Electroshock-induced Convulsions Research Articles

Screening of Phyllanthus Niruri Leaf Phytoconstituents by Insilico and in vivo Methods for Anticonvulsant Activity

Background: In the present study, we evaluated anticonvulsant activity of Phyllanthus niruri leaves powder by Insilico and in vivo methods. A molecular docking investigation of leaf components with certain proteins associated with diseases was carried out using Schrodinger Maestro (v13.0) software. Materials and Methods: Higher scores were also seen in the molecular docking data when compared to typical medications that are easily accessible. Invivo activity was carried out by 1 method i.e., Maximal Electroshock-Induced Convulsions. Results and Discussion: The animals were then treated with 100mg/kg body weight i.p of Estradiol syrup formulation. According to the findings of the acute toxicity trials, estradiol was not harmful in nature on 300mg/kg concentration by showing 80% cell viability. The number of viable animals tends to decrease as the concentration of Estradiol increases. Conclusion: Phyllanthus niruri leaves powder exhibited anticonvulsant activity in Maximal Electroshock Induced convulsion method.

Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitro and Computational Studies

Epilepsy is a chronic neurodegenerative disease characterized by multiple seizures, hereto 35% of patients remain poor responders. Phenytoin (PHT; 20 and 40 mg/kg) and thymoquinone (THQ; 40 and 80 mg/kg) were given alone and as a low dose combination for 14 days (p.o), prior to challenge with maximal electroshock (MES; 180 mA, 220 V, 0.2 s). Apart from observing convulsions, hippocampal mTOR, IL-1β, IL-6 and TNF-α levels were measured. Hippocampal histomorphological analysis was also conducted. In vitro cell line studies and molecular docking studies were run in parallel. The results revealed the synergistic potential of the novel duo-drug combination regimen: PHT (20 mg/kg) and THQ (40 mg/kg) against MES-induced convulsions. MES amplified signaling through mTOR, and inflated the levels of proinflammatory markers (IL-1β, IL-6 and TNF-α), which was significantly averted (p < 0.001) with the said drug combination. The computational studies revealed that PHT and THQ cooperatively bind the active site on Akt (upstream target of m-TOR) and establish a good network of intermolecular interactions, which indicates the sequential inhibition of PI3K/Akt/m-TOR signaling with the combination. The combination also increased cell viability by 242.81% compared to 85.66% viability from the the toxic control. The results suggest that the PHT and THQ in combination possesses excellent anticonvulsant and neuroprotective effects.

EVALUATION OF ANTICONVULSANT ACTIVITY OF CALLISTEMON CITRINUS (CURTIS) SKEELS (MYRTACEAE) VOLATILE OIL

The use of medicinal plants is on the rise due to the increase of various diseases and shortcomings of orthodox medicine. For many ailments including convulsion, conventional medicine has not been able to find a lasting solution. This study was directed towards assessing the ethnomedicinal use of Callistemon citrinus leaves in the management of convulsion. The volatile oil of the leaves was extracted and an acute toxicity test was carried out following Lorke’s description. Maximal electroshock (MES), strychnine and pentylenetetrazol anticonvulsant methods were used. Separate groups of albino mice were given 200, 400 and 800 mg/kg doses of the volatile oil. Drug solutions; 30 mg/kg phenobarbitone for MES and 2 mg/kg diazepam for strychnine and pentylenetetrazol models were administered as a positive control. The start of tonic leg extension, duration and percentage mortality was recorded. Doses of 200 and 400 mg/kg significantly (P&lt;0.05) inhibited seizure in the mice with scores of 40 % each in the MES model. There was a dose-dependent reduction in the duration of seizures with 68.47, 70.27 and 81.08 % reductions in the pentylenetetrazol model. No significant coverage was given in the strychnine model. C. citrinus oil protected the mice against pentylenetetrazol and maximal electroshock-induced convulsion hence could contribute to the medical treatment of epilepsy.

