Strychnine-induced Seizure Model Research Articles

Comparative anticonvulsant studies on ethanol and ethyl acetate extracts of Zingiber Officinale Roscoe rhizome in mice and chicks

Epilepsy represents a major public health problem in low- and middle-income countries of Africa and Latin America where over 75% of patients do not have access to treatment. Aqueous and ethanol extracts of Zingiber officinale have been reported previously to have anticonvulsant effect. This study was aimed at comparing the anticonvulsant effect of ethanol and ethylacetate extracts of Zingiber officinale rhizomes in mice and chicks. Fresh rhizomes of Zingiber officinale (ginger) were collected, size reduced, air-dried under shade and extracted with ethanol and ethylacetate using cold maceration. Anticonvulsant activity of the extracts was determined by maximal electroshock stimulation (MES) in chicks, pentylenetetrazole (PTZ) and strychnine induced seizure models in mice. The ethanol and ethylacetate extracts of the ginger at doses of 50, 100 and 200 mg/kg were administered intraperitoneally 30 minutes prior to the induction of seizures. Both ethanol and ethylacetate extracts of Zingiber officinale at the doses of 100 and 200 mg/kg produced a dose-dependent protection against tonic hind limb extension seizure in MES model, significantly (p< 0.01) decreased the onset of clonic seizure in the strychnine model and significantly (p<0.001) prolonged the mean time of death in the PTZ model. In addition, the ethanol extract at the doses of 100 and 200 mg/kg significantly (p<0.001) decreased the onset of seizure in the PTZ model. It might be concluded that both ethanol and ethylacetate extracts of Zingiber officinale contain biologically active compounds with significant anticonvulsant activity, but the ethanol extract produced a better anticonvulsant activity.

Potential Mechanisms Involved in the Anticonvulsant Effect of Methanol Extract of Pyrenancantha staudtii in Mice.

To determine the potential effect of Pyrenancantha staudtii extract on experimentally induced seizures in mice and to evaluate the role of benzodiazepines, naloxone, and serotonin within these pathways. Animal behaviours were evaluated using open field, hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin-, or strychnine-, or isoniazid-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant, three notable antagonists (flumazenil, 3 mg/kg; naloxone 5 mg/kg, i.p., and cyproheptadine, 4 mg/kg, i.p) were used. The results revealed a significant (p < 0.05) reduction in the frequency of rearing and grooming episodes compared with the control. The extract of P. staudtii potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. P. staudtii stem bark extracts significantly (p<0.05) prolonged the onset of a seizure and attenuated the duration of seizure in a dose-dependent manner in picrotoxin- and or isoniazid-induced seizures. While, P. staudtii stem bark extract at all doses (100, 200, and 400 mg kg-1) though significantly prolonged the onset of action, but did not confer any significant changes on the duration, as well as mortality in this strychnine-induced seizure model. However, the anticonvulsant activity of the methanolic extract of P. staudtii was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) and naloxone (opioid receptor antagonist) but not cyproheptadine (5-HT2 receptor antagonist) in picrotoxin-induced convulsion. The data obtained suggest that methanol extract of P. staudtii possessed significant anticonvulsant effect, thereby confirming the traditional uses of P. staudtii in the treatment of epilepsy; mechanisms of which could involve the interaction with GABAergic and or opioidergic system.

Evaluation and Comparison of Anti-Epileptic Activity of Methanolic Extracts of Seeds of Cuminum Cyminum L. and Centratherum Anthelminticum L. in Seizure Model

