Induced Seizure Model Research Articles

Pharmacological Screening of Rhizome of Curcuma amada roxb. in Rodent models

This is the first report to screen scientifically an anticonvulsant effect of hydroalcoholic extract of Curcuma amada in different animal models. The results revealed that treatment with hydroalcoholic extract of Curcuma amada protected against MES and PTZ-induced convulsions and mortality, and these effects were comparable with standard anticonvulsant agents. In order to evaluate the therapeutic value of hydroalcoholic extract as anticonvulsant, we tested its influence in different animal models viz., PTZ and MES-induced seizures in Swiss albino mice. In MES induced seizure model, hydroalcoholic extract of Curcuma amada dose dependently decreased duration of hind limb extension that was comparable to that of diazepam. The mechanism by which hydroalcoholic extract of Curcuma amada produced anticonvulsant effect against MES-induced seizures is not known. We also tested the effects of hydroalcoholic extract of Curcuma amada against convulsions induced by PTZ, an agent widely reported to induce convulsion by inhibition and/or attenuation of GABA-ergic neurotransmission.

Evaluation of sodium valproate loaded nanoparticles in acute and chronic pentylenetetrazole induced seizure models

Background and purposeEfficacy of sodium valproate in epilepsy is limited by its poor blood brain barrier penetration and side effects. Nanoparticles may offer a better drug delivery system to overcome these limitations. This study evaluated the efficacy of sodium valproate encapsulated in nanoparticles in pentylenetetrazole (PTZ) induced acute and kindling models of seizures in male Wistar rats. MethodsPoly lactic-co-glycolic acid (PLGA) based, polysorbate 80 stabilized sodium valproate loaded nanoparticles (nano sodium valproate) and rhodamine loaded nanoparticles (RLN) were formulated by double emulsion- solvent evaporation method and characterized for their size, shape, zeta potential and drug loading percentage. RLN was used to demonstrate blood brain barrier (BBB) permeability of nanoparticles. Serum drug levels were estimated using high performance liquid chromatography. The efficacy of standard sodium valproate (300 mg/kg) and nano sodium valproate (∼300, ∼150 and ∼75 mg/kg of sodium valproate) were evaluated in experimental animal models of seizures along with their effects on behavioral and oxidative stress parameters. Drugs were administered 60 min before PTZ in acute model. In the kindling model, drugs were administered every day while PTZ was administered on alternate days 60 min after drug administration. All the study drugs/compounds were administered intraperitoneally. ResultsRLN were observed to be clustered in cortex which implied that the nanoparticles crossed BBB. Both standard sodium valproate and nano sodium valproate reached therapeutic serum level at 15 min and 1 h, but were undetectable in serum at 24 h. In acute PTZ (60 mg/kg) model, nano sodium valproate (∼300 mg/kg of sodium valproate) and standard sodium valproate showed protection against seizures till 6 h and 4 h, respectively. There were significant behavioral impairment and oxidative stress with standard sodium valproate in acute model as compared to nano sodium valproate at 6 h. In kindling model, induced with PTZ (30 mg/kg, every alternate day for 42 days), complete protection from seizures was observed with nano sodium valproate (∼150 mg/kg and ∼75 mg/kg of sodium valproate) and standard sodium valproate (300 mg/kg). Similarly, significant protection from behavioral impairment and oxidative stress was observed with standard sodium valproate and nano sodium valproate as compared to PTZ. ConclusionWhen compared to conventional therapy, nano sodium valproate showed protection from seizures at reduced doses and for a longer duration in animal models of epilepsy. This study suggests the potential of nano sodium valproate in the treatment of epilepsy.

