Targeting Adipokines: A Promising Therapeutic Strategy for Epilepsy.

Epilepsy affects 65 million people globally and causes neurobehavioral, cognitive, and psychological defects. Although research on the disease is progressing and a wide range of treatments are available, approximately 30% of people have refractory epilepsy that cannot be managed with conventional medications. This underlines the importance of further understanding the condition and exploring cutting-edge targets for treatment. Adipokines are peptides secreted by adipocyte's white adipose tissue, involved in controlling food intake and metabolism. Their regulatory functions in the central nervous system (CNS) are multifaceted and identified in several physiology and pathologies. Adipokines play a role in oxidative stress and neuroinflammation which are associated with brain degeneration and connected neurological diseases. This review aims to highlight the potential impacts of leptin, adiponectin, apelin, vaspin, visfatin, and chimerin in the pathogenesis of epilepsy.

Clinical and Liver Biochemistry Phenotypes, and Outcome in 133 Patients with Anti-seizure Drug-Induced Liver Injury.

AIMS AND OBJECTIVE: Anti-seizure drugs that cause idiosyncratic drug-induced liver injury (DILI) are an important cause of morbidity and mortality in individuals exposed to these drugs. The clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity have not been thoroughly studied. We investigated the aforementioned characteristics in a large cohort of DILI registry patients. METHODS: Patients with anti-seizure DILI were studied from a large single-center DILI registry between 1998 and 2021. DILI was defined by international working group criteria with at least a probable relation with RUCAM. Immunoallergic features and organ-specific contribution to outcome were investigated. RESULTS: Anti-seizure drugs accounted for 133 patients (12.5%) among 1067 patients with idiosyncratic DILI. Compared to other agents, patients with anti-seizure DILI were younger (31 vs 41 years; p = 0.31), were more often females (52% vs 46%; p = 0.19) and had a lower frequency of jaundice (41% vs 59%, p = 0.001), MELD score (14.5 vs 16.5; p = 0.02) and mortality (9.8% vs 15.7%, p = 0.03). Anti-seizure DILI exhibited a greater frequency of hypersensitivity skin rashes (75% vs 22%, p < 0.001), including DRESS (51% vs 13%, p < 0.001) and SJS/TEN (19% vs1%, p < 0.001). A total of 18 different anti-seizure agents were responsible for DILI, largely contributed by carbamazepine (n = 36), phenytoin (n = 71), phenobarbitone (n = 8) and valproate (n = 14) which accounted for 89% of cases and 85% of 13 deaths. CONCLUSIONS: Anti-seizure DILI are caused predominantly by first generation drugs. Newer agents account for < 10% of cases. Hypersensitivity reaction is the most common phenotypic presentation. Both severity and mortality are lower with anti-seizure DILI.

A Comprehensive Review of Trigeminal Neuralgia.

PURPOSE OF REVIEW: Trigeminal neuralgia (TN) is characterized by recurrent attacks of lancinating facial pain in the dermatomal distribution of the trigeminal nerve. TN is rare, affecting 4 to 13 people per 100,000. RECENT FINDINGS: Although there remains a debate surrounding the pathogenesis of TN, neurovascular compromise is the most currently accepted theory. Minimal stimulation caused by light touch, talking, or chewing can lead to debilitating pain and incapacitation of the patient. Pain may occur sporadically, though is primarily unilateral in onset. The diagnosis is typically determined clinically. Treatment options include medications, surgery, and complementary approaches. Anti-epileptic and tricyclic antidepressant medications are first-line treatments. Surgical management of patients with TN may be indicated in those who have either failed medical treatment with at least three medications, suffer from intolerable side-effects, or have non-remitting symptoms. Surgical treatment is categorized as either destructive or non-destructive. Deep brain and motor cortex neuro-modulatory stimulation are off label emerging techniques which may offer relief to TN that is otherwise refractory to pharmacological management and surgery. Still, sufficient data has yet to be obtained and more studies are needed.

Evaluation of some neuropharmacological effects of Caladium bicolor aiton (araceae) leaf extracts in mice.

