Tonic Hindlimb Extension Research Articles

Suvorexant, a Dual Orexin Receptor Antagonist, Protected Seizure through Interaction with GABAA and Glutamate Receptors.

Orexin can increase neuronal excitability and induce epileptic activity. In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 mL/kg), diazepam (2 mg/kg), and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ test, the latency to first minimal clonic seizure (MCS), latency to the first generalized tonic–clonic seizures (GTCS), total duration of seizure and also protection against mortality were evaluated. In MES, the hind limb tonic extension (HLTE) and the protection against mortality were recorded. In order to evaluate the role of GABAA in anticonvulsant effect of suvorexant, flumazenil was used and to investigate the role of glutamate, the protein levels of AMPAR and NMDAR were measured in hippocampus by western blotting. In PTZ model, suvorexant (200mg/kg) increased MCS and GTCS latencies. Suvorexant (100 and 200 mg/kg) decreased total duration of seizure compared to control group. In PTZ model, flumazenil inhibited the prolongation of seizure latency induced by suvorexant. In MES, the HLTE was decreased by suvorexant (100 and 200 mg/kg) and suvorexant was protected against mortality by 83.3%. Moreover, the protein levels of NMDAR and AMPAR were decreased by suvorexant. Suvorexant exerted anticonvulsant activity and in addition to its inhibitory effect on orexin receptors, this effect may be mediated, at least partly, through interaction with GABAA and glutamate receptors.

Anticonvulsant Effect of Alcea aucheri on Pentylenetetrazole and Maximal Electroshock Seizures in Mice.

Introduction:This study was designed to investigate the possible anticonvulsant effect of acute administration of an aqueous extract of flowers of Alcea aucheri (EFA) in two in vivo seizure models.Methods:Seizures were induced in male adult Swiss mice by administration of Pentylenetetrazol (PTZ) or Maximal Electroshock (MES). Mice were randomly subjected to receive saline, EFA (8.75–175 mg.kg−1), or diazepam intraperitoneally (i.p.) 15 or 30 min before PTZ injection. In another experiment, mice were treated (i.p.) with saline, EFA (8.75–350 mg.kg−1), or phenytoin 15 or 30 min before the MES test. Diazepam and phenytoin were used as reference drugs.Results:EFA (175 mg.kg−1) significantly increased the PTZ-induced seizure threshold compared with the saline control group 15 min after its administration. In the MES test, the extract (35 mg.kg−1) increased the latency to onset of tonic Hind Limb Extension (HLE) (seizure activity) compared with the saline group 15 min after treatment. Also, 30 min after treatment, EFA (35, 70, and 175 mg.kg−1) increased the latency to onset of the seizure, decreased the duration of the seizure (70 mg.kg−1), and decreased seizure occurrence (350 mg.kg−1) compared with those of the saline group. At both time points, the extract at all doses significantly reduced the mortality rate compared with the saline group.Conclusion:These findings provide evidence of a possible anticonvulsant effect of A. aucheri in PTZ and MES seizure models in mice.

Amelioration of Oxidative Stress and Neuroinflammation by Saroglitazar, A Dual PPARα/γ Agonist in MES Induced Epileptic Rats

Oxidative stress and neuroinflammatory process are implicated in pathophysiology of epilepsy as well as epileptogenesis. The α and γ isoform of peroxisome proliferator-activated receptors (PPAR) agonist has been reported to have antioxidant and anti-inflammatory functions. We hypothesized that saroglitazar, a dual PPAR-α and PPAR-γ agonist may ameliorate oxidative stress and neuroinflammatory process in MES induced epileptic rats. A total of 36 rats were randomized to different groups (n=6). Group I served as normal control, while in the remaining groups (group IV, V and VI) animals were pre-treated with saroglitazar for 15 days prior to inducing MES. Group I animals were pre-treated with vehicle and group-III with diazepam (2mg/kg). Epilepsy was induced in rats and time taken for onset of tonic hind limb extension (THLE), duration of THLE, duration of clonic phase and recovery time in seconds were noted. Brain SOD and MDA levels were assessed and immunohistochemical analysis was done to evaluate the expression of inflammatory marker COX-2. Pre-treatment with saroglitazar was effective against tonic clonic seizure in MES treated rats. SOD levels significantly increased and a significant reduction in MDA levels with a remarkable decrease in the uptake of COX-2 antibody were reported. Saroglitazar attenuated MES induced epilepsy and the probable underlying mechanisms are due to the inhibition of oxidative stress and neuroinflammation.