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)-induced seizures model in rat, the motor response, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The motor response of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis percentage, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing the motor response and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

Proconvulsant effects of sildenafil citrate on pilocarpine-induced seizures: Involvement of cholinergic, nitrergic and pro-oxidant mechanisms

Sildenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Proconvulsant effect is a serious adverse event associated with sildenafil use. Here, we investigated the possible proconvulsant effects of sildenafil in pilocarpine (PILO)-induced seizures model, which mimics some aspects of temporal lobe epilepsy. We also evaluated sildenafil’s effects on hippocampal markers related to PILO-induced seizure, for instance, acetylcholinesterase (AChE) activity, oxidative stress and nitric oxide (NO) markers, namely nitrite, inducible NO synthase (iNOS) and neuronal NOS (nNOS). The influences of muscarinic receptors blockade on sildenafil proconvulsant effects and brain nitrite levels were also evaluated. Male mice were submitted to single or repeated (7 days) sildenafil administration (2.5, 5, 10 and 20 mg/kg). Thirty minutes later, PILO was injected and mice were further evaluated for 1 h for seizure activity. Sildenafil induced a dose- and time-progressive proconvulsant effect in PILO-induced seizures. Sildenafil also potentiated the inhibitory effect of PILO in AChE activity and induced a further increase in nitrite levels and pro-oxidative markers, mainly in the hippocampus. Repeated sildenafil treatment also increased the hippocampal expression of iNOS and nNOS isoforms, while the blockade of muscarinic receptors attenuated both sildenafil-induced proconvulsant effect and brain nitrite changes. Our data firstly demonstrated the proconvulsant effect of sildenafil in PILO-model of seizures. This effect seems to be related to an increased cholinergic-nitrergic tone and pro-oxidative brain changes. Also, our findings advert to caution in using sildenafil for patients suffering from neurological conditions that reduces seizure threshold, such as epilepsy.

Design, Synthesis, Anticonvulsant Activity, Preclinical Study and Pharmacokinetic Performance of N-{[3-(4-chlorophenyl)-4-oxo-3, 4-dihydroquinazolin- 2-yl] methyl}, 2-[(2-isopropyl-5-methyl) 1-cyclo Hexylidene] Hydrazinecarboxamide.

N-{[3-(4-chlorophenyl)-4-oxo-3, 4-dihydroquinazolin-2-yl] methyl}, 2-[(2- isopropyl-5-methyl) 1-cyclohexylidene] hydrazinecarboxamide QS11 was designed by computational study. It possessed essential pharmacophoric features for anticonvulsant activity and showed good docking with iGluRs (Kainate) glutamate receptor. QSAR and ADMET screening results suggested that QS11 would possess good potency for anticonvulsant activity. QS11 was synthesised and evaluated for its anticonvulsant activity and neurotoxicity. QS11 showed protection in strychnine, thiosemicarbazide, 4-aminopyridine and scPTZ induced seizure models and MES seizure model. QS11 showed higher ED50, TD50 and PI values as compared to the standard drugs in both MES and scPTZ screen. A high safety profile (HD50/ED50 values) was noted and hypnosis, analgesia, and anaesthesia were only observed at higher doses. No considerable increase or decrease in the concentration of liver enzymes was observed. Optimized QS11 was subjected to preclinical (in-vivo) studies and the pharmacokinetic performance of the sample was investigated. The result revealed that the pharmacokinetic performance of QS11 achieved maximum plasma concentrations (Cmax) of 0.315 ± 0.011 µg/mL at Tmax of 2.0 ± 0.13 h, area under the curve (AUC0-∞) value 4.591 ± 0.163 µg/ml x h, elimination half-life (T1/2) 6.28 ± 0.71 h and elimination rate constant was found 0.110 ± 0.013 h-1 . Above evidences indicate that QS11 could serve as a lead for development of new antiepileptic drugs.

ANTICONVULSANT ACTIVITY OF RAUWOLFIA TETRAPHYLLA LEAF EXTRACT IN SWISS ALBINO MICE

Objective: Rauvolfia tetraphylla is a plant potentially applicable in Ayurvedic and Unani System of Medicine for the treatment of various diseases. However, the anticonvulsant activity of this plant has not been reported and studied. Therefore, the ethanolic extract of leaf from the plant R. tetraphylla is used to evaluate anticonvulsant activity.&#x0D; Methods: Anticonvulsant activity was screened using maximal electroshock seizure (MES) model and pentylenetetrazole (PTZ)-induced seizure model in Swiss albino mice. The ethanolic extract was also evaluated for rutin and gallic acid content by high-performance thin-layer chromatography studies.&#x0D; Results: Rutin and gallic acid contents were found as 15.60% and 7.81%, respectively. Ethanolic leaf extract (100–800 mg/kg) significantly reduced the duration of seizures which was induced by MES. The same doses also protected animals from PTZ-induced tonic seizures.&#x0D; Conclusion: The study demonstrates that R. tetraphylla plant leaves have significant anticonvulsant activity.