Caladium bicolor Aiton (Araceae) is used in ethnomedicine for the treatment of boils, wound ulcers and convulsion. This study investigated the effects of the leaf extracts on some neuropharmacological parameters. The leaves were collected, dried, powdered and then extracted by maceration in methanol to yield the whole extract (WE). Extraction was also done using n-hexane, ethyl acetate and methanol in a Soxhlet apparatus to obtain n-hexane (HE), ethyl acetate (EA) and methanol (ME) extracts. Preliminary phytochemical screening was done using the whole extract. Some neuropharmacological evaluations were carried out using standard methods. Phytochemical screening revealed the presence of carbohydrates, proteins, alkaloids and flavonoids. WE showed varying levels of protection against strychnine-induced convulsion. Each of HE, EA and ME increased latency (P < 0.01) to pentylenetetrazole-induced convulsion and offered varying levels of protection against maximal electroshock-induced seizure. Each of WE, HE and ME significantly increased the duration of stay on the open arm of the elevated plus maze. Both EA and ME at doses of 100 and 200 mg/kg, and HE at a dose of 400 mg/kg significantly reduced the duration of immobility in forced swim test. It is concluded that the leaf extracts possess anticonvulsant, anxiolytic and antidepressant properties.

Synthesis, molecular modelling, and preliminary anticonvulsant activity evaluation of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4] nonane-3,8-dione derivatives.

The synthesis, pharmacological evaluation and molecular modelling study of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives as potential anticonvulsant agents are described. The newly synthesized compounds were characterized by both analytical and spectral data. Alkylation of 1H-imidazole or substituted piperazine with 1-(2-naphthyl)-2-bromoethanone (2) gave naphthalen-2-yl 2-(1H-imidazol-1-yl) acetate (3) and naphthalen-2-yl 2-(substituted piperazin-1-yl) acetate (4-8). Moreover, condensation of naphthalen-2-yl 2-bromoacetate or 2-bromo-1-(naphthalen-2-yl) ethanone with hydrazine hydrate and acetylacetone resulted in the formation of the cyclic pyrazole products 9 and 13. Sonication of naphthalen-2-yl acetate (1) with 2-chloropyridine, 2-chloropyrimidine and 2-(chloromethyl) oxirane gave naphthalen-2-yl 2-(pyridin-2-yl) acetate (10), naphthalen-2-yl 2-(pyrimidin-2-yl) acetate (11) and naphthalen-2-yl-3-(oxiran-2-yl) propanoate (12) respectively. Cyclocondensation reaction of 2-iminothiazolidin-4-one (14) with thioglycolic acid, thiolactic acid and thiomalic acid gave 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives (15-17). The compounds were testedin vivofor the anticonvulsant activity by delaying strychnine-induced seizures. The diazaspirononane (17) and 1-(2-naphthyl)-2-bromoethanone (2) showed a high significant delay in the onset of convulsion and prolongation of survival time compared to phenobarbital. The molecular modelling study of anticonvulsant activity of synthesized compounds showed a CNS depressant activity via modulation of benzodiazepine allosteric site in GABA-A receptors.

The influence of ovariectomy on anti-convulsant effect of pioglitazone in mice.

The anti-convulsant effects of pioglitazone in male animals have been reported in previous studies. Both clinical and animal studies demonstrated that ovarian hormones can influence seizure activity. Pioglitazone has direct effects on ovaries and changes the level of gonadal hormones. In the current study, we examined the influence of ovariectomy on seizure threshold in pioglitazone-treated female mice. Two models of intravenous and intraperitoneal pentylenetetrazole-induced clonic seizures were used to analyze the effect of pioglitazone in sham and ovariectomized female mice. Different doses of pioglitazone were administered orally for 10 days in different groups. We demonstrated that chronic administration of pioglitazone (10 and 20mg/kg) increased clonic seizure threshold in intravenous pentylenetetrazole seizure model of female mice. We also indicated that chronic treatment with pioglitazone (10 and 20mg/kg) increased clonic seizure latency in intraperitoneal pentylenetetrazole seizure model in female mice, while the incidence of tonic seizure and death remained unchanged. Ovariectomy abolished anti-seizure effect of pioglitazone in both seizure models of intravenous and intraperitoneal pentylenetetrazole. In conclusion, pioglitazone exerts anti-convulsant effect in both seizure models of intravenous and intraperitoneal pentylenetetrazole possibly through gonadal hormones of ovary in female mice.

