Convulsion Model Research Articles

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.

Neurotrophic peptides of сerebrolysin as a basis for anticonvulsant effect of the drug

To study an effect of cerebrolysin on the expression and severity of primary-generalized seizures caused by thiosemicarbazide and to analyze the corresponding molecular mechanisms. The effects of cerebrolysin were studied on the thiosemicarbazide model of convulsions in 144 male rats. Cerebrolysin was introduced intraperitoneally in the dose of 2.5 ml/kg of body mass 5 days a week during 18 days. Cerebrolysin reduces the severity and duration of seizures caused by thiosemicarbazide and increases the survival rate of animals. Cerebrolysin potentiates the anticonvulsant action of gabapentin and sodium valproate. Neurohistological analysis has shown that the thiosemicarbazide model results in the ischemic brain damage. Cerebrolysin substantially minimizes the ischemic injury of neurocytes induced by thiosemicarbazide and contributes to the restoration of brain tissue morphology.

Insignificant anticonvulsant activity of Padina tetrastromatica (Brown macroalgae) in mice

Introduction: Marine macroalgae or seaweeds are found in the coastal region have created a promising significance in the biomedical area, mainly because of their contents of bioactive substances. The objective of the present study was to investigate the anticonvulsant activity of chloroform and ethanol extracts of Padina tetrastromatica (PT), a marine macroalgae (brown algae) in mice. Materials and Methods: The anticonvulsant activity of chloroform and ethanol extracts of PT was studied at 400 and 600 mg/kg, against maximal electroshock (MES) and pentylenetetrazole (PTZ) induced convulsion in mice. The duration of tonic hind limb extension (THLE), latency to onset of clonic convulsions and percent protection was noted in MES and PTZ tests, respectively. Phenytoin (25 mg/kg) and phenobarbitone (20 mg/kg) served as reference standards. Results: The chloroform extract of PT at 600 mg/kg significantly decreased the duration of THLE, while ethanol extract did not alter the duration of THLE in MES model. Further, chloroform and ethanol extracts of PT was found to be ineffective as an anticonvulsant when assessed by PTZ-induced convulsive model, as compared to their respective vehicle-treated groups. Conclusion: From the results of the present study it can be concluded that the chloroform extract of PT at 600 mg/kg showed significant anticonvulsant activity, while other extracts lack anticonvulsant activity in MES and PTZ model. However, further studies are required using different animal models to support these findings.

In silico Design, Synthesis and Pharmacological screening of Quinazolinones as NMDA receptor antagonists for Anticonvulsant activity: Part II

Background : N-methyl-D-Aspartate (NMDA) receptor plays a main role in eliptogenisis and its inhibition has therapeutic significance in development of anticonvulsants. Prioritized quinazolinone molecules were synthesized and then evaluated in vivo by AOT and then for anticonvulsant activity in NMDA induced convulsion model. Method: In silico Screening of prioritized molecule was done by biological activity predictions and partition coefficient predictions (Log P) using PASS server and mol inspiration software respectively. This gave biological activity (BA) score for anticonvulsant activity and predicted Log P values (p Log P). The standard Log P required for anticonvulsant activities being more than 2.00, therefore molecules were also prioritized based on this p Log P criteria. Docking was performed on Vlife MDS 4.3 software. Result: Quinazolinone molecules were prioritized based upon docking score, ADME and BA score, synthesized and pharmacologically screened for anticonvulsant activity. Conclusion: SMMB 1 , SMMB 2 , SMMB 3 showed the prominent anticonvulsant activity as compared with memantine used as standard for in vivo anticonvulsant activity. Key words: Anticovulsant, Mol inspiration, NMDA, PASS, Pre ADMET, Quinazolinone.