Novel effect of Arthrocen (avocado/soy unsaponifiables) on pentylenetetrazole-induced seizure threshold in mice: Role of GABAergic pathway

Arthrocen, an avocado/soy unsaponifiable (ASU)-containing agent, is now used in the clinic and has potentially to decrease joint inflammation and pain associated with mild to severe osteoarthritis. Phytosterols are the major component of Arthrocen with documented anti-inflammatory properties, antioxidant, and analgesic effects.Here, we evaluated ASU anticonvulsant effect by its oral administration in pentylenetetrazole (PTZ)-induced seizure threshold and Maximal Electroshock Seizure (MES) Models. Also, the involvement of N-methyl-d-aspartate (NMDA) receptor, benzodiazepine receptor, and nitric oxide (NO) pathway were studied in anticonvulsant effect of ASU in male NMRI mice. Acute administration of Arthrocen (150, 75, 30, 10 mg/kg) by oral gavage significantly (p < 0.001) increased the clonic seizure threshold induced by intravenous administration of PTZ. Nonspecific inducible NO synthase (NOS) inhibitor L-NAME (10 mg/kg) and a specific NMDA receptor antagonist MK-801 (0.05 mg/kg) did not affect the anticonvulsant effect of Arthrocen, while pretreatment with flumazenil (0.25 mg/kg), a selective benzodiazepine receptor antagonist, reversed this effect (p < 0.01). Also, Arthrocen treated mice did not affect tonic hindlimb extension in the MES model. The data showed that Arthrocen might produce its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain.

Ameliorative Effects of Ellagic Acid on Maximal Electroshock and Pentylenetetrazole-Induced Seizures in Mice

Background: Epilepsy is a series of disorders in the central nervous system defined by disruption and abnormality in the electrical activity of the brain. The mechanisms of epilepsy occurrence are not fully determined and the current pharmacological therapeutics have low efficacy and are associated with adverse reactions due to narrow therapeutic indices. Ellagic acid has neuroprotective and antioxidant effects and increases the brain’s GABA levels. Objectives: This study was designed to evaluate the effects of ellagic acid on both maximal electroshock and pentylenetetrazole models of acute seizures in mice. Methods: Ellagic acid was administered at the doses of 25, 50, and 100 mg/kg in the two models of seizures. Results: The results showed that ellagic acid was effective at the lowest dose in the maximal electroshock-induced seizure in mice and the duration of hind limb tonic extension (HLTE) was significantly shorter in this group than in the untreated convulsive group. In the pentylenetetrazole convulsion model, ellagic acid significantly increased the latency to convulsion and Straub tail response. The latencies with ellagic acid were longer in groups treated with ellagic acid 25 mg/kg than with ellagic acid 50 and 100 mg/kg. Conclusions: In conclusion, it seems that ellagic acid has anticonvulsant effects in electroshock and pentylenetetrazole models of convulsion but its effects are attenuated or eliminated at higher doses.