Anticonvulsant Activity of Helianthus tuberosus Against Maximal Electroshock Induced Convulsions in Rats

Epilepsy is an episodic brain dysfunction featured by recurring erratic spontaneous seizures followed by cognitive, social, neurobiological, and psychological consequences. Conventional anti-epileptic drugs are associated with several untoward effects, and hence long-term treatment compliance is a major problem in the management of epilepsy. Herbal drugs have shown promising efficacy as potent anticonvulsants in the past few years. In light of this, the anticonvulsant effect of alcoholic extract of leaves of Helianthus tuberosus (AHT) against maximal electroshock (MES) induced convulsions was investigated. In the present investigation, an indigenous plant, H. tuberosus was studied for its protective effect against maximal electroshock (MES) induced convulsions in Wistar albino rats. The rats were pre-treated with different doses (100, 200, 400 mg/kg) of alcoholic extract of leaves of H. tuberosus for 14 days, and then, they were subjected to maximal electroshock seizures (40 mA for 0.2 seconds) treatment. Alcoholic extract of leaves of H. tuberosus at the dose of 400 mg/kg significantly reduced the duration of hind limb extension and the protection of rats against maximal electroshock-induced seizures. The reference standards phenytoin (20 mg/kg) provided complete protection. Thus, the present study revealed an anticonvulsant effect of H. tuberosus against maximal electroshock-induced convulsions in rats.

Protective Effect of Cucurbita maxima against Maximal Electroshock Induced Convulsions

In the present investigation, an indigenous plant, Cucurbita maxima was studied for its protective effect against maximal electroshock (MES) induced convulsions in Wistar albino rats. The rats were pretreated with different doses (100, 200, 400 mg/kg) of hydroalcoholic extract of seeds of Cucurbita maxima for 14 days and then, they were subjected to maximal electroshock seizures (40 mA for 0.2 sec) treatment. Hydroalcoholic extract of Cucurbita maxima seeds at 200 and 400 mg/kg doses significantly reduced the duration of hind limb extension along with the protection of rats against maximal electroshock induced seizures. The reference standard i.e., phenytoin (20 mg/kg) provided complete protection. Thus, present study revealed anticonvulsant effect of Cucurbita maxima against maximal electroshock-induced convulsions in rats.

Design, synthesis and pharmacological profile of (−)-verbenone hydrazones

AbstractA series of novel (−)-verbenone hydrazones was designed and synthesized via condensation of terpenoid with hydrazides derived from phenoxyacetic acid. The structure of target compounds was confirmed by 1H-NMR and 13C-NMR analysis, Raman and FT-IR spectroscopy, electrospray ionization method and fast atom bombardment (FAB) mass spectrometry. Thermal properties of (−)-verbenone hydrazones 3a–3e were estimated by differential scanning calorimetry and their purity by HPLC coupled to mass spectrometry. Verbenone hydrazones were revealed to exist as Z/E geometrical isomers about C═N bond and cis/trans amide conformers. Verbenone derivatives were estimated as potential anticonvulsant agents after their oral administration against pentylenetetrazole and maximal electroshock-induced seizures in mice. Analgesic effect of hydrazones was studied by topical application on models of allyl isothiocyanate and capsaicin-induced pain. The present findings indicate that verbenone hydrazones contribute to seizure protection both at short (6 h) and long (24 h) time periods by blocking chemical- and electroshock-induced convulsions. Binding of compounds 3a–3e to TRPA1/TRPV1 ion channels was suggested as a feasible mechanism explaining their significant analgesic activity.

Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy

HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity. KRM-II-81 was active against electroshock-induced convulsions in mice, pentylenetetrazole (PTZ)-induced convulsions in rats, elevations in PTZ-seizure thresholds, and amygdala-kindled seizures in rats with efficacies greater than that of diazepam. KRM-II-81 was also active in the 6 Hz seizure model in mice. Structural analogs of KRM-II-81 but not the ester, HZ-166, were active in all models in which they were evaluated. We further evaluated KRM-II-81 in human cortical epileptic tissue where it was found to significantly-attenuate picrotoxin- and AP-4-induced increases in firing rate across an electrode array. These molecules generally had a wider margin of separation in potencies to produce anticonvulsant effects vs. motor impairment on an inverted screen test than did diazepam. Ester bioisosters of HZ-166 are thus presented as novel agents for the potential treatment of epilepsy acting via selective positive allosteric amplification of GABAA signaling through α2/α3-containing GABA receptors. The in vivo data from the present study can serve as a guide to dosing parameters that predict engagement of central GABAA receptors.