Crystal structures of 2-meth-oxy-isoindoline-1,3-dione, 1,3-dioxoisoindolin-2-yl methyl carbonate and 1,3-dioxo-2,3-di-hydro-1H-benzo[de]isoquinolin-2-yl methyl carbonate: three anti-convulsant compounds.

The title compounds, C9H7NO3, (1), C10H7NO5, (2), and C14H9NO5, (3), are three potentially anti-convulsant compounds. Compounds (1) and (2) are isoindoline derivatives and (3) is an iso-quinoline derivative. Compounds (2) and (3) crystallize with two independent mol-ecules (A and B) in their asymmetric units. In all three cases, the isoindoline and benzoiso-quinoline moieties are planar [r.m.s. deviations are 0.021 Šfor (1), 0.04 and 0.018 Šfor (2), and 0.033 and 0.041 Šfor (3)]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3)° for the N-O-Cmeth-yl group in (1), 71.01 (4) and 80.00 (4)° for the N-O-C(=O)O-Cmeth-yl groups in (2), and 75.62 (14) and 74.13 (4)° for the same groups in (3). In the crystal of (1), there are unusual inter-molecular C=O⋯C contacts of 2.794 (1) and 2.873 (1) Špresent in mol-ecules A and B, respectively. There are also C-H⋯O hydrogen bonds and π-π inter-actions [inter-centroid distance = 3.407 (3) Å] present, forming slabs lying parallel to (001). In the crystal of (2), the A and B mol-ecules are linked by C-H⋯O hydrogen bonds, forming slabs parallel to (10-1), which are in turn linked via a number of π-π inter-actions [the most significant centroid-centroid distances are 3.4202 (7) and 3.5445 (7) Å], forming a three-dimensional structure. In the crystal of (3), the A and B mol-ecules are linked via C-H⋯O hydrogen bonds, forming a three-dimensional structure, which is consolidated by π-π inter-actions [the most significant inter-centroid distances are 3.575 (3) and 3.578 (3) Å].

Crystal structure of 1,3-dimethyl-3-phenyl-pyrrolidine-2,5-dione: a clinically used anti-convulsant.

In the title compound, C12H13NO2, the five-membered ring has an envelope conformation; the disubstituted C atom lies out of the mean plane through the four other ring atoms (r.m.s. deviation = 0.0038 Å) by 0.1877 (18) Å. The plane of the phenyl substituent is practically perpendicular to that of the planar part of the five-membered ring, with a dihedral angle of 87.01 (5)°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming inversion dimers. The dimers are linked by further C-H⋯O hydrogen bonds, as well as carbon-yl-carbonyl attractive inter-actions [O⋯C = 3.2879 (19) Å], forming a three-dimensional framework structure.

Sodium Valproate-Induced Hyperammonemia: A Case Series in a Tertiary Care Hospital.

