Sodium Phenobarbitone Research Articles

Screening of Neuropharmacological Activities of Naringi crenulata (Roxb.) Nicolson Leaves

Purpose: Although the global prevalence of psychological disorders is increasing continually, the efficacies of therapeutic strategies are still very limited. Oxidative stress has been implicated in the pathogenesis of psychiatric disorders and substances possessing antioxidant activity can alleviate the mentioned conditions. Therefore, we hypothesized that Naringi crenulata (Roxb.) Nicolson leaves, a medicinal plant claimed for nerve tonic, also possess neuropharmacological activities which provide an advantage for psychiatric disorders.
 Methods: The present study was carried out to perform neuropharmacological screenings methods on sedatives and hypnotics (Phenobarbitone sodium-induced sleep latency and sleep time and Motor coordination activity), anxiolytics (elevated plus maze and open field test), anti-depressants (forced swim test and L-dopa induced hyperactive aggressive behaviour in mice) and anticonvulsants activities (PTZ and MES induced convulsions) in Swiss Albino mice and Sprague Dawley rats.
 Results: The methanolic extract of a higher dose of Phenobarbitone sodium in Naringi crenulata induced sleep latency and sleep time significant results. The extracts of Naringi crenulate showed a significant dose-dependent increase in muscle relaxation in motor coordination activity. In the experiment of PTZ-induced convulsions, the latency of seizures was prolonged by the extracts in a dose-dependent manner. Even in MES-induced convulsion, the results were extremely significant for the 400mg/kg of MENC. The depressant effect was observed to be significant to the extracts of the herb in the Open Field test and also for the Elevated Plus Maze apparatus. In the Forced Swim Test, MENC (400 mg/kg) significantly lengthened the time spent immobile (p <0.01), indicating a CNS depressive impact. Lastly in L-dopa-induced hyperactive aggressive behaviour in mice, results suggest that NC has antidepressant efficacy due to its influence on the serotonergic, noradrenergic, and dopaminergic systems.
 Conclusion: The methanolic extract of Naringi crenulata (Roxb.) Nicolson leaves showed significant neuroprotective activity. So, the extracts of Naringi crenulata can be used for the treatment of a wide variety of neurological ailments in humans.

English

Picrasma javanica Blume. is locally known as Nilghanta. Traditionally, the plant is used as an anti-pyretic. The aim of this study was to determine the biological properties of P. javanica leaf extract. The writhing test and tail flick response were determined to assess peripheral and central analgesic activities, respectively. Castor oil was fed orally to induce diarrhea in the test animals. Paw edema method was followed to determine the anti-inflammatory potential. Neuropharmacological property of the extract was determined using phenobarbitone sodium. 400 mg/kg body weight dose of P. javanica leaf extract inhibited 70.41% writhing which was comparable to that of diclofenac sodium (75.71% inhibition). The extract also reduced diarrheal feces by 63.10% and carrageenan induced rat paw edema by 91.49% at the same dose. On the other hand, P. javanica extract increased the duration of phenobarbitone sodium-induced sleep. P. javanica leaf extract is a suitable future candidate for phytochemical screening. Key words: Acetic acid, writhing, castor oil, paw edema, carrageenan.

In vivo screening and toxicity studies of indolinone incorporated thiosemicarbazone, thiazole and piperidinosulfonyl moieties as anticonvulsant agents

Based on the biological importance of the thiazole nucleus, we decided to prepare and evaluate the biological activity of some new isatin derivatives containing thiazole moiety. The 5-(piperidin-1-ylsulfonyl)indoline-2,3-dione (1) was prepared and used as a starting material in the synthesis of many isatin derivatives for anticonvulsant evaluation. All the newly synthesized thiazlidino/thiosemicarbazide-indolin-2-one derivatives screened in vivo for their anticonvulsant activity against pentylenetetrazole-induced convulsions in mice. The results were compared with phenobarbitone sodium as a standard anticonvulsant drug. Most of the tested compounds exhibited anticonvulsant activity with relative potency ranging from 0.02 to 0.2 in comparison to standard drug phenobarbitone. The most active compounds 3, 6a, 6c and 8, were exposed to further investigations in rats to evaluate the effect of most active derivatives on the haematological, liver, kidney functions as well as histopathological studies of the liver and kidney tissues. Finally, the most potent compounds 3, 6a, 6c and 8 observed good toxic properties for both liver and kidney function with mild variability changes on RBCs, WBCs, Platelets, Hb, AST, ALT, and creatinine level, as well as kidney and liver tissue and these good results obtained rather than used low dose from phenobarbitone.