Psychopharmacological Evaluation of Alkaloidal Fraction of Desmodium gangeticum

Desmodium gangeticum D.C. (Salpani; family-Fabaceae) has been traditionally used as nervine tonic. Previous studies have shown antiamnesic activity of alkaloidal fraction (AF) of the plant. Thus, it was envisaged to subject AF (25 or 50 mg/kg, p.o.) for antianxiety, anticonvulsant, antidepressant, locomotor and hypnotic activities using well established models. AF exhibited significant antianxiety activity with respect to control using elevated plus maze model but the activity was not comparable to the standard drug, diazepam (2 mg/kg, p.o.). AF (50 mg/kg, p.o.) significantly reduced immobility time in forced swim test but did not stimulate locomotor activity of mice in open field test, suggesting its specific antidepressant activity. AF, at the doses of 25 and 50 mg/kg, reduced mean duration of tonic extensor phase to 15.25 and 14.55 sec, respectively, with respect to control (22.15 sec) but showed only 50% protection of mice from mortality due to maximal electroshock-induced convulsions. AF was found to be devoid of hypnotic activity as it could not potentiate duration of sleep in mice treated with thiopentone sodium. AF of D. gangeticum roots exerts mild CNS depression without causing sedation and possesses strong antidepressant activity.

Evaluation of the Effect of Naringenin on Pentylenetetrazole and Maximal Electroshock-Induced Convulsions in Mice

Background: Naringenin is a flavonoid with several different biological effects in central nervous system. As mentioned, naringenin has neuroprotective, memory enhancing, anti-inflammatory and antioxidant effects. Objectives: In this study, we investigated effects of naringenin on pentylenetetrazole and maximal electroshock-induced seizures in mice. Methods: Naringenin was administered at doses of 50, 100 and 200 mg/kg intraperitoneally in two models of seizure. Thirty minutes after different doses of naringenin, phenytoin or diazepam and vehicle, the animal received pentylenetetrazole or current stimulus by an electroconvulsiometer. Results: In maximal electroshock model, naringenin 200 mg/kg reduced the duration of hind limb tonic extension. In pentylenetetrazole seizure model all doses of naringenin increased the latency for convulsion and latency for Straub's tail but only naringenin 200 mg/kg showed significant reduction in duration of myoclonic seizure. Conclusions: According to the results, naringenin showed significant anticonvulsant and neuroprotection activity in two pentylenetetrazole and electroshock models of convulsion in mice and these effects may be mediated by antioxidant properties, agonist activity on GABAA receptors and weakening of glutamate transmission.

Evaluation of the Effect of Naringenin on Pentylenetetrazole and Maximal Electroshock-Induced Convulsions in Mice

Background: Naringenin is a flavonoid with several different biological effects in central nervous system. As mentioned, naringenin has neuroprotective, memory enhancing, anti-inflammatory and antioxidant effects. Objectives: In this study, we investigated effects of naringenin on pentylenetetrazole and maximal electroshock-induced seizures in mice. Methods: Naringenin was administered at doses of 50, 100 and 200 mg/kg intraperitoneally in two models of seizure. Thirty minutes after different doses of naringenin, phenytoin or diazepam and vehicle, the animal received pentylenetetrazole or current stimulus by an electroconvulsiometer. Results: In maximal electroshock model, naringenin 200 mg/kg reduced the duration of hind limb tonic extension. In pentylenetetrazole seizure model all doses of naringenin increased the latency for convulsion and latency for Straub's tail but only naringenin 200 mg/kg showed significant reduction in duration of myoclonic seizure. Conclusions: According to the results, naringenin showed significant anticonvulsant and neuroprotection activity in two pentylenetetrazole and electroshock models of convulsion in mice and these effects may be mediated by antioxidant properties, agonist activity on GABAA receptors and weakening of glutamate transmission.

