chloride and triethyl amine as a base catalyst in 1-4 Dioxan gives product 2a-2n.The synthesized compounds characterized by spectral analysis like IR, NMR & Mass and elemental analysis. The compounds were screened by anticonvulsant and antimycobacterial activity.

Synthesis and Pharmacological Evaluation of 3-alkyl/aryl–2- methylquinazolin-4-one Derivatives

Quinazolin-4-ones with 2, 3-disubstitution is reported to possess significant analgesic, anti-inflammatory and anticonvulsant activities. We have developed an efficient method for the synthesis of 3-substituted-2-methylquinazolin-4-one by the condensation reaction of Anthranilic acid, acetic anhydride with various amines. The synthesized compounds were evaluated for anxiolytic activity by Elevated plus Maze Test and Light and Dark Test. It is observed that the aliphatic and aromatic substitution at 3-position of 2-methylquinazolin-4-one gives potent anxiolytic activity. In particular, ENA showed highest anxiolytic activity in Elevated plus Maze Test and EMQ and AMQ showed highest anxiolytic activity in Light and dark test model

The Oxidative Stress in Epilepsy—Focus on Melatonin

Oxidative stress develops when there is an excess of oxidants leading to molecular and cellular damage. Seizure activity leads to oxidative stress and the resulting increased lipid peroxidation. Generally, antiseizure medications reduce oxidative stress, although the data on levetiracetam are ambiguous. Exogenous antioxidants (vitamin E, resveratrol, hesperidin, and curcumin) have been documented to exert an anticonvulsant effect in animal models of seizures and some recent clinical data point to curcumin as an affective adjuvant for the therapy of pediatric intractable epilepsy. Melatonin is an antioxidant with an ability to attenuate seizure activity induced by various convulsants in rodents. Its clinical effectiveness has been also confirmed in a number of clinical studies. Experimental studies point to a possibility that endogenous melatonin may possess proconvulsive activity. Moreover, some scarce clinical data seem to express this view; however, a limited number of patients were included. The anticonvulsant activity of exogenous melatonin may involve GABA-mediated inhibition, while endogenous melatonin may act as a proconvulsant due to a decrease in the brain dopaminergic transmission. Antioxidants, including melatonin, may be considered as adjuvants in the therapy of epilepsy and melatonin, in addition, in patients with epilepsy suffering from sleep disorders.

Synthesis and Biological Evaluation of Amino Acid and Peptide Conjugates of 5-Bromovaleric Acid.

Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against C. albicans and A. niger declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.

Anticonvulsant effects of pentoxifylline on seizures induced by pentylenetetrazole and maximal electroshock in male mice: The role of the nitrergic pathway

IntroductionEpilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear. This study focused at how the nitrergic system could be involved in PTPh’s anticonvulsant effects. MethodsSeizures were induced in male mice by intravenous pentylenetetrazole (PTZ) infusion (absence-like seizures), intraperitoneal PTZ injection, and maximal electroshock (generalized tonic-clonic seizures). PTPh was administered at various doses, alone or in combination with the NO precursor L-arginine, as well as non-selective (L-NAME) and selective NOS inhibitors (nNOS inhibitor 7-NI and iNOS inhibitor aminoguanidine). Seizure thresholds, latencies, incidence, and mortality were assessed. Moreover, in the next paradigm, using maximal electroshock model, we evaluate possible protective effects of PTPh against generalized tonic-clonic seizures and subsequent mortality. ResultsIn the intravenous PTZ model, PTPh (≥150 mg/kg) increased the seizure threshold, potentiated by L-arginine but reduced by L-NAME and 7-nitroindazole. In the intraperitoneal PTZ model, 150 mg/kg PTPh decreased tonic seizure frequency, which was mitigated by aminoguanidine. However, PTPh failed to prolong clonic seizure latency. In the maximal electroshock test, 100 mg/kg PTPh protected against tonic seizure incidence (reduced by aminoguanidine). Although PTPh could not reduce mortality, its combination with L-NAME or 7-nitroindazole increased mortality compared with the vehicle-treated group. ConclusionPTPh exerted anticonvulsant effects against absence-like and generalized tonic-clonic seizures, likely through modulation of the nitrergic system involving neuronal, endothelial, and inducible NOS isoform. These findings provide novel insights into the complex interplay between NO signaling and the anticonvulsant actions of PTPh, highlighting the potential therapeutic implications of targeting the NO pathway in epilepsy management.