Effect Of Variation Barbiturate (Sodium Phenobarbitone) Lethal Dose On Calliphoridae Larvae Length To Rat (Rattus Norvegicus) Carcasses Wistar Strain

Background: Determining the time of death (post-mortem interval) is very important in forensic investigations. Blowflies growth is the main and most accurate indicators time of death to estimation PMI. The growth of flies can be affected by various factors including climate, geography, and medicines contained in the body. The aim of this study was to examine the effect of giving variations barbiturate (sodium phenobarbitone) lethal dose to the length of Calliphoridae larvae to predicting PMI.
 Methods: This study is an experimental study with post-test only control group design, the data were analyzed using multivariate linear regression analysis test. This study consisted of 1 control group (neck dislocation) and 3 control groups of phenobarbital (750 mg/kgBW, 900 mg/kgBW and 1050 mg/kgBW). All group are put into a cage containing Chrysomya sp. The measurements of larva length are carried out every 12 hours by taking the largest larvae size in each rat in the study group.
 Result: The results shown that phenobarbital was the most influential factor in the larval length of Chrysomya sp. (p <0.05, R = -0.64) compared to temperature and humidity. Mann Whitney test results (p <0.05) shown the significant difference in Chrysomya sp. larvae length in each study group.
 Conclusions: Variation lethal dosage of barbiturates (sodium phenobarbital) affects the growth of Chrysomya sp larvae length.

Drug Interaction analysis-Nigella sativa L.seed (Black Cumin) ethanolicextract on antiseizure activity of Phenobarbitone sodium

Background: Multidisciplinary therapy is gaining popularity and drug herb interactions is one of the biggest risk factor contributing to therapeutic failures or toxicities. Apart from analysis of one of such Drug-Herb combinations, this work also aims at emphasizing need for ethnopharmacovigilance practices.
 Aims and Objectives: Herb-Drug Interaction analysis between Nigella sativa seed ethanolic extract and Phenobarbitone sodium in maximal electroshock seizure in Swiss albino mice with a modified isobolographic analysis.
 Materials and Methods: Experiment model was Maximal electroshock seizure in Swiss albino mice. Dose ratios of the combination tested were NsEE: Phenobarbitone; 3:1(NsEE75%: Pbt25%), 1:1, 1:3. Analysis was done with modified isobolographic analysis.
 Results: Nigella sativa seed ethanolic extract exhibit synergistic interaction with Phenobarbitone sodium at 1:1 and 1:3 dose ratios and antagonistic interaction at 3:1 combination. The parameter measured was Hind limb tonic extensor phase in maximal electroshock seizure test in Swiss albino mice.
 Conclusion: The study showed that interaction profile of Nigella sativa extract-phenobarbitone combination is dose dependent and requires well designed posological studies in epileptic patients to formulate dose adjustment guidelines for multidisciplinary therapy with the herb and Phenobarbitone, also to avoid food drug interactions.

Estimation of liver enzymes in patients taking antiepileptic drugs in a tertiary care center: A cross-sectional study

Background: A number of antiepileptic drugs (AEDs) are used in the management of epilepsy. Almost all AEDs undergo hepatic biotransformation. Since drugs contribute a major part in causing liver injury, there is a need for identifying it. This study was designed to estimate the prevalence of liver enzyme elevation among patients treated with AEDs. Aims and Objectives: This study aims to estimate the prevalence of liver enzyme elevation and/or liver dysfunction in patients receiving AEDs. Materials and Methods: This cross-sectional descriptive study was conducted in the Department of Neurology, Tirunelveli Medical College Hospital for a period of 6 months. About 150 patients on AEDs, who met the inclusion and exclusion criteria, participated in the study. Demographic data, disease history, drug history, and history of any adverse drug reactions were recorded. Venous blood sample was collected to analyze complete blood count, serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Results: Among 150 patients, 86 were male and 64 were female. Of these, 109 patients were on monotherapy with carbamazepine, sodium valproate, phenytoin, or phenobarbitone and rest 41 were on combination therapy. Serum AST levels were elevated in four patients treated with sodium valproate, phenytoin, or phenobarbitone as monotherapy, whereas ALT enzyme elevation was observed only in one male patient who was on sodium valproate as monotherapy. Serum alkaline phosphatase (ALP) was elevated in 14 patients and decreased in three patients. Conclusion: The magnitude of elevation in serum AST, ALT, and ALP levels with AEDs was found to be statistically insignificant. As such, there was no liver dysfunction in patients receiving AEDs as monotherapy or polytherapy.