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Differential Effects of Meloxicam on Pentylenetetrazole- and Maximal Electroshock-Induced Convulsions in Mice

Background: Epilepsy is a group of disorders associated with the abnormal electrical activity of different regions of the brain. The use of anticonvulsant drugs is limited because of their low efficacy, side effects, and toxicity. Therefore, research on new drugs for epilepsy is required. Meloxicam is a non-steroidal anti-inflammatory drug with several biological effects, such as antioxidant, neuroprotective, and anti-inflammatory. Objectives: Earlier studies gave conflicting reports on the effect of cyclooxygenase inhibitors on seizures. Accordingly, this study was designed to evaluate the effects of meloxicam on pentylenetetrazole (PTZ) and maximal electroshock (MES) models of convulsions Methods: For each model of convulsion, 48 mice were randomly divided into 6 groups of 8 animals. Group I in two models of convulsions were considered as the control group and the intraperitoneally (i.p.) received vehicle (10 mL/kg). Group II in the PTZ model received the reference anticonvulsant drug, diazepam (1 mg/kg, i.p.), and group II in the MES model was treated with phenytoin (25 mg/kg, i.p.). Groups III - VI in two models of convulsions received four different doses of meloxicam (2.5, 5, 10, and 20 mg/kg, i.p.), respectively. Thirty minutes later, convulsion was induced by PTZ (85 mg/kg, i.p.) in PTZ model and by using ear-clip electrodes in the MES model of convulsion. Results: In the PTZ model, meloxicam showed a significant delayed onset of seizures, Straub’s tail, and myoclonic seizure. Different doses of meloxicam reduced the mortality of animals in the PTZ model. In the MES model, meloxicam did not change the duration of hindlimb tonic extension and caused the death of animals unlike the PTZ model. Conclusions: According to the results, meloxicam has differential effects on two PTZ and MES models of seizure. The anticonvulsant and neuroprotective effects of meloxicam on the PTZ model may be mediated by anti-inflammatory and antioxidant properties. In the MES model, meloxicam did not show any beneficial effect and aggravated convulsive behavior. In the PTZ model, prostaglandins could be involved in the induction of convulsion. Conversely, in the MES model, prostaglandins may attenuate the severity of seizure at the basal level and prevent the development of convulsions. Nevertheless, more studies must be conducted to clarify the mechanisms of action of prostaglandins and meloxicam in the two PTZ and MES models of seizure.

Differential Effects of Meloxicam on Pentylenetetrazole- and Maximal Electroshock-Induced Convulsions in Mice

Background: Epilepsy is a group of disorders associated with the abnormal electrical activity of different regions of the brain. The use of anticonvulsant drugs is limited because of their low efficacy, side effects, and toxicity. Therefore, research on new drugs for epilepsy is required. Meloxicam is a non-steroidal anti-inflammatory drug with several biological effects, such as antioxidant, neuroprotective, and anti-inflammatory. Objectives: Earlier studies gave conflicting reports on the effect of cyclooxygenase inhibitors on seizures. Accordingly, this study was designed to evaluate the effects of meloxicam on pentylenetetrazole (PTZ) and maximal electroshock (MES) models of convulsions Methods: For each model of convulsion, 48 mice were randomly divided into 6 groups of 8 animals. Group I in two models of convulsions were considered as the control group and the intraperitoneally (i.p.) received vehicle (10 mL/kg). Group II in the PTZ model received the reference anticonvulsant drug, diazepam (1 mg/kg, i.p.), and group II in the MES model was treated with phenytoin (25 mg/kg, i.p.). Groups III - VI in two models of convulsions received four different doses of meloxicam (2.5, 5, 10, and 20 mg/kg, i.p.), respectively. Thirty minutes later, convulsion was induced by PTZ (85 mg/kg, i.p.) in PTZ model and by using ear-clip electrodes in the MES model of convulsion. Results: In the PTZ model, meloxicam showed a significant delayed onset of seizures, Straub’s tail, and myoclonic seizure. Different doses of meloxicam reduced the mortality of animals in the PTZ model. In the MES model, meloxicam did not change the duration of hindlimb tonic extension and caused the death of animals unlike the PTZ model. Conclusions: According to the results, meloxicam has differential effects on two PTZ and MES models of seizure. The anticonvulsant and neuroprotective effects of meloxicam on the PTZ model may be mediated by anti-inflammatory and antioxidant properties. In the MES model, meloxicam did not show any beneficial effect and aggravated convulsive behavior. In the PTZ model, prostaglandins could be involved in the induction of convulsion. Conversely, in the MES model, prostaglandins may attenuate the severity of seizure at the basal level and prevent the development of convulsions. Nevertheless, more studies must be conducted to clarify the mechanisms of action of prostaglandins and meloxicam in the two PTZ and MES models of seizure.