Up-regulation of antioxidative proteins TRX1, TXNL1 and TXNRD1 in the cortex of PTZ kindling seizure model mice.

Oxidative stress has been considered as one of pathogenesis of brain damage led by epilepsy. Reducing oxidative stress can ameliorate brain damage during seizures. However, expression levels of important antioxidative enzymes such as thioredoxin-1 (TRX1), thioredoxin-like 1 protein (TXNL1) and thioredoxin reductase 1 (TXNRD1) during seizures have not been investigated. In this study, we examined protein and mRNA expression levels of TRX1, TXNL1 and TXNRD1 in different brain regions in PTZ induced seizure model mice. We found that protein expression levels of TRX1, TXNL1 and TXNRD1 are simultaneously up-regulated by 2- or 3-fold in the cortex of both acute and chronic seizure model mice. But there is no unified expression pattern change of these enzymes in the hippocampus, cerebellum and diencephalon in the seizure model mice. Less extent up-regulation of mRNA expression of these enzymes were also observed in the cortex of seizure mice. These data suggest that antioxidative enzymes may provide a protective effect against oxidative stress in the cortex during seizures.

A novel oxazolidinone derivative PH192 demonstrates anticonvulsant activity in vivo in rats and mice

The pharmacotherapeutic management of seizure disorders with currently available medications is not optimal due to side effects and failure of some patients to respond to all available medications. As such there is the need to develop new antiseizure drugs by looking at new chemical classes of compounds. We recently screened, in vitro, a new class of compounds, the oxazolidinones, for actions in the brain that may indicate potential for antiseizure activity. A few compounds were identified with such a potential. Here we tested whether one of these lead compounds, PH192, will exhibit in vivo antiseizure activity using chemically- and electrically- induced seizures models in mice and rats. Out of 5 compounds tested, all of them had minimal neurotoxicological effects in mice, with PH192 being the best, with comparable efficacy (ED50) and toxicity (TD50) to only levetiracetam. Intraperitoneal (IP) pretreatment with PH192 produced a dose-dependent protection of mice from seizures induced using the 6 Hz stimulation protocol with an estimated ED50 of 34.5 mg/kg in mice and about 90 mg/kg in rats and a neurotoxic dose >500 mg/kg in mice, yielding a calculated neuro (protective) index of >14.7. When pretreated with 100 mg/kg PH192 for 30 min, about 75% of mice were protected from 6 Hz-induced seizures. When rats were pretreated for 30 min with PH192, 66.6% of rats were protected from seizures induced using the 6 Hz stimulation protocol while 83.3% were protected using the maximal electroshock (MES) stimulation protocol. Pentylenetetrazole (PTZ) injection at 50, and 100 mg/kg produced stage 5 seizures in all rats. Thirty minutes IP pretreatment of rats with 100 mg/kg PH192 protected 80% of rats from the PTZ-induced seizures, a level of protection similar to that obtained with a reference antiepileptic drug (AED) phenytoin (40 mg/kg), that is used clinically for the treatment of various seizure disorders. The results of these studies indicate that PH192 protects against both chemically- and electrically-induced seizures with little central nervous system side effects. This suggests that the oxazolidinone pharmacophore has potential for discovering new antiepileptic drugs with possibly minimal central side effects.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

Evaluation of Anticonvulsant Activity and Toxicity Screening of Semicarbazones Derived from Quinazolinone Scaffold