Combined anticonvulsant effect of nifedipine and pentazocine in experimentally induced seizures in rats

Background: Epilepsy is one of the common disorders of human with a prevalence of approximately 1% of the total population. Majority of seizures can be controlled with available antiepileptic drugs, about 20% of them still remain resistant to treatment. Recognizing this, there is a need to develop newer antiepileptic drugs with therapeutic potential. Present work is based upon the production of convulsions by maximal electroshock in rats. Evaluation of combined anticonvulsant effect of nifedipine and pentazocine on the duration of convulsion and duration of tonic hind limb extension and recovery in rats.Methods: The study was commenced after obtaining approval from IAEC, Department of Pharmacology, Osmania Medical College, Koti, Hyderabad. All the wistar rats were induced convulsions by Maximal Electro-Shock (MES) method and rats showing tonic hind limb extension response were randomised into four groups (six animals in each group). Group 1 received distilled water, group 2 treated with nifedipine 10mg/kg BW, group 3 treated with pentazocine 30mg/kg BW and group 4 treated with both nifedipine 10mg/kg BW and pentazocine 30mg/kg BW. Drug administered by intraperitoneal route. The data analysed using ANOVA and group means with LSD Post Hoc Test. p‐values &lt;0.05 were considered as significant.Results: When nifedipine and pentazocine were combined, the mean duration of convulsions, tonic hind limb extension and recovery were significantly decreased compared to control, nifedipine and pentazocine.Conclusions: The results obtained in this study provide supporting pharmacological evidence of efficacy, possible potential benefit of combining nifedipine with pentazocine in epilepsy.

Combined Anticonvulsant Effect of Nifedipine and Pentazocine in Experimentally Induced Seizures by Maximal Electro Shock Method in Mice

Objective: The aim of the study was to determine the combined anticonvulsant effect of nifedipine (calcium channel blocker) and pentazocine (opioid analgesic) in experimentally induced seizures by Maximal Electro-Shock (MES) method in mice. Methodology: The swiss albino mice weighing 20-40g of either sex were obtained from National Institute of Nutrition, Hyderabad after obtaining ethical approval. The pretreated mice are subjected to MES stimulation by electro convulsometer with alternate current at intensity required to produce tonic hind limb extension response. The animals showing positive response are divided into four groups (6 animals per group). Group I received distilled water, group II treated with nifidipine (10mg/kg/bw), group III pentazocine (30mg/kg/bw) and group IV combination of nifidipine (10mg/kg/bw) and pentazocine (30mg/kg/bw). Intraperitoneal is the route of administration. The parameters like duration of convulsions, Tonic Hind Limb Extension (THLE) and duration of recovery recorded. P&lt;0.05 was considered as significant and P&lt;0.001 was considered as highly significant. Results: The duration of convulsions, duration of THLE and duration of recovery has been significantly reduced in combination treatment wih nifedipine 10mg/kg and pentazocine 30mg/kg compared to nifedipine 10mg/kg and pentazocine 30mg/kg individually. Conclusion: The results obtained in this study provide supporting pharmacological evidence of efficacy, possible potential benefit of combining nifedipine with pentazocine in the treatment of epilepsy. Keywords: Seizures, Maximal electroshock, Electroconvulsometer, anticonvulsant, Nifedipine, Pentazocine.

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice

Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice

Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice.

Background: There is no universally accepted behavioral scoring to define the early development of pentylenetetrazole (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub-convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling.

Anticonvulsant Activity of Viola tricolor against Seizures Induced by Pentylenetetrazol and Maximal Electroshock in Mice.

Recently, there has been much more interest in the use of medicinal plants in search of novel therapies for human neurodegenerative diseases such as epilepsy. In the present study, we investigated the anticonvulsant effects of Viola tricolor (V. tricolor) on seizure models induced by pentylenetetrazol (PTZ) and maximal electroshock stimulation (MES). Totally, 260 mice were divided into 26 groups (n=10). Thirty minutes after treatment with the hydroalcoholic extract of V. tricolor (VHE 100, 200, and 400 mg/kg) and its ethyl acetate (EAF 50, 100, and 200 mg/kg) and n-butanol (NBF 50, 100, and 200 mg/kg) fractions as well as diazepam (3 mg/kg), seizure was induced by PTZ (100 mg/kg) or by MES (50 Hz, 1 s and 50 mA). Analysis was performed via ANOVA with the Tukey-Kramer post-hoc test using GraphPad Prism 6.01 (La Jolla, CA). The VHE (400 mg/kg) significantly enhanced latency to the first generalized tonic-clonic seizures (GTCs) induced by PTZ in comparison to the control group (P<0.001). All 3 concentrations of the EAF (50, 100, and 200 mg/kg) significantly prolonged the latency of PTZ-induced seizures compared to the control group. Additionally, all the concentrations of the NBF (50, 100, and 200 mg/kg) made a significant increment in GTCs latency induced by PTZ in comparison to the control group. On the other hand, all the concentrations of the VHE, EAF, and NBF significantly reduced the incidence of hind-limb tonic extension (HLTE) induced by MES, when compared to the control group. The present study showed that V. tricolor and its ethyl acetate and n-butanol fractions possessed anticonvulsant effects as confirmed by the prolongation of latency to the first GTCs induced by PTZ and decrement in the incidence of HLTE induced by MES.