Objective: Evaluation and comparison of anti-epileptic activity of methanolic extracts of seeds of Cuminum cyminum L. and Centratherum anthelminticum L. in strychnine-induced seizure model.&#x0D; Methods: The study was conducted in the Department of Pharmacology, University of Karachi. After 15 days of dosing, experiment was performed. A total of 40 healthy mice were selected from animal house of the Pharmacology department, University of Karachi, and were equally divided into four groups. Group 01 was on DMSO (dimethyl sulphoxide) organic solvent as control; Group 02 was on methanolic extract of Cuminum cyminum L. (500 mg/kg); Group 03 was on methanolic extract of Centratherum anthelminticum L. (200 mg/kg) and Group 04 was on reference drug diazepam (3 mg/kg). On the day of experiment, after giving doses of DMSO, methanolic extract of Cuminum cyminum L., methanolic extract of Centratherum anthelminticum L. and diazepam, respectively to all groups, strychnine was administered and animals were observed for latency period and duration of Mortality rate was also evaluated.&#x0D; Results: Group 02 and 03, receiving methanolic extracts of Cuminum cyminum L. and Centratherum anthelminticum L. showed significant seizure protection as observed by delayed seizure onset (p &lt;0.001) and decreased total duration of convulsions in groups 02 and 03 (p£ 0.01, p£ 0.05) respectively. The mortality rate also decreased significantly (p £ 0.05) in comparison with group 01.&#x0D; Conclusion: Anticonvulsant activity of methanolic extracts of Cuminum cyminum L. and Centratherum anthelminticum L. could be due to their antioxidant activity and further enhanced by potentiation of GABAergic and glycinergic activity. Further studies are required to confirm exact mechanism of action.

Anti-epileptic activity of Nelumbo nucifera fruit.

Epilepsy is the most commonly encountered neurological disorder affecting around 70 million people worldwide, out of which approximately 80% belongs to developing countries. Several shortcomings appeared with the use of conventional antiepileptic agents like, inadequate seizure control, side effects and cost which limit their use. Thus extensive studies are necessary to investigate the pharmacological effects of plants, which would facilitate discovery of novel drugs from herbal source permitting their use to benefit mankind. Hence current study was focused to evaluate the anti-epileptic potential of Nelumbo nucifera fruit in order to ascertain its therapeutic potential. Anti-epileptic activity was assessed using strychnine induced seizure model in 35 male Wister rats divided in five groups i.e. control, reference and 3 test groups. Each group was composed of 7 animals and was given 2% gum tragacanth (control), diazepam 1mg/kg PO (reference) and N. nucifera fruit 50, 100 and 200mg/kg PO (test) OD for 15days. N. nucifera fruit extract at 200mg/kg exhibited extremely noteworthy delay in the inception of convulsions as compared to control however duration of convulsions was increased significantly but intensity of convulsions was reduced resulting in better survival rate i.e. 42.85% which was comparable to diazepam. Therefore it can be concluded that N. nucifera fruit may be valuable in managing epilepsy but further studies are required on large number of animals to confirm these findings.

Phenylalanine derivatives with modulating effects on human α1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats

The critical role of α1-glycine receptor (α1-GLYRs) in pathological conditions such as epilepsy is well known. In the present study, structure-activity relations for a series of phenylalanine derivatives carrying selected hydrogen bond acceptors were investigated on the functional properties of human α1-GLYR expressed in Xenopus oocytes. The results indicate that one particular substitution position appeared to be of special importance for control of ligand activity. Among tested ligands (1-8), the biphenyl derivative (2) provided the most promising antagonistic effect on α1-GLYRs, while its phenylbenzyl analogue (5) exhibited the highest potentiation effect. Moreover, ligand 5 with most promising potentiating effect showed in-vivo moderate protection when tested in strychnine (STR)-induced seizure model in male adult rats, whereas ligand 2 with highest antagonistic effect failed to provide appreciable anti(pro)convulsant effect. Furthermore, ligands 2 and 5 with the most promising effects on human α1-GLYRs were examined for their toxicity and potential neuroprotective effect against neurotoxin 6-hydroxydopamine (6-OHDA). The results show that ligands 2 and 5 possessed neither significant antiproliferative effects, nor necrotic and mitochondrial toxicity (up to concentration of 50μM). Moreover, ligand 2 showed weak neuroprotective effect at the 50μM against 100μM toxic dose of 6-OHDA. Our results indicate that modulatory effects of ligands 2 and 5 on human α1-GLYRs as well as on STR-induced convulsion can provide further insights for the design of therapeutic agents in treatment of epilepsy and other pathological conditions requiring enhanced activity of inhibitory glycine receptors.