Background: Epilepsy is one of the most prevalent noncommunicable neurological conditions. More than 10 million people in India are afflicted with epilepsy. Treatment available has many detrimental side effects. Up to one-third of epilepsy patients remain resistance to optimum drug treatment. These facts triggered the further scope and search for newer more effective and less toxic anticonvulsants. Methods: Quinazolinone semicarbazone derivatives showing protection in chemoconvulsant induced seizure models (as reported in our previous study) were further screened in MES and scPTZ induced seizure models. Neurotoxicity was determined; quantification of anticonvulsant activity and toxicity was also done. Finally compounds were screened by liver functional test to ascertain the possible hepatotoxicity in the active compounds. Results: Compounds N-1- (menthone) -N- [3-(4-(substituted)-phenyl) -4-oxo- 3,4-dihydroquinazolin- 2-yl] methyl semicarbazone (3A-d-4, 3B-d-4 and 3C-d-4) showed significant protection in both MES and scPTZ induced seizure model with no neurotoxicity at the given dose. In MES test, compounds showed an ED50 close to that of phenytoin and carbamazepine. They also showed Protective Index (PI) higher as compared to phenytoin and carbamazepine. A high safety profile (HD50/ED50 values) was noted and hypnosis, analgesia, and anesthesia were only observed at higher doses. Conclusion: Compounds showed no significant increase or decrease in the concentration of alkaline phosphatase, Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), albumin and bilirubin.

Anticonvulsant and neuroprotective effects of methanolic extract of Cinnamomum camphora leaves in rat brain

The aim of this study was to investigate the anticonvulsant and neuroprotective effects of methanolic extract of Cinnamomum camphora leaves (MECC) in albino wistar rats against maximal electroshock seizure (MES) and seizures induced by pentylenetetrazol (PTZ) models. Acetylcholinesterase (AChE) activity and oxidative stress parameters like malondialdehyde (MDA) and reduced glutathione (GSH) were estimated in the brains after completion of the anticonvulsant studies. MECC (50 and 100 mg/kg b.w., p.o.) exhibited anticonvulsant activity as indicated by significant (P < 0.05, P < 0.01) reduction in the duration of hind limb tonic extensor phase in MES induced seizure model and significantly (P < 0.05, P < 0.01) increased the time of onset of clonic convulsion, decreased the duration of seizures, increased the % protection and decreased the percent mortality in a dose dependent manner. MECC (50 and 100 mg/kg b.w., p.o.) exhibited neuroprotective activity as indicated by significant reduction in MDA levels, AChE activity and increased GSH level also in a dose dependent manner. These results indicate that MECC may exert anticonvulsant and neuroprotective effects which may be attributed to the increase in the level of GABA, inhibition of AChE and inflammation and antioxidant activity in the brain.

Inhibition of Acid Sensing Ion Channel 3 Aggravates Seizures by Regulating NMDAR Function.

The existing data about whether acid sensing ion channels (ASICs) are proconvulsant or anticonvulsant are controversial. Particularly, acid sensing ion channel 3 (ASIC3) is the most sensitive to extracellular pH and has the characteristic ability to generate a biphasic current, but few studies have focused on the role of ASIC3 in seizure. Here we found ASIC3 expression was increased in the hippocampus of pilocarpine induced seizure rats, as well as in hippocampal neuronal cultures undergoing epileptiform discharge elicited by Mg2+-free media. Furthermore, ASIC3 blockade by the selective inhibitor APETx2 shortened seizure onset latency and increased seizure severity compared with the control in the pilocarpine induced seizure model. Incubation with APETx2 enhanced the excitability of primary cultured hippocampal neurons in Mg2+-free media. Notably, the aggravated seizure was associated with upregulation of the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs), increased NMDAR mediated excitatory neurotransmission and subsequent activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cAMP-response element binding protein (CREB) signaling pathway. Moreover, co-immunoprecipitation confirmed the interaction between ASIC3 and NMDAR subunits, and NMDARs blockade prevented the aggravated seizure caused by ASIC3 inhibition. Taken together, our findings suggest that ASIC3 inhibition aggravates seizure and potentiates seizure induced hyperexcitability at least partly by the NMDAR/CaMKII/CREB signaling pathway, which implies that ASIC3 agonists may be a promising approach for seizure treatment.