Positive effects of ceftriaxone on pentylenetetrazol-induced convulsion model in rats

Aims: Many drugs have been associated with seizures as a side effect. Although they are defined as safe for nervous system. The effect on proconvulsant activity of beta lactam antibiotics have been also reported. We aimed to investigate whether ceftriaxone has an anticonvulsant effect on PTZ-induced seizures in rats. Materials and Methods: 36 male Sprague-Dawley rats, 18 of them for EEG recording and 18 of them are for behavioral studies, were randomly divided in two groups: group A for EEG recordings and group B for behavioral assesment. About 70 mg/kg PTZ was used for behavioral studies after Ceftriaxone administiration. About 35 mg/kg PTZ were used for EEG recording after ceftriaxone administiration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale, first myoclonic jerk onset time, spike percentages, brain MDA and SOD levels were evaluated between the groups. Results: First myoclonic jerk onset time was significantly shorter in saline group than both 200 and 400 mg/kg ceftriaxone groups (p < 0.05). Racine's convulsion scale was significantly lower in 200 and 400 mg/kg ceftriaxone groups than saline group (p < 0.01, p < 0.0001). Both of two ceftriaxone groups have lower spike percentages than the saline group (p < 0.05). Significantly lower MDA levels and higher SOD activity were determined in 200 mg/kg ceftriaxone group compared with the saline group (p < 0.05). Conclusion: Our study demonstrated that ceftriaxone has protective effects on PTZ-induced convulsions and on oxidative damage associated with PTZ.

An enhanced home cage modulates hypothalamic CRH-ir labeling in juvenile rats, with and without sub-threshold febrile convulsions.

Pre and postnatal environments can have a profound impact on offspring development. This is especially true when considering the origin of neurological diseases, including epilepsy, a relatively common and chronic neurological condition, affecting 1-2% of the population. Previously, we have used maternal stress and an enhanced home cage (EHC) in an effort to identify potential factors in the early environment that may increase the risk for experiencing seizures. First, pregnant Long-Evans rats were exposed to a predator stress (PS). Then, at birth, litters were divided into standard cage (SC) and EHC groups until postnatal Day 14 (PD14) when a model of febrile convulsions was used to determine convulsion susceptibility of the various groups. Twenty-four hours later, pup brains were processed for immunohistochemical detection of corticotrophic releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus. Analysis of CRH immunoreactive (-ir) patterns revealed a buffering of CRH-ir in EHC reared offspring. Further, experiencing convulsions led to decreased CRH-ir. Our results support the concept that postnatal environmental influences affect neonatal programming and neurodevelopment of processes that could underlie seizure susceptibility, and that these effects can be modulated by EHC conditions.

Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives

A new series of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ)-evoked convulsion model and antidepressant activity in the forced swimming test (FST) model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q) showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ−/−) subjected to intrahippocampal microinjection of pilocarpine. PI3Kγ−/− mice presented a more severe status epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or pharmacological blockade of PI3Kγ enhanced the release of glutamate and the cytosolic calcium concentration induced by KCl. There was an enhanced neuronal death and a decrease in the doublecortin positive cells in the dentate gyrus of PI3Kγ−/− animals after the induction of SE. Levels of BDNF were significantly increased in the hippocampus of WT and PI3Kγ−/− mice, although in the prefrontal cortex, only PI3Kγ−/− animals showed significant increase in the levels of this neurotrophic factor. Pilocarpine increased hippocampal microglial immunolabeling in both groups, albeit in the prelimbic, medial and motor regions of the prefrontal cortex this increase was observed only in PI3Kγ−/− mice. Regarding the levels of inflammatory mediators, pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and PI3Kγ−/− animals and in the prefrontal cortex of PI3Kγ−/− animals 24h after the stimulus. Levels of TNFα were enhanced in the hippocampus and prefrontal cortex of only PI3Kγ−/− mice at this time point. On the other hand, PI3Kγ deletion impaired the increase in IL-10 in the hippocampus induced by pilocarpine. In conclusion, the lack of PI3Kγ revealed a deleterious effect in an animal model of convulsions induced by pilocarpine, suggesting that this enzyme may play a protective role in seizures and pathological outcomes associated with this condition.

Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone.

A new series of quinazoline analogues was designed and synthesized to get the target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization.

Ichnocarpus frutescens Ameliorates Experimentally Induced Convulsion in Rats.

The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF (100, 200, and 400 mg/kg, p.o.) was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of γ-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF (200–400 mg/kg, p.o.) protected the animals in all the behavioral models used. Pretreatment of MEIF (200–400 mg/kg, p.o.) and diazepam (1.0 mg/kg, i.p.) to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin (50 mg/kg, i.p.) reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens.