Evaluation of anticonvulsant effects of methanolic extract of &lt;i&gt;Olax subscorpioidea&lt;/i&gt; Oliv. leaves in chicks and mice

Preparations of Olax subscorpioidea have been used in the Nigerian traditional medicine for the management of convulsions, mental illness, pains, cancer and microbial infections. The efficacy of the leaves of this plant in management of convulsions has been widely acclaimed among the Igala communities of North-Central part of Nigeria and therefore, this study was aimed at examining the anticonvulsant effects of methanolic extract of O. subscorpioidea (MEOS) leaves in order to provide scientific basis for its use in management of convulsions. Phytochemical screening and evaluation of intraperitoneal median lethal dose of the extract was carried out. Anticonvulsant activity of MEOS was evaluated in chicks using maximal electroshock test, and in mice using pentylenetetrazole and strychnine-induced seizure models at doses of 100, 200 and 400 mg/kg. The intraperitoneal median lethal dose of MEOS was estimated to be 3800 mg/kg body weight in mice. MEOS at doses of 100 and 200 mg/kg provided 30 and 70% protection against maximum electroshock induced seizures respectively. The extract also significantly (p < 0.05) increased the mean latency to seizures in a dose dependent manner. MEOS at 100 mg/kg provided 50% protection against strychnine-induced seizures. A significant increase (p < 0.01) and (p < 0.05) in the mean onset of strychnine-induced seizures was also observed with MEOS at doses of 200 and 400 mg/kg respectively. These findings suggest that the methanolic extract of Olax subscorpioidea leaves possess anticonvulsant activity. Keywords : Anticonvulsant, Maximal Electroshock, Olax subscorpioidea , Pentylenetetrazole, Strychnine

Evaluation of anticonvulsant and neuroprotective effects of camel milk in strychnine-induced seizure model

ObjectiveTo discover the use of camel milk as an alternate medicine for the treatment and prevention of convulsions using strychnine-induced seizure model. MethodsThirty animals were divided into three equal groups. Group I was on distilled water, Group II was on camel milk for 15 days prior to experiment and Group III was on reference drug diazepam. On the day of experiment, strychnine was administered in all treatment groups after distilled water, camel milk and diazepam treatments respectively. Animals were observed for 30 min for latency of seizure onset, frequency of convulsions and duration of jerks. The mortality rate was also evaluated for each group. ResultsCamel milk treatment showed significant seizure protection as observed by delayed seizure onset (P ≤ 0.001), decreased total duration of convulsions (P ≤ 0.001) and mortality rate (P ≤ 0.001) when compared with Group I. ConclusionsAnticonvulsant activity of camel milk could be due to potentiation of glycinergic and GABAergic activities both. Antioxidant activity can also amplify its antiepileptic activity. Further studies are required to confirm the exact mechanism of action.

Anticonvulsant and Antioxidant Effects of Methanol Extract of Stems of &lt;i&gt;G. arborea Roxb.&lt;/i&gt;