Study of anticonvulsant activity of acetazolamide on albino rats and its influence on anticonvulsant activity of sodium valproate

Background: Epilepsy is a common neurological disorder. 30-40% of patients will continue to have seizures despite the use of antiepileptic drugs either alone or in combination. The present study is undertaken to evaluate the anticonvulsant activity of Acetazolamide (ACZ) in albino rats and its influence on anticonvulsant activity of sodium valproate.Methods: Albino rats (150-200gms) of male sex were randomly selected, from central animal facility, MMCRI, Mysore. They were divided into 6groups (per model) of 6 rats each, control group-normal saline 0.5ml, standard group-sodium valproate (300mg/kg), dose 1-ACZ (8.75mg/kg), dose 2-ACZ (17.5mg/kg) and dose 3-ACZ (35mg/kg), dose 4-ACZ (8.75mg/kg) with sodium valproate (150mg/kg). The anti-convulsant activity was screened using MES model and PTZ model.Results: Results were analysed by ANOVA followed by post hoc Fisher’s LSD test. The ACZ has shown anticonvulsant activity at the dose of 17.5mg/kg and 35mg/kg body weight and combination of ACZ 8.75mg/kg with sodium valproate 150mg/kg both in MES model and PTZ model. The anticonvulsant activity of ACZ was less when compared to Sodium Valproate in both MES model and PTZ model. The anticonvulsant activity of combination, ACZ 8.75mg/kg with Sodium valproate 150mg/kg was comparable and more significant when compared to standard drug alone in MES model and PTZ model.Conclusions: The ACZ has shown anticonvulsant activity in MES model and PTZ induced seizure model of epilepsy. This study has shown that ACZ potentiated the effect of sodium valproate and can be used as add on drug with sodium valproate in epilepsy.

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p &lt;0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

Evaluation of antiepileptic activity of trachyspermum ammi (ajwain oil) alone and as an adjuvant to diazepam in swiss albino mice

Background: Epilepsy is defined as a group of chronic neurological disorders characterized by recurrent and unprovoked seizures. Taking into account high prevalence of epilepsy and the adverse effects of the current antiepileptic agents which leads to noncompliance, more attempts should be made to re-explore the natural sources for new drug discoveries.Methods: The antiepileptic activity of Ajwain oil alone and as adjuvant to diazepam in swiss albino mice was evaluated using Maximum Electro Shock (MES) and Pentylenetetrazole (PTZ) induced seizure model. A total of forty eight (N=48) swiss albino mice weighing 20-30g of either sex were used in the study. Animals were divided into 2 sets of 24 animals each, which were further divided into 4 groups of 6 animals each. In either set, control received - 2% Tween 80 (10mg/kg); standard- Diazepam (2mg/kg); Test drug- Ajwain oil (75mg/kg) and Adjuvant group- Ajwain oil (75mg/kg) + Diazepam (2mg/kg). All the drugs were given intraperitoneally 30min before inducing seizures.Results: One way ANOVA was used to compare the means of all the groups followed by post Hoc Tukey’s test for statistical evaluation. In MES model, test drug showed statistically significant antiepileptic activity compared to control, however the results were comparable to standard. In PTZ, adjuvant therapy showed significant activity compared to standard, with a p value &lt;0.001.Conclusions: Therefore, authors conclude that Ajwain oil has significant anti-epileptic activity.

Synthesis, Molecular Docking and Evaluation of 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1, 3] oxazin/thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one Derivatives for their Anticonvulsant Activity.

According to the WHO, around 50 million people worldwide are suffering from epilepsy. It is due to the repeated occurring of seizures. These seizures are caused by sudden which may vary from a brief lapse of attention or muscle jerks, to severe and prolonged convulsions. The aim of the present work was to synthesize 2-phenyl substituted quinazolinone derivatives and to evaluate them for anticonvulsant and neurotoxic activity. A series of novel 3-{4-[2-amino-4-(substitutedphenyl)-2H-[1.3] oxazin/thiazin-6-yl} 2- phenyl-3H-quinazolin-4-one derivatives were synthesized and evaluated for their anticonvulsant activity. The structures of the compound have been confirmed by spectral analysis. The molecular docking was performed for all the synthesized compounds to assess their binding mode to Gamma- aminobutyric acid type A (GABAA) receptor in order to rationalize their anticonvulsant activities in a qualitative way. Anticonvulsant activities of compounds were screened by using (Maximal electroshock) MES induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in Wistar rats of either sex. None of the compounds demonstrated any sign of neurotoxicity. Compounds 3-{4-[2-amino-4-(4-nitro-phenyl)-2H-[1, 3] oxazin-6-yl} 2-phenyl-3H-quinazolin- 4-one (5a) have shown significant activity against tonic seizure by the MES model and 3-{4-[2-amino- 4-(4-nitro-phenyl)-2H-[1, 3] thiazin-6-yl} 2-phenyl-3H-quinazolin-4-one (5d) against clonic seizure by scPTZ induced seizure model. All the newly synthesized compounds had significant anticonvulsant activity. The same two compounds 5a and 5d showed promising activity, while the other compounds have moderate activity. The proposed work is to effort towards the development and identification of novel molecules as anticonvulsant agents by the synthesis of some novel quinazolinone derivatives with improved biological activity.