CNS activity of leaves extract of Calotropis gigantea

ObjectiveTo study central nervous system activity of ethanolic extract of leaves of Calotropis gigantea (C. gigantea) (Asclepiadaceae), such as anticonvulsant, sedative and muscle relaxation activity. MethodsThe ethanolic extract of C. gigantea administered orally in experimental animals at different doses 100, 200 and 500 mg/kg body weight. The anticonvulsant properties were studied on maximal electroshock test and strychnine-induced convulsions model. Sedative property studied using actophotometer and skeletal muscle relaxant property studied using rota rod. ResultsThis extract protected rats against maximal electroshock induced seizures, but had no or a moderate effect only against strychnine-induced seizures. Locomotor activity in mice found to be decreased and motor coordination was also decreased. The acute toxicity study revealed safely of the extract up to a dose of 2 000 mg/kg. ConclusionsWith these effects, the leaves of C. gigantea possess anticonvulsant sedative and muscle relaxant effect that might explain its use as a traditional medicine.

Albumin nanoparticles for the delivery of gabapentin: Preparation, characterization and pharmacodynamic studies

The study was aimed to prepare and evaluate gabapentin loaded albumin nanoparticles and to find out their effectiveness in treating epilepsy. Albumin nanoparticles of gabapentin were prepared by pH-coacervation method. The drug was administered into animals as free drug, gabapentin bound with nanoparticles, and gabapentin bound with nanoparticles coated with polysorbate 80. The polysorbate 80 coated nanoparticles increased the gabapentin concentration in the brain about 3 fold in comparison with the free drug. Moreover, the polysorbate 80 coated nanoparticles significantly reduced the duration of all phases of convulsion in both maximal electroshock induced and pentylenetetrazole induced convulsion models in comparison with free drug and drug bound with nanoparticle formulations, which indicates the ability of polysorbate 80 coated nanoparticles to enhance the gabapentin concentration in the brain.

Altered expression of hypoxia‐Inducible factor‐1α participates in the epileptogenesis in animal models

Although epilepsy is a common neurological disorder, its mechanism(s) are still not completely understood. Hypoxia can lead to neuronal cell death and angiogenesis, and the same mechanisms were also found in epilepsy. Hypoxia-inducible factor-1α (HIF-1α) is an important transcription protein that regulates gene expression in the brain and other tissues in response to decreases in oxygen availability. However, little is known regarding the expression of HIF-1α in the epileptic brain and whether HIF-1α interventions affect the epileptic process. The aims of this study are to investigate the expression profile of HIF-1α in rat models and to explore the role of HIF-1α in epilepsy. We performed Western blots and immunofluorescence in a lithium-pilocarpine rat epilepsy model. To determine the role of HIF-1α in epilepsy, we used the HIF-1α agonist DMOG and inhibitor KC7F2 to detect changes in the animal behavior in pentylenetetrazole (PTZ) and lithium-pilocarpine epilepsy models. The expression of HIF-1α was significantly increased after pilocarpine-induced status epilepticus. DMOG significantly prolonged the latent period in the PTZ kindling model and decreased the rate of spontaneous recurrent seizures during the chronic stage in the lithium-pilocarpine model. Conversely, the inhibitor KC7F2 produced an opposite behavioral change. Interestingly, both KC7F2 and DMOG had no effect on the acute stage of pilocarpine model and PTZ convulsive model. Our study suggests that upregulated HIF-1α may be involved in the process of epileptogenesis but not in the acute stage of epilepsy. The modulation of HIF-1α may offer a novel therapeutic target in epilepsy.