Benzyl alcohol suppresses seizures in two different animal models

ABSTRACTIntroduction: We have been exploring the effects of dihydroprogesterone in female amygdala-kindled rats. For intraperitoneal (i.p.) time–response studies, we used a vehicle containing the common solvent, benzyl alcohol (BnOH). The vehicle containing BnOH was also tested alone as a control.Method and Results: Unexpectedly, it was found that the vehicle containing BnOH had clear-cut anti-seizure effects in the kindling model, with an ED50 of 100 mg/kg. In a follow-up study, dose- and time–response studies of i.p. BnOH were done in male mice in the maximal pentylenetetrazol (PTZ) model. BnOH suppressed PTZ seizures in a dose-dependent manner, with an ED50 of 300 mg/kg against hindlimb tonic extension. Effects were fully established at 5-min post injection and lasted for an hour.Conclusion: BnOH is not an inert solvent. It has clear-cut anti-seizure effects against both focal and generalized seizures.

Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana Leaf in Mice

Aim: The study was carried out to determine the anticonvulsant potential of dichloromethane leaf extract of Aspilia africana.&#x0D; Study Design: Three seizure models namely: Pentylenetetrazole (PTZ), strychnine (STC) and maximal electroshock (MES) were used, motor coordination behavior of the animals were also assessed.&#x0D; Place and Duration of Study: The study was carried out between the months of October and November, 2017 at Pharmacology laboratory, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria.&#x0D; Methodology: The powdered leaves of A. africana (2000 g) were extracted with 10 liters of 100% dichloromethane. Doses of 25, 50, 100 and 200 mg/kg were administered to the test animals.&#x0D; Results: The chemical models, STC &amp; PTZ showed 50% &amp; 100% survival respectively. The delayed onset of seizure suggested anti-seizure potential of dichloromethane extract of A. Africana leaf with the maximal latency period of seizure recorded in the 25 mg/kg dose within the following chemical models, this was significant, P = .05 compared to the normal control. The MES method showed that at doses of 25 &amp; 50, 100 mg/kg, the animals were 66.7% &amp; 50% free of hind limb tonic extension (HLTE). Furthermore, there was reduced motor coordination potential at 25 mg/kg by 68.5%, which was significant at the level of, P = .05, compared to healthy control. &#x0D; Conclusion: From the preceding, it can be seen that the dichloromethane leaf extract of A. Africana has antiseizure potential.

Assessment of Morus alba (Mulberry) leaves extract for anti-convulsant property in rats