ANTICONVULSANT EFFECT OF AQUEOUS EXTRACT OF AERIAL ROOT OF FICUS RELIGIOSA IN ANIMAL MODELS

Ficus religiosa commonly found tree in Indian sub-continent has numerous neuro-pharmacological effects including epilepsy in traditional medicine. Therefore, anticonvulsant effect of aqueous aerial root extract of F. religiosa at oral doses 25, 50 and 100 mg/kg was studied using Maximum electroshock (MES) and Pentylenetetrazole (PTZ) induced seizure models in mice. F. religiosa showed anticonvulsant effect dose dependently in MES & PTZ test. In MES model F. religiosa 100mg/kg significantly (p < 0.05) lowered duration of Tonic hind limb extension. In PTZ model, all three doses of F. religiosa significantly (p < 0.05)  increased latency to convulsion. These findings thus provide scientific evidence in support of the folkloric use of this plant in the management of epilepsy. Keywords: Anticonvulsant, Ficus religiosa, Maximum electroshock, Pentylenetetrazole, Root

The Effects of Aqueous Extract of Apium Graveolens on Brain Tissues Oxidative Damage in Pentylenetetrazole-induced Seizures Model in Rat

Introduction: An important role for oxidative stress both as a consequence and as a cause of epileptic seizures has been suggested. Regarding the antioxidant and central nervous system depressant effects of Apium graveolens, the effects of aqueous extract of the plant on the brain tissues oxidative damage in pentylenetetrazole (PTZ)-induced seizures model was investigated. Materials & methods: Male Wistar rats were divided into 5 groups and treated: Control (saline), PTZ and three doses of the Apium graveolens extract (100, 500 and 1000 mg/kg) before PTZ. Latency to the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The brain tissues were then removed for biochemical measurements. Results: MCS and GTCS latencies in extract treated groups were significantly higher than that of PTZ group (P < 0.05-P< 0.01). The malondialdehyde (MDA) levels in the brain tissues of PTZ group were significantly higher than that of control animals (P < 0.01-P< 0.001). Pretreatment with the extract resulted in a significant reduction in the MDA levels (P < 0.05-P< 0.001). Following PTZ administration, a significant reduction in total thiol content was observed in the brain tissues (P < 0.05- P < 0.01). Pretreatment with the extract was not effective to prevent from the lowering effects of PTZ- induced seizures on total thiol concentrations in the brain tissues. Conclusion: The present study showed that aqueous extract of Apium graveolens aerial parts possess anticonvulsant activity. This activity is accompanied by an antioxidant effect in the brain.

Intracerebroventricular administration of cigarette smoke condensate induced generalized seizures reduced by muscarinic receptor antagonist in rats

Tobacco smoking is considered the greatest risk factor for early death caused by noncommunicable diseases. Currently, there are more than one billion tobacco smokers in the world predisposed to many diseases including heart attack, stroke, cancer, and premature birth or birth defects related to the consumption of cigarettes. However, studies on the association between tobacco smoking and seizures or epilepsy are insufficient and not well documented. In the present study, the authors examined the convulsive effects of the intracerebroventricular administration of cigarette smoke condensate (CSC, 2μl/Rat) in rats and compared it with the intensity of seizures in the kainic acid (KA)-induced seizure model of epilepsy. The role of the cholinergic system was also investigated by testing the effect of the muscarinic acetylcholine receptors (mAChRs) antagonist atropine (2ml/kg) on CSC-induced seizures.The results indicate that a central injection of CSC produces an epileptic behavior similar to that induced by KA, the similarities include the following parameters: time latency of seizures, latency and duration of tonic–clonic seizures, duration of seizures, survival, and tonic–clonic rate. However, a pretreatment with atropine reduced seizures and all their parameters.