Valproate-Induced Liver Injury: Modulation by the Omega-3 Fatty Acid DHA Proposes a Novel Anticonvulsant Regimen

BackgroundThe polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA.Methods and ResultsVPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor necrosis factor-alpha (TNFα) levels, as well as myeloperoxidase (MPO) activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250 mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides, TNFα, and MPO activity, while raising serum albumin and hepatic GSH levels. DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly increased the latency in convulsion evoked by VPA, beyond their individual responses. Lastly, pharmacokinetic studies revealed that joint DHA administration did not alter serum VPA concentrations.ConclusionsDHA substantially ameliorated liver injury induced by VPA, while also markedly boosted its pharmacologic effects. DHA manipulated definite cellular machinery to curb liver oxidative stress and inflammation, without affecting VPA plasma levels. Collectively, these protective and synergy profiles for DHA propose a superior VPA-drug combination regimen.

Repeated febrile convulsions impair hippocampal neurons and cause synaptic damage in immature rats: neuroprotective effect of fructose-1,6-diphosphate.

Fructose-1,6-diphosphate is a metabolic intermediate that promotes cell metabolism. We hypothesize that fructose-1,6-diphosphate can protect against neuronal damage induced by febrile convulsions. Hot-water bathing was used to establish a repetitive febrile convulsion model in rats aged 21 days, equivalent to 3–5 years in humans. Ninety minutes before each seizure induction, rats received an intraperitoneal injection of low- or high-dose fructose-1,6-diphosphate (500 or 1,000 mg/kg, respectively). Low- and high-dose fructose-1,6-diphosphate prolonged the latency and shortened the duration of seizures. Furthermore, high-dose fructose-1,6-diphosphate effectively reduced seizure severity. Transmission electron microscopy revealed that 24 hours after the last seizure, high-dose fructose-1,6-diphosphate reduced mitochondrial swelling, rough endoplasmic reticulum degranulation, Golgi dilation and synaptic cleft size, and increased synaptic active zone length, postsynaptic density thickness, and synaptic interface curvature in the hippocampal CA1 area. The present findings suggest that fructose-1,6-diphosphate is a neuroprotectant against hippocampal neuron and synapse damage induced by repeated febrile convulsion in immature rats.

Investigation of the effects of magnetic field exposure on febrile seizure latency, seizure duration, and electroencephalographic recordings in a rat febrile convulsion model

To investigate the effects of a magnetic field (MF) on febrile seizure latency, seizure duration, and electroencephalographic (EEG) recordings in a rat febrile convulsion model. Thirty-six rats were randomly allocated into 1 of 6 groups: sham group (S), febrile convulsion (FC) group without MF exposure, MF group without FC, group exposed to MF before FC (MF + FC), group exposed to MF after FC (FC + MF), and group exposed to MF before and after FC (MF + FC + MF). The rectal temperature after febrile seizure induction, seizure latency, seizure duration, and EEG recordings were recorded for all animals. Repeated hyperthermic exposure decreased the seizure latency and duration. The effect of the MF was more prominent on seizure duration than on latencies. MF exposure for 10 or 12 days increased seizure latency. MF exposure increased the pathologic theta and delta waves and decreased the beta waves, which are frequently seen in awake animals. Our results suggest that MF exposure has a negative effect on brain waves, and this effect becomes more evident with prolonged exposure. On the other hand, MF exposure significantly decreased the convulsion durations.

Anticonvulsant activity of Morusin isolated from Morus alba: Modulation of GABA receptor

Aim of the studyEpilepsy is a complex neurological disorder affecting 50 million of world's total population. Number of medicinal plants has been used to treat the convulsion. In ancient time Morus alba was used to treat epilepsy and mental illness. In Chinese medicine also M. alba is used as neuroprotective herbs. The present study was designed to explore the effect of Morusin, a flavonoid glycoside isolated from M. alba as anticonvulsant activity along with biochemical mechanism. Materials and methodsMorusin was isolated from M. alba and acute toxicity study was determined. Anticonvulsant activity of Morusin (5 and 10mg/kg, i.p.) was studied by using isoniazid (INH) and maximal electroshock (MES)-induced convulsion models; diazepam (5mg/kg) and phenytoin (20mg/kg) were used as standards, respectively. Biochemical mechanism was investigated by estimating the GABA level in brain. ResultsThe median lethal dose (LD50) of Morusin was found up to 20mg/kg. Treatment with Morusin (5 and 10mg/kg) delayed onset of convulsion and tonic hind limb extension along with duration of tonic-clonic convulsions as well as it significantly reduced mortality in INH and MES-induced convulsion. Rats treated with Morusin (5 and 10mg/kg) significantly increased level of brain GABA at both doses. ConclusionThe findings of current study provide pharmacological credibility to anticonvulsant activity of Morusin. The protection against the convulsions and restoration of GABA level give a suggestion to its probable mechanism of action.