A Review of Novel Formulation Strategies to Enhance Oral Delivery of Zaleplon

Zaleplon is a pyrrazolopyrimidine which is recommended for the treatment of insomnia and pentylenetetrazole/ electroshock-induced convulsions is an effective anticonvulsant which potential acts on the GABA receptor. The poor oral bioavailability of zaleplon (~30%) is due to the low solubility which in turn amputates the dissolution of the drug, restricts gastric absorption and first-pass metabolism. It is now withdrawn from the market due to the high dose and inefficient therapeutic activity. This review focuses on the various drug systems of zaleplon such as solid dispersions, self-nanoemulsifying, solid dispersions, proliposomes and solid lipid nanoparticles to enhance the oral bioavailability.

Absence of anticonvulsant activity in Asparagus adscendens Roxb. hydroethanolic root extract against acute pentylenetetrazol and maximal electroshock-induced convulsion mice models

Introduction: The use of Asparagus adscendens (family:Liliaceae) root powder has been reported traditionally for the treatment of epilepsy. But, it is yet to be validated pharmacologically. Therefore, the present study was undertaken to explore the anticonvulsant effect of the roots in the experimental animal models of convulsions. Materials and Methods: The anticonvulsant effect of hydroethanolic root extract of A. adscendens (AAE) was studied at 25, 50, and 100 mg/kg; intraperitoneally (i.p.) in maximal electroshock (MES), and at 25, 50, 100, and 200 mg/kg; i.p. doses in pentylenetetrazol (PTZ) test in mice. The duration of tonic hind limb extension (s) and latency to tonic-clonic convulsions (min) was noted in MES and PTZ tests, respectively. Phenytoin (25 mg/kg; i.p.) and diazepam (5 mg/kg; i.p.) served as reference standards in MES and PTZ tests, respectively. Percentage mortality was also noted. Results: The AAE treatment did not show any protective effect with regard to induction and duration of tonic hind limb extensor in MES test and latency to tonic-clonic convulsions in PTZ test, as compared to their respective controls. Conclusions: The results obtained from the experiments indicate that the AAE lacks anticonvulsant activity in MES- and PTZ-induced convulsion tests.

PP07.1 – 2308: Attenuation of the anticonvulsant effects of classical antiepileptic drugs against electroshock-induced convulsions in mice fed the ketogenic diet

Objective To investigate whether the KD could affect the anticonvulsant activity and pharmacokinetic properties of several AEDs in a model of generalized tonic-clonic epilepsy. Methods Male Swiss mice weighing 20–25 g were used for experiments. Mice were fed the KD for 2 weeks ( http://www.bioserv.com/product/F3666.html , 6:1 ratio of fat to protein + carbohydrates); control mice were receiving a standard rodent diet. The following AEDs were studied: carbamazepine, phenobarbital, phenytoin, and valproate. Electroconvulsions were induced by applying an alternating current via ear-clip electrodes in two methodologically different experimental approaches: maximal electroshock seizure threshold (MEST) test and maximal electroshock seizure (MES) test. Results The KD decreased the electroconvulsive threshold in the MEST test in mice, i.e. 47% decrease of the CS50 value from 7.29 to 3.86 mA, p Conclusion Though the KD has proven efficacy in clinical practice, it lowers the electroconvulsive threshold in the MEST test in mice. Moreover, the KD attenuates the anticonvulsant efficacy of the AEDs tested. This paradoxical effect of AEDs losing their anticonvulsant efficacy in mice fed the KD may be reflective of a higher energy state produced by the KD leading to a facilitated spread of electroconvulsions in the brain. It is concluded that that the MES and MEST tests may not be suitable for studying the anticonvulsant properties of the KD in mice.

Evaluation of Antiepileptic Activity of Methanolic Leaves Extract of &lt;i&gt;Tragia involucrata&lt;/i&gt; Linn. in Mice

The present investigation was aimed to study an antiepileptic activity of methanolic extract of Tragia involucrata Linn in mice. In vivo screening models like maximal electroshock-induced convulsion (MES), pentylenetetrazole (PTZ) and picrotoxin (PTX) induced models are used to evaluate the antiepileptic effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH). In the MES induced convulsion, methanolic extract of Tragia involucrata (METI) at high dose (800 mg/kg body weight), showed high significant inhibition on tonic hind limb extension (THLE, 6.83 ±0.30***) and decrease in duration of stupor period (108.7 ±6.53***). In PTZ and PTX induced model METI (400 mg/kg and 800 mg/kg) showed significant delay on the onset of convulsions, decreased duration of convulsion and reduced mortality significantly. It also showed significant decrease in brain MDA level in lipid peroxidation profile, and increase in the brain glutathione levels in mice against PTZ induced convulsion. The results confirmed that Tragia involucrata Linn possesses dose dependent antiepileptic activity.