&lt;p&gt;&lt;em&gt;Gmelina arborea &lt;/em&gt;Roxb. (Verbenaceae) is greatly valued plant reported in Indian traditional system of medicine for various ailments. In this study, anticonvulsant and antioxidant activity of methanolic extract of stems (MES) of &lt;em&gt;Gmelina arborea &lt;/em&gt;Roxb. was investigated. Protective effects were evaluated in pentylenetetrazole (PTZ) (60 mg/kg, s.c.) and strychnine (STR) (2 mg/kg, i.p.) induced seizure models in adult albino mice (250 mg/kg and 500 mg/kg) using diazepam as a standard.&lt;/p&gt;&lt;p&gt;Total phenolics and flavonoids content in MES were determined and antioxidant activity was evaluated by 1,1-diphenyl-2- picryl- hydrazyl (DPPH) radical scavenging activity, scavenging of hydrogen peroxide and through reducing power assay. The onset and duration of seizures (tonic-clonic convulsions), mortality rate and number of mice convulsing or not convulsing within the observation period were noted in PTZ and STR induced seizure models&lt;strong&gt;. &lt;/strong&gt;MES showed good reductive capability and free radical scavenging effects with IC&lt;sub&gt;50&lt;/sub&gt; 47.47 µg/ml for DPPH radical assay and 97.33 µg/ml for hydrogen peroxidescavenging in a dose dependent manner.MES at the dose of 500 mg/kg, exhibited maximum delay in onset of convulsions (8.188 min in PTZ and 11.81 min in STR induced seizures) in both the models with increased latency period.&lt;/p&gt;&lt;p&gt;The suppression of seizures by MES (500 mg/kg) might be observed due to enhanced gamma amino butyric acid neurotransmission in PTZ induced animals. The constituents of MES might also have glycine inhibitory potential to impart protection in STR induces seizures in our study. Further considerable presence of flavonoids and phenolic have provided good antioxidant activity as a supportive underlying mechanism for anticonvulsant effects. This study justifies the multilevel therapeutic uses of stem bark and heartwood of &lt;em&gt;G. arborea&lt;/em&gt; in Indian system of medicine.&lt;/p&gt;

Evaluation of neuropharmacological effects of aqueous leaf extract of Albizia glaberrima (Leguminosae) in mice

Ethnopharmacological relevanceAlbizia glaberrima is a shrub found in the deciduous forest and jungle of the coastal plain of West Africa. Preparations of the plant are used traditionally in the treatment of fever, pain and central nervous system disorders, including epilepsy. This study was conducted to investigate the neuropharmacological effects of the aqueous leaf extract of Albizia glaberrima in mice. Materials and methodsThe hole-board, elevated plus-maze, thiopentone-induced sleep (anxiolytic/sedative-hypnotic), traction, climbing, inclined screen (muscle relaxant), strychnine-, picrotoxin- and pentylenetetrazole (PTZ)-induced convulsion (anticonvulsant) tests were employed in this study. ResultsAlbizia glaberrima extract at 200mg/kg significantly increased the duration of head dips (p<0.05) and number of open arms entry (p<0.01) compared with control in the hole-board and elevated plus-maze tests, respectively. At 400mg/kg, Albizia glaberrima extract significantly reduced the number of sectional crossings relative to control. The extract at 400mg/kg significantly (p<0.05) increased the duration of sleep compared with control in the thiopentone-induced hypnosis test. Albizia glaberrima extract at 200mg/kg and diazepam (5mg/kg) significantly (p<0.05, 0.01) increased the post-treatment climbing time and reduced the latency to slide down in the climbing and inclined screen tests, respectively. The extract was not effective in the strychnine-induced seizure model, while in the picrotoxin test Albizia glaberrima extract at 100mg/kg significantly (p<0.05) reduced the duration of convulsion while reducing mortality at 400mg/kg, as was the case with diazepam (2mg/kg). The extract and diazepam significantly (p<0.01, 0.001) increased onset and reduced duration of convulsion, with significant level of protection against convulsion and reduction in mortality in the PTZ-induced seizure model. Preliminary phytochemical screening of the extract revealed the presence of phenols>tannins>saponins>flavonoids. The extract was found to be relatively non-toxic when administered p.o. up to 5000mg/kg and the LD50 was 398.11mg/kg when administered i.p. ConclusionsThe aqueous leaf extract of Albizia glaberrima possesses dose-dependent anxiolytic/muscle relaxant (low dose) and sedative-hypnotic/anticonvulsant (high dose) activities possibly mediated via enhancement of GABAergic inhibitory actions.