BACKGROUND: Sodium valproate (VPA) is an extensively used anti-convulsant, which is an effective drug for treatment of epilepsy in adults and children, as well as for conditions like migraine, bipolar disorder, mania, and trigeminal neuralgia. Sedation, vertigo, ataxia, dose-dependent tremors, headaches, and gastrointestinal side effects are the most often reported adverse effects associated with VPA. A potential life-threatening event reported with VPA is hyperammonemia (HA), which is defined as an increase in serum level of ammonia. Only 587 reported cases of HA were found in the VigiAccess database, representing a mere 0.6% of the 95,000 reported adverse events linked to VPA. Hence, this case series was conducted with emphasis on monitoring of increased serum ammonia levels with or without hepatic enzymes increase for patients who are on VPA. AIMS AND OBJECTIVES: To assess elevated serum ammonia levels following VPA administration, and to ascertain the percentage of individuals with hepatic enzymes increased who took VPA and subsequently had elevated serum ammonia levels. METHODS: This study was conducted at the adverse drug reaction (ADR) monitoring centre (AMC) of the Pharmacovigilance Programme of India (PvPI) and Department of Psychiatry, Christian Medical College and Hospital (CMC&H), Ludhiana. The study comprised of 12 patients who were exclusively on VPA and exhibited symptoms related to elevated serum ammonia. An informed consent form (ICF) was provided to the patient prior to taking their personal details. Laboratory investigations were done to establish the diagnosis and liver function tests (LFTs), chiefly ALT (alanine transferase) and AST (aspartate aminotransferase) were also performed. It is a descriptive study which was for a time period of six months.  Results: This study includes 12 patients who had HA confirmed by laboratory investigation. Out of these 12 patients, two patients (17%) had a corresponding increase in LFT. The average as of the patients was 53.08 years and average serum ammonia levels were 219.15. None of the patients who presented with HA progressed to hyperammonemic encephalopathy (HAE). CONCLUSION:  This case series on valproate-induced HA should be of interest to psychiatrists, physicians, internists, family medicine physicians, hospitalists, and surgeons who will have patients on VPA. Delay in recognition of HA can result in the development of potentially life-threatening complications. Rapid diagnosis and management will help in reducing the number of cases which progress to encephalopathy which is highly fatal.

Rationalising the dose threshold for severe carbamazepine toxicity: a retrospective series.

INTRODUCTION: Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. METHODS: This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). RESULTS: There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71-151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). DISCUSSION: Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. CONCLUSION: Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series.

Design, synthesis, molecular docking and pharmacological evaluation of some thiadiazole based nipecotic acid derivatives as a potential anticonvulsant and antidepressant agents.

In our continuous effort to develop novel antiepileptic drug, a new series of nipecotic acid derivatives having1,3,4-thiadiazole nucleus were designed and synthesized. This study aims to improve the lipophilicity of nipecotic acid by attaching some lipophilic anchors like thiadiazole and substituted aryl acid derivatives. In our previous study, we noticed that the N-substituted oxadiazole derivative of nipecotic acid exhibited significant antiepileptic activity in the rodent model. The synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, Mass, and elemental analysis. The anticonvulsant activity was evaluated by using the maximal electroshock-induced seizure model in rats (MES) and the subcutaneous pentylenetetrazol (scPTZ) test in mice. None of the compounds were found to be active in the MES model whereas compounds (TN2, TN9, TN12, TN13, and TN15) produced significant protection against the scPTZ-induced seizures model. The compounds showing antiepileptic activity were additionally evaluated for antidepressant activity by using the forced swim test, 5-hydroxytryptophan (5-HTP)-induced head twitch test, and learned helplessness test. All the molecules that showed anticonvulsant activity (TN2, TN9, TN12, TN13, and TN15), also exerted significant antidepressant effects in the animal models. The selected compounds were subjected to different toxicity studies. Compounds were found to have no neurotoxicity in the rota-rod test and devoid of hepatic and renal toxicity in 30 days repeated oral toxicity test. Further, a homology model was developed to perform the in-silico molecular docking and dynamics studies which revealed the similar binding of compound TN9 within the active binding pocket and were found to be the most potent anti-epileptic agent. The market expectation for newly developed antiepileptic thiadiazole-based nipecotic acid derivatives is significant, driven by their potential to offer improved therapeutic outcomes and reduced side effects, addressing a critical need in epilepsy treatment. These innovative compounds hold promise for meeting the demand for more effective and safer antiepileptic medications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03897-1.

The bidirectional role of music effect in epilepsy: Friend or foe?

Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti-seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long-term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti-convulsant effect, some particular music would cause seizures inversely, indicating the pro-convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti-convulsant and pro-convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. PLAIN LANGUAGE SUMMARY: Epilepsy is an extremely severe neurological disorder. Although anti-seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro-convulsive, or anti-convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

Novel 1,4 benzothiazine 3-one derivatives as anticonvulsant agents: Design, synthesis, biological evaluation and computational studies.