Evaluation of Antiepileptic Activity of Methanolic Leaves Extract of &lt;i&gt;Tragia involucrata&lt;/i&gt; Linn. in Mice

The present investigation was aimed to study an antiepileptic activity of methanolic extract of Tragia involucrata Linn in mice. In vivo screening models like maximal electroshock-induced convulsion (MES), pentylenetetrazole (PTZ) and picrotoxin (PTX) induced models are used to evaluate the antiepileptic effects of the extracts. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH). In the MES induced convulsion, methanolic extract of Tragia involucrata (METI) at high dose (800 mg/kg body weight), showed high significant inhibition on tonic hind limb extension (THLE, 6.83 ±0.30***) and decrease in duration of stupor period (108.7 ±6.53***). In PTZ and PTX induced model METI (400 mg/kg and 800 mg/kg) showed significant delay on the onset of convulsions, decreased duration of convulsion and reduced mortality significantly. It also showed significant decrease in brain MDA level in lipid peroxidation profile, and increase in the brain glutathione levels in mice against PTZ induced convulsion. The results confirmed that Tragia involucrata Linn possesses dose dependent antiepileptic activity.

Some Central Nervous System Effects of the aqueous Extract of the Leaves of &lt;i&gt;Phyllanthus Amarus&lt;/i&gt; Schum, (Euphorbiaceae).

The leaves of Phyllanthus amarus is used in Southern Nigeria to treat variety of diseases including epilepsy. The aqueous extract of the leaves of Phyllanthus amarus was investigated for some central nervous system effects. Two animals models (maximal electroshock and pentylenetetrazol-induced convulsion), were used for the anticonvulsant screening in mice. The influences of the extract on barbiturate-induced sleeping time and on motor coordination were investigated in rats and mice respectively. The extract protected the animals against maximal electroshock-induced convulsion at the doses of 100mg/kg and 200mg/kg that were used, but could not protect the animals against pentylenetetrazol-induced convulsion at these two doses. However, higher doses of 500mg/kg and 1000mg/kg only provided a marginal protection of 20% and 40% to the animals against pentylenetetrazol-induced convulsion. The extract neither prolonged barbiturate-induced sleeping time nor did it impair the motor co-ordination ability of the animals on the Ugo Basile rotarod rotating at 6rpm. The results have shown that the aqueous extract of the leaves of Phyllanthus amarus contains some active principles that have anticonvulsant effect and protect mainly against maximal electroshock-induced convulsion, without depressing the central nervous system.Key Words: Phyllanthus amarus, Anticonvulsant Activity, Sleeping Time, Sedation

Anticonvulsant effects of agomelatine in mice

Agomelatine is a potent MT1 and MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist. We analyzed whether agomelatine has anticonvulsant properties. The anticonvulsant activity of agomelatine (25, 50 or 75mg/kg, i.p.) was evaluated in mouse models of pentylenetetrazole (PTZ-85mg/kg, i.p.), pilocarpine (400mg/kg, i.p.), picrotoxin (7mg/kg, i.p.), strychnine (75mg/kg, i.p.) or electroshock-induced convulsions. In the PTZ-induced seizure model, agomelatine (at 25 or 50mg/kg) showed a significant increase in latency to convulsion, and agomelatine (at 50 or 75mg/kg) also increased significantly time until death. In the pilocarpine-induced seizure model, only agomelatine in high doses (75mg/kg) showed a significant increase in latency to convulsions and in time until death. In the strychnine‐, electroshock‐ and picrotoxin-induced seizure models, agomelatine caused no significant alterations in latency to convulsions and in time until death when compared to controls. Our results suggest that agomelatine has anticonvulsant activity shown in PTZ‐ or pilocarpine-induced seizure models.