Use of imidazo[1,5-a]quinoline scaffold as the pharmacophore in the design of bivalent ligands of central benzodiazepine receptors

The imidazo[1,5-a]quinoline scaffold of central benzodiazepine receptor (CBR) ligands was used as the pharmacophore in the design of bivalent ligands bearing spacers showing variable length and different physicochemical features. The newly designed compounds were synthesized along with the corresponding reference monovalent compounds bearing the corresponding spacers terminated with a tert-butoxycarbonyl group. The novel compounds were tested in binding assays with different CBR preparations such as the cerebral cortex from male CD-1 albino mice or the human recombinant α1β3γ2 and α2β3γ2 γ-aminobutyric acid type A receptors (GABAARs) stably expressed in mouse L(tk-) cells. The tested compounds showed IC50 values from the sub-micromolar up to the nanomolar range with very similar inhibition constants values for the two isoforms of GABAARs. The similarity in the affinity between the bivalent ligands and the corresponding monovalent ones appeared to rule out any bivalent interactions of these ligands with the two isoforms of GABAARs. Similarly, both series were able to inhibit the binding of radiolabeled flumazenil to GABAARs in cortical membranes of albino CD-1 mice, but most of the tested compounds showed biphasic inhibition curves, suggesting the existence of two well-distinct populations of binding sites. Finally, some CBR ligands selected from the bivalent ligands (i.e. 6a,c) and from the reference monovalent ligands (i.e. 7a) were then tested in vivo for their potential pharmacological effects, evaluating four classical benzodiazepine actions such as anticonvulsant, anxiolytic, locomotor, and anti-amnesic activities. All the tested compounds showed anticonvulsant and anxiolytic properties with neither muscle relaxant effect nor learning and memory impairments.

The Physiological and Pharmacological Roles of Melatonin and Pregabalin

Melatonin and pregabalin are two important compounds that are broadly used in the fields of physiological and medicinal sciences. Melatonin is a primary hormone mainly secreted by the pineal gland and plays an important role in regulating circadian rhythms, sleep-wake cycles, and neuroimmune processes. Its strong antioxidant anti-inflammatory and anti-apoptotic properties have protected it against a wide range of diseases, from cancer to neurological disorders. In this study, the synthesis of melatonin will be widely studied, mainly regarding its role in regulating circadian rhythms and sleep, and its possible therapeutic use in treating neurological diseases and inflammation-related disorders. Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid (GABA), with anticonvulsant, analgesic, and anxiolytic actions. Clinical practice has widely utilized it because studies indicate that it is useful in treating a variety of conditions: fibromyalgia, epilepsy, neuropathic pain, and generalized anxiety disorder. This article reviews aspects of the pharmacokinetics of pregabalin, its useful functions in pain treatment, and its impact on calcium channel regulation. The review also discusses indications of pregabalin in therapy, along with its possible side effects. This review article aims to consider the molecular processes underlying the activities of melatonin and pregabalin and their therapeutic potential for the management of sleep disorders, inflammation, and neurological diseases to future use of these compounds clinically.