Background: The mulberry tree, a plant of the family Moraceae and the genus Morus, has been widely cultivated to feed silkworms. Various parts of Morus alba linn used as an Anti-inflammatory, hypoglycemic, cardioprotective, hepatoprotective, free radical scavenging activity and neuroprotective agent. The plant contains flavonoids, moranoline, albanol, morusin coumarine, and stilbene, which have. In this study, anticonvulsant property of Morus alba leaves extract (MAE) was evaluated by using MES and PTZ induced convulsion in rats.Methods: Effects of MAE were evaluated in experimental models of electro convulsions, maximal electro shock (MES) and chemoconvulsion induced by pentylenetetrazole (PTZ) in rats (n=6), which were treated intraperitonially with doses of 100, 200 and 400mg/kg.Results: The duration of tonic hind limb extension (seconds) with MAE in MES induced convulsions at dose of 100, 200, 400 mg/kg is 8.33±1.21, 6.83±1.16 &amp; 3.16±0.98 respectively. In the dose of 400 mg/kg of MAE showed highly significant results by reducing the duration of tonic hind limb extension in MES induced convulsions. And onset of jerky movements (seconds) with MAE in PTZ induced convulsions at dose of 100, 200, 400mg/kg is 157.83±8.99, 195.66±17.02 and 295.50±21.10 respectively. In the dose of 400mg/kg of MAE showed highly significant results by delaying the onset of convulsions.Conclusions: Results indicate that the MAE have anticonvulsant effects in MES induced convulsions and in PTZ induced convulsions.

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 of aqueous extract of Adhatoda vasica leaves by MES model in rats

Background: Epilepsy is the commonest neurological condition affecting people of all ages, race and social class. The present study was taken up to evaluate the anticonvulsant effect of aqueous extract of leaves of Adhatoda vasica in rats. To evaluate the effect of aqueous extract of Adhatoda vasica leaves on maximal electroshock model in albino rats and to compare the effect of aqueous extract of Adhatoda vasica leaves with standard dose of Phenytoin on Maximal electro shock model.Methods: Anticonvulsant activity of aqueous extract of Adhatoda vasica was analysed using MES (Maximal electroshock) model. Phenytoin (25mg/kg) as standard for Maximal electroshock, and two doses of aqueous extract of Adhatoda vasica (100mg/kg and 200mg/kg) were used as test drugs. Parameters observed in MES were abolition of hind limb tonic extension (HLTE) and time taken to regain righting reflex.Results: In MES model, control group showed 0% protection and standard phenytoin group showed 100% protection. Aqueous extract of Adhatoda vasica at 100mg/kg and 200mg/kg showed 33.33% and 50% protection from seizures respectively. The mean duration of time to regain righting reflex was significantly reduced in Adhatoda vasica groups when compared to control group (p &lt;0.001). When groups 100mg/kg and 200mg/kg of Adhatoda vasica were compared for mean difference in the duration of time to regain righting reflex, statistically non-significant results (p &gt;0.05) were obtained.Conclusions: Aqueous extract of leaves of Adhatoda vasica has shown significant anticonvulsant action in MES model.

Phytochemical, antibacterial and anticonvulsant activity of the stem bark of &lt;i&gt;Lannea kerstingii&lt;/i&gt; Engl. &amp; K. Krause (Anacadiaceae)

The stem bark of Lannea kerstingii Engl. & K. Krause was investigated for its phytochemistry, acute toxicity, antibacterial and anticonvulsant activit ies. Standard methods were used to evaluate phytochemistry while antibacterial activity was determined using agar diffusion and broth dilution method s on Staphylococcus aureus , Salmonella typhii , Pseudomonas aeruginosa , Klebsiella pneumonia , Proteus vulgaris , Escherichia coli and Bacillus subtilis . Maximal electroshock-induced seizures test in chicks and pentylenetetrazole-induced seizures test in mice were used to determine the anticonvulsant activity. Phytochemical studies revealed the presence of flavonoids, tannins, carbohydrates steroids and triterpenes. Ethyl acetate and methanol fractions of the stem bark were found to be active against S. aureus , S. typhi , P. aeruginosa , K. pneumoniae , Proteus sp, E. coli , Bacillus subtilis with zone of inhibition ranging from 20-27.5mm and MIC ranging from 6.25mg/mL to 100mg/mL and MBC from 50mg/mL and above. LD 50 was found to be 2154.066 mg/kg. The crude methanol extract of the stem bark afforded dose (150, 300 and 600mg/kg) dependent protection to the laboratory animals against the hind limb tonic extension though not statistically significant (P<0.05) showing the inability of the extract to inhibit seizure discharge within the brainstem seizure substrate. Meanwhile the extract at doses of 300 and 600mg/kg significantly (P<0.05) prolonged the onset of seizure in pentylenetetrazole (PTZ) test showing the potential of this plant in raising seizure threshold in the brain therefore making it beneficial in the treatment of myoclonic and absence seizures. This justifies the use of the plant in treating convulsion. Keywords: Lannea kerstingii ; Anticonvulsant; Phytochemical; Antibacterial; Phytochemistry