In this study, two series of novel 1,4-benzothiazine-3-one derivatives with alkyl substitution (series 1: 4a-4f) and aryl substitution (series 2: 4g-4l) were designed and synthesized based on the chemical scaffolds of perampanel, hydantoins, progabide and etifoxine as anti-convulsant agents. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1H NMR and 13C NMR spectroscopy. Anti-convulsant effect of the compounds was examined through intraperitoneal pentylenetetrazol (i.p. PTZ) induced epilepsy mouse models. Compound 4h (4-(4-bromo-benzyl)- 4 H-benzo[b] [1,4] thiazin-3(4 H)-one) demonstrated a promising activity toward chemically-induced seizure experiment. Molecular dynamics simulation on GABA-Aergic receptors as a plausible mechanism were also done to achieve the binding and orientation of compounds in the active site of the target to evaluate the results of docking and experimental studies. The computational results were confirmed the biological activity. DFT study of 4c and 4h was performed on B3LYP/6-311 G** level of theory. Reactivity descriptors such as HOMO, LUMO, electron affinity, ionization potential, chemical potential, hardness and softness were studied in detail and show that 4h has higher activity than 4c. Also, the frequency calculations were performed on the same level of theory and the results are in line with experimental data. Moreover, in silico ADMET properties were done to establish a relationship between the physiochemical data of the designed compounds and their in-vivo activity. Appropriate plasma protein binding and high blood-brain barrier penetration are the main features of desired in-vivo performance.

Anti-Convulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.-Ham. Ex D.Don (Lamiaceae) in Mice.

Background: The leaves of Ajuga integrifolia Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. Methods: The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined. Results: Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (p<0.01) in the PTZ test compared to controls. It also significantly reduced (p<0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols. Conclusion: This study indicated that the plant A. integrifolia has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.

Synthesis and crystal structure of topiramate azido-sulfate at 90†K and 298†K.

The low (90 K) and room (298 K) temperature crystal structures of topiramate azido-sulfate [systematic name 2,3:4,5-bis-O-(1-methyl-ethyl-idene)-ß-d-fructo-pyran-ose azido-sulfate], C12H19N3O8S, an inter-mediate in the synthesis of the anti-convulsant drug topiramate, are described. Topiramate azido-sulfate (I) finds use as a reference impurity standard for topiramate. A modified synthesis and some spectroscopic details are also presented.

Cattle Bile Arisaema Aqueous Extracts Protect Against Febrile Seizures in Rats Through Regulating Neurotransmitters and Suppressing Neuroinflammation.

Cattle bile Arisaema (CBA) is a traditional medicine used for the treatment of febrile seizures (FS) for thousands of years in China. However, its application is greatly limited due to cost reasons, and pig bile Arisaema (PBA) is the main commercial product instead. Additionally, the underlying mechanism of CBA for the treatment of FS still remains unknown. In this study, we investigated the anti-convulsant effect and potential mechanism of the CBA aqueous extract for the first time through a hot-water bath-induced FS rat model. Our results showed that pre-treatment with CBA dramatically lowered the incidence rate and generation times and prolonged the latency of FS. In addition, CBA effectively ameliorated neuronal damage and regulated neurotransmitter disorder induced by FS in the rat hippocampus. The enzyme-linked immunosorbent assay, western blotting, immunohistochemical, and qRT-PCR results exhibited that CBA suppressed the expression of GFAP, TLR4, NF-κB, HMGB1, NLRP3, TNF-α, IL-1ß, and IL-6 and consequently inhibited the neuroinflammation induced by FS. Interestingly, although the CBA and PBA aqueous extracts possessed the same trend on the changes caused by FS, the improvement of FS by CBA is markedly better than that by PBA. These findings indicate that CBA exerts a protective effect on febrile seizures through regulating neurotransmitter disorder and suppressing neuroinflammation.

Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808.