DESIGN, SYNTHESIS, IN SILICO STUDIES, AND PHARMACOLOGICAL EVALUATION OF 5-ARYL-4-(CHLOROACETYLAMINO)-3-MERCAPTO-1,2,4-TRIAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

Objective: In this study, we reported the synthesis of a novel series of 5-aryl-4(chloroacetylamino)-3-mercapto-1, 2,4-triazoles. Methods: These compounds were synthesized to screen for anticonvulsant effects in a Maximal Electroshock Seizure (MES) model and a Subcutaneous Pentylenetetrazole (sc‐PTZ) seizure model in rats. Furthermore, molecular docking studies with gamma-aminobutyric acid and in silico ADME prediction were carried out to determine interactions of these compounds with Benzodiazepine (BZD) receptors and their similarity with standard drugs. The rotarod test was used to evaluate neurotoxicity. Results: 08 out of 40 compounds exhibited neurotoxicity at the maximum tested dose. Most of the compounds showed anti‐MES effects without any signs of neurological deficit. All the tested compounds significantly reduced seizures induced by PTZ compared to the control group. Carbamazepine and phenytoin were used as positive controls for anticonvulsant effects. Compounds 3d, 3h (a diphenylamine derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole), and 4a (a piperidinyl derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole) exhibited greater safety than phenytoin and carbamazepine in terms of neurotoxicity. The docking scores for the identified compounds 3d, 3h and 4a was 6.5133; 6.6558 and 5.6524, respectively. Nearly all the compounds (90%) demonstrated decreased locomotor activity. Conclusion: It is gratifying that the compounds with higher hydrophobicity showed better performance in the seizure models. Many triazole derivatives holding a suitable aryl or alkyl group gave a better anticonvulsant activity in their analogs.

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.

Exploring GABAA receptor modulation through integrated synthesis, bioactivity, and computational approach of 1,2,4-triazine derivatives

Epilepsy, a prevalent neurological disorder, is often treated with antiepileptic drugs (AEDs), which frequently suffer from toxicity, intolerance, and limited efficacy. Addressing these challenges, our study explores novel 1,2,4-triazine derivatives as potential AEDs. We designed, synthesized, and evaluated the anticonvulsant activity of derivatives HRS1-HRS42 in vivo, notably in the maximal electroshock (MES) and pentylenetetrazol (PTZ)-induced seizure models. Compounds HRS4 and HRS9 demonstrated significant anticonvulsive activity, with HRS9 exhibiting a higher effective dose (ED50 of 28.6 mg/kg) compared to traditional drugs like phenytoin (9.5 mg/kg) and carbamazepine (8.8 mg/kg). Additionally, these compounds displayed antioxidant properties through DPPH and FRAP assays. Importantly, compound HRS9 significantly altered neurotransmitter levels, increasing GABA and reducing glutamate in the brain tissue and cortex, which correlates with reduced seizure activity. Acute safety studies confirmed the safety of compound HRS9, with no significant pathological changes observed in histopathological analyses. Molecular interactions were analyzed using Field-based Gaussian 3D-QSAR, highlighting the importance of steric and hydrophobic effects in molecule design. Furthermore, docking studies demonstrated effective binding of compounds to alpha subunit sites within the GABAA receptor complex, corroborating the biochemical efficacy observed. Molecular dynamics in aqueous medium, and lipid bilayer environment and density functional theory further provided insights into the stability of ligand binding and electronic properties, critical for rational drug design. This comprehensive evaluation not only underscores the potential of 1,2,4-triazine derivatives in advancing the design of new molecules against epilepsy but also sets the stage for subsequent clinical studies to further explore their therapeutic viability.

Medicinal Attributes of Pyrazoline in Drug Discovery

: Pyrazoline are structurally versatile nitrogen-containing heterocycle that has gained more attention owing to its diversified pharmacological activities. This special scaffold serves as a fundamental component in a variety of bioactive chemicals, enabling the creation of new molecules with advantageous biological functions. The present review paper provides a summary of diversified pharmacological activities in particular, anticancer, antimalarial, antimicrobial, antifungal, antidepressant, anti-inflammatory, antinociceptive, antitubercular, anticonvulsant, anti-amoebic, antischistosomal, insecticidal, hypotensive, antiviral, antioxidant and anti-trypanosomal activity. This review also presents numerous simple synthetic techniques for the preparation of pyrazolines and also highlights the applicability of pyrazoline in drug discovery.

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

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

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.

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. Wh+e 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 APPswe/PS1dE9 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 (X2=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.

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.