Studies on Anticonvulsant Effects of Novel Histamine H3R Antagonists in Electrically and Chemically Induced Seizures in Rats.

A newly developed series of non-imidazole histamine H3 receptor (H3R) antagonists (1–16) was evaluated in vivo for anticonvulsant effects in three different seizure models in Wistar rats. Among the novel H3R antagonists examined, H3R antagonist 4 shortened the duration of tonic hind limb extension (THLE) in a dose-dependent fashion in the maximal electroshock (MES)-induced seizure and offered full protection against pentylenetetrazole (PTZ)-induced generalized tonic-clonic seizure (GTCS), following acute systemic administration (2.5, 5, 10, and 15 mg/kg, i.p.). However, only H3R antagonist 13, without appreciable protective effects in MES- and PTZ-induced seizure, fully protected animals in the strychnine (STR)-induced GTCS following acute systemic pretreatment (10 mg/kg, i.p.). Moreover, the protective effect observed with H3R antagonist 4 in MES-induced seizure was completely abolished when animals were co-administered with the H3R agonist (R)-α-methylhistamine (RAMH, 10 mg/kg, i.p.). However, RAMH failed to abolish the full protection provided by the H3R antagonist 4 in PTZ-induced seizure and H3R antagonist 13 in STR-induced seizure. Furthermore, in vitro antiproliferative effects or possible metabolic interactions could not be observed for compound 4. Additionally, the predictive in silico, as well as in vitro, metabolic stability for the most promising H3R antagonist 4 was assessed. The obtained results show prospective effects of non-imidazole H3R antagonists as innovative antiepileptic drugs (AEDs) for potential single use against epilepsy.

Evaluation of the seizure modifying potential of ondansetron in mice

Background: The aim of the study was to evaluate the seizure modifying potential of Ondansetron in experimental models of seizures in mice.Methods: Mice were treated with three different doses of ondansetron i.p., at 3mg/kg, 6mg/kg and 8mg/kg and control group received normal saline 0.1 ml i.p. for 3 days. On 3rd day, mice were subjected to MES, of different strength half an hour after ondansetron administration and findings were recorded. The minimum threshold current at which tonic hind limb extension occurred was recorded. Each animal was observed for incidence and duration of tonic hind limb extension and the strength of current was noted. In PTZ model, mice were subjected to subconvulsive dose of PTZ 45mg/kg and convulsive dose of PTZ 60mg/kg. The incidence and onset of convulsion at 45 and 60mg/kg dose of PTZ were recorded.Results: Mice receiving ondansetron 3mg/kg, showed significant decrease in duration of tonic hind limb extension at convulsive current strength of 50mA (p&lt;0.001). While group receiving 6mg/kg, showed decrease in seizure threshold. (40mA current strength) Mice receiving 3mg/kg, showed significant increase in onset of seizures (p&lt;0.001) at convulsive 60mg/kg dose of PTZ. While mice receiving 6mg/kg showed decrease in seizure threshold at sub convulsive 45mg/kg dose of PTZ. Group receiving 8mg/kg ondansetron, showed 100% mortality due to convulsions caused by ondansetron.Conclusions: Ondansetron at low therapeutic dose (3mg/kg) has an anticonvulsant action, while it has a proconvulsant action at a high therapeutic dose (6mg/kg). Ondansetron causes convulsions at toxic dose (8mg/kg). So, care should be taken while giving ondansettron in high doses to prevent chemotherapy induced emesis.