037 — (LIM0148) Proconvulsant activity of imipenem in the strychnine-induced seizure model in mice

037 — (LIM0148) Proconvulsant activity of imipenem in the strychnine-induced seizure model in mice

048 — (MEN0070) Anticonvulsant activity of acute treatment with manidipine in picrotoxin and strychnine-induced seizure models in mice

048 — (MEN0070) Anticonvulsant activity of acute treatment with manidipine in picrotoxin and strychnine-induced seizure models in mice

Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures.

Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.

The effects of the Brazilian ant Dinoponera quadriceps venom on chemically induced seizure models

Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5mg/kg) increased the time until the first seizure and the percentage of survival (155.4±27.7s/12.5%, p<0.05) compared to the control group (79.75±3.97s/0%), whereas endovenous treatment (0.1 and 0.5mg/kg) decreased the time until the first seizure (0.1mg/kg: 77.83±5.3s versus 101.0±3.3s in the control group; 0.5mg/kg: 74.43±3.9s versus 101.0±3.3s for the control group, p<0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the D. quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.

Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.)

This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L.) as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L.), using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle), standard (diazepam) and test (Trachyspermum ammi (L.) extract). Trachyspermum ammi (L.) demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L.) and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L.) showed antiepileptic activity, which may be due to the presence of thymol.

Central action of Araucaria angustifolia seed lectin in mice

Possible central nervous system effects of the gymnosperm lectin from Araucaria angustifolia seeds were studied in seizure and open field tests. Male Swiss mice were administered saline (control), lectin (0.1, 1, and 10 mg/kg), flumazenil (1 mg/kg), or diazepam (1 mg/kg) intraperitoneally. Lectin at the highest dose increased time to death in the pentylenetetrazole- and strychnine-induced seizure models as compared with control, but not in the pilocarpine model. In the open field test, lectin reduced locomotor activity at all doses tested, as did diazepam, when compared with control. These locomotor effects were reversed by flumazenil pretreatment. In conclusion, A. angustifolia lectin had a protective effect in the pentylenetetrazole- and strychnine-induced seizure models, suggestive of activity in the GABAergic and glycinergic systems, respectively, and also caused a reduction in animal movements, which was reversed by flumazenil, pointing to a depressant action mediated by a GABAergic mechanism.

Anticonvulsant activity of hydroalcoholic extracts from Erythrina velutina and Erythrina mulungu

The anticonvulsant effects of hydroalcoholic extracts (HAEs) from the stem bark of Erythrina velutina and Erythrina mulungu on pentylenetetrazole (PTZ) and strychnine-induced seizure tests and the potentiation of pentobarbital-induced sleeping time in mice with the extracts were examined in this study. These medicinal plants belong to the Fabaceae family and are popularly used in Brazil for their effects on the central nervous system. The extracts of Erythrina velutina (intraperitoneally or orally) and Erythrina mulungu (intraperitoneally) were administered in mice at single doses (200 or 400 mg/kg). While Erythrina velutina and Erythrina mulungu did not exhibit any protector effect in PTZ-induced seizures, at any dose, an increase in the latency of convulsion and in the death time was observed with both doses and routes of Erythrina velutina and at higher dose of Erythrina mulungu, in strychnine-induced seizure. No alteration was observed with Erythrina velutina and Erythrina mulungu on sleeping latency at both doses as compared to control (362.8 ± 59.5). However, the sleeping time was increased in both plants as compared to control (943.8 ± 129.6). In conclusion, we showed that the hydroalcoholic extracts of Erythrina velutina and Erythrina mulungu have anticonvulsant effects only in the strychnine-induced seizure model, suggesting their possible action in glycine system and a potentiation of pentobarbital sleeping time, suggesting depressant action in the central nervous system.