The expression of genes altered in epilepsy remains incomplete, particularly in the hippocampus, which exhibits exquisite vulnerability to epilepsy. Q808 is an innovation chemical compound that has potent anti-convulsant effect. Exploring its mechanism can not only explore the pathogenesis of epilepsy but also provide a theoretical basis for its clinical application. The present study aimed to use RNA sequencing (RNA-seq) to reveal the gene transcriptomic profile of chronic pentylenetetrazole (PTZ)-kindled seizure rats and the difference of the PTZ model rat before and after treatment with Q808. Quantitative real-time PCR (qRT-PCR) was performed to validate the RNA-seq results. The protein level was estimated with Western blot. Hippocampal transcriptomic analysis showed that 289 differentially expressed genes (DEGs) were confirmed in the PTZ-kindled seizure group compared with the vehicle control. Gene cluster analysis identified most of the DEGs linked to neuronal apoptosis, neurogenesis, neuronal projections, and neurotransmitter regulation. After analysis across the three groups, 23 hub genes and 21 pathways were identified, and qRT-PCR analysis confirmed that most of the mRNA levels of hub genes were consistent with the RNA-seq results. Q808 treatment increased the level of ACE, a GABA-related protein. Our analysis showed the comprehensive compendium of genes and pathways differentially expressed for PTZ-kindled seizure rats and upon Q808 treatment in PTZ-kindled seizure, which may provide a theoretical basis to explore the mechanism and unique efficacy of Q808 and the pathophysiology of epilepsy in the future.

Oxcarbazepine-Induced Hyponatremia: A Case Report and Comprehensive Literature Review.

Oxcarbazepine is a well-known and effective anti-convulsant used for patients with underlying seizure disorder. It is a structural analog of carbamazepine; however, it follows a different metabolic pathway in which it is converted to a different active metabolite. Side effects associated with this medication are vast; however, in this report, we will hone in on the renal adverse effects, e.g., syndrome of inappropriate anti-diuretic hormone secretion (SiADH). SiADH is a condition in which the body is making too much anti-diuretic hormone, which, in turn, results in "too much" water absorption, causing hyponatremia with neurologic sequelae. Our patient is a 31-year-old gentleman with a history of depression, anxiety, bipolar disorder, and previous suicide attempts who presented to the emergency department following oxcarbazepine overdose and was subsequently found to be hyponatremic secondary to having SiADH.

1,3,4-Thiadiazole Scaffold: As Anti-Epileptic Agents.

A wide range of biological activities is exhibited by 1,3,4-thiadiazole moiety such as antidiabetic, anticancer, anti-inflammatory, anticonvulsant, antiviral, antihypertensive, and antimicrobial. To date, drugs such as butazolamide, and acetazolamide. Several modifications have been done in the 1,3,4-thiadiazole moiety which showed good potency as anticonvulsant agents which are highly effective and have less toxicity. After in-depth literature survey in this review, we have compiled various derivatives of 1,3,4-thiadiazole scaffold as anticonvulsant agents.

Evaluation of sodium valproate low dose efficacy in radicular pain management and it's relation with pharmacokinetics parameters.

BACKGROUND: Radiculopathy due to lumbar or cervical disc disease is the most common chronic neuropathic pain in adults. The aim of present study was evaluation of low dose of sodium valproate (VPA) on radicular pain and determining VPA pharmacokinetics. MATERIALS AND METHODS: In this double blind randomized placebo control clinical study, 80 patients with established lumbar or cervical radicular pain, have been randomly allocated into two study groups: 40 have received sodium valproate 200 mg/day and Celecoxib 100 mg/day and acetaminophen 500 mg PRN as rescue medication, and second group has received placebo, Celecoxib and acetaminophen. Quantitative assessment of pain was done by visual analogue scale (VAS) prior to perform the intervention and after ten days (treatment duration). Blood sample has been taken for determining mean through concentration after five half-lives. Evaluation of plasma concentration of VPA and that of efficacy on pain score relationship by comparing VAS before and after the therapy was done. RESULTS: Group A and B have demonstrated significant alleviation in mean VAS score; -21.97 ± 25.41, -14.39 ± 23.03 respectively (P < 0.001). The mean plasma concentration of VPA in group A was: 26.9 ± 13.5 mg/L. Moreover, no significant correlation was seen between pain score with age, gender, and weight (p > 0.05). CONCLUSION: Low dose of sodium valproate especially together with NSAIDs demonstrated good efficacy in lumbar and cervical radicular pain management.