Limbic system activation is affected by prenatal predator exposure and postnatal environmental enrichment and further moderated by dam and sex

Epilepsy is a relatively common and chronic neurological condition, affecting 1–2% of the population. However, understanding of the underlying pathophysiology remains incomplete. To identify potential factors in the early environment that may increase the risk for experiencing seizures, maternal stress and environmental enrichment (EE) were utilized. Pregnant Long-Evans rats were exposed to an ethologically relevant predator stress (PS) and maternal glucocorticoid (GC) response was assessed across the exposure period. At birth, litters were divided into standard care (SC) and EE groups until postnatal day 14 (PD14) when a model of febrile convulsions was used to determine seizure susceptibility of the various groups. Pup brains were then processed for immunohistochemical detection of FosB from several structures in the limbic system as a measure of neuronal activation. Maternal PS-induced GC levels were elevated early in the exposure period, and pup birth weights, in both sexes, were lower in litters from dams exposed to PS. Seizure scores at PD14 were highly individualized and litter dependent, suggesting a dam-dependent and variable effect of controlled pre- and postnatal environmental factors. Further, analysis of FosB-immunoreactive (-ir) patterns revealed an activity dependent distribution, reflecting individual seizure susceptibility. EE had a varying effect on FosB-ir that was dependent on region. In the hippocampus FosB-ir levels were greater in the EE groups while extra-hippocampal regions showed lower levels of FosB-ir. Our results support the concept that pre- and postnatal environmental influences affect fetal programming and neurodevelopment of processes that could underlie seizure susceptibility, but that the magnitude of these effects appears to be dam- or litter-dependent.

Anxiolytic and anticonvulsant activity of alcoholic extract of heart wood of Cedrus deodara roxb. in rodents.

The objective of the present study was to evaluate the anxiolytic and anticonvulsant activity of the alcoholic extract of heart wood of Cedrus deodara(ALCD). 50, 100 and 200 mg/kg of ALCD were tested for its anxiolytic and anticonvulsant activity. Anxiolytic activity was tested by exposing mice to unfamiliar aversion in different methods like elevated plus maze model, light-dark model and actophotometer. The results suggest that ALCD reduced the aversion fear and produced anxiolytic activity in a dose dependent manner. Pentylenetetrazole (PTZ) induced convulsions and maximal electro shock (MES) induced convulsions models in mice were used for assessment of its anticonvulsant activity. 100 and 200 mg/kg of ALCD increased the onset of clonus and tonic seizures in PTZ induced convulsions model and decreased the duration of tonic extensor phase in MES induced convulsions model and also increased the percentage protection in PTZ and MES induced convulsions. Effect of ALCD (30 and 100 mg/kg) on gamma aminobutyric acid (GABA) levels of brain also studied. Estimation of GABA in rat brain after administration of ALCD showed significant modulation of GABA levels. In conclusion these observations suggest that 100 and 200 mg/kg doses of ALCD exhibit anxiolytic and anticonvulsant activity. Key words: Cedrus deodara, anxiolytic, anticonvulsant, gamma aminobutyric acidestimation.

Synthesis and Biological Evaluation of Some [1,2,4]Triazolo[4,3-a]quinoxaline Derivatives as Novel Anticonvulsant Agents

2-([1,2,4]Triazolo[4,3-a]quinoxalin-4-ylthio)acetic acid hydrazide (10) was used as a precursor for the syntheses of novel quinoxaline derivatives with potential anticonvulsant properties. The newly synthesized compounds have been characterized by IR, 1H NMR, and mass spectral data followed by elemental analysis. The anticonvulsant evaluation was carried out for eleven of the synthesized compounds using metrazol induced convulsions model and phenobarbitone sodium as a standard. Among this set of tested compounds, two of them (14, and 15b) showed the best anticonvulsant activities.