Investigation of biological activities of the flowers of Lagerstroemia speciosa, the Jarul flower of Bangladesh

BackgroundLagerstroemia speciosa (L.) Pers. (Family: Lythraceae) is used in traditional medicine in the treatment of diarrhea, diabetes and other diseases. The study was performed to conduct antioxidant, cytotoxic, thrombolytic, membrane stabilizing, antimicrobial, peripheral and central analgesic and hypoglycemic activity assays and phenobarbitone sodium–induced sleeping time test using crude methanol extract of flowers of L. speciosa and its different partitionates.MethodThe antioxidant potential was evaluated by determining the ability of the samples to scavenge 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical. The cytotoxic potential was examined following the procedures of brine shrimp lethality bioassay. Thrombolytic potential was assayed using streptokinase as standard. The samples were subjected to membrane stabilizing activity assay under heat induced condition. Antimicrobial potential was observed by disc diffusion method. The ability of the extract to inhibit writhing induced by acetic acid was determined in peripheral analgesic activity assay. The extract was also tested for central analgesic and hypoglycemic activities by tail flicking and tail tipping methods in Swiss albino mice model, respectively. CNS depressant activity was evaluated by an assay in which sleep was induced in mice using phenobarbitone sodium.ResultsThe chloroform soluble fraction of L. speciosa extract demonstrated the highest antioxidant activity (IC50 = 4.20 ± 0.41 μg/ml) while the most prominent cytotoxic potency was showed by hexane soluble fraction (LC50 = 2.00 ± 0.31 μg/ml). Among the test samples, the carbon tetrachloride soluble fraction induced clot lysis (64.80 ± 0.27%) and prevented heat induced haemolysis (41.90 ± 0.10%) to the maximum extent. The largest zone of inhibition (19.0 mm) against Staphylococcus aureus, was also observed for the same fraction. In peripheral analgesic activity assay, 16.68% inhibition of writhing was documented for the L. speciosa extract (400 mg/kg body weight dose). The extract (400 mg/kg dose) also reduced blood sugar level by 56.12% after three hours of administration of glucose solution. In CNS depressant activity assay, mice of the sample group slept for shorter period of time compared to control group.ConclusionsFrom our investigation, it can be suggested that, the extract should be further studied for possible phytochemicals responsible for the observed biological activities.

Comparision of antiepileptic property of various parts of datura

Epilepsy is the most common of the neurological conditions that are widely affecting most of the population around the world. It is a condition on its own and a symptom of other neurological conditions too. It affects almost one per cent of the human population. Many synthetic drugs are produced to treat epilepsy effectively in various mechanisms. Few of them are Barbiturates like phenobarbitone and barbital sodium, hydantoin derivatives like Phenytoin, Sedatives and azepam derivatives like Diazepam etc. Many drugs treat epilepsy but are not devoid of side effects as discussed. So herbs are supporting the system of medicine to treat epilepsy but don't have side effects and adverse effects. There are a lot of herbs that are used to treat the disease on among them is Datura stromonium. In this work, the comparison between the antiepileptic property of the different parts of Datura was investigated, which included Flowers, Leaves, Stems and Fruits. The activity was investigated in electrical shock method to induce epilepsy. The brain enzymes were used as estimating parameters. Overall, the flowers showed very less activity compared to stems followed by fruits, and leaves of the plant Datura stramonium showed the highest activity.

A PROSPECTIVE STUDY OF DRUG UTILIZATION PATTERN OF ANTI-EPILEPTIC DRUGS AND THEIR ADVERSE EFFECTS IN A TERTIARY CARE HOSPITAL

Objective: Epilepsy or seizure disorder is a common neurologic disorder in the pediatric age group and occurs with a frequency of 4-6 cases per thousand children. Epilepsy, particularly childhood epilepsy, remains a challenge to treat. The management of epilepsy is primarily based on theuse of anti-epileptic drugs. Surgery and diet therapy are the other modes of treating childhood seizures. To get an insight into the utilization pattern of anti-epileptic drugs (AEDs) used in pediatric seizures.Methods: This prospective, longitudinal study was conducted for a period of 8months in Paediatric Neurology Department of a tertiary care teaching hospital. The data collected from 50 children at the end of the study, were compiled in a specially designed data form and were analyzed.Results: The distribution of paediatric seizures was found to be high in male children (62%) and in the age group of 2 to 5 y (46%). The majority of the children (70%) were diagnosed with Generalized Tonic-clonic seizures. Sodium valproate was the commonly prescribed AED in all forms of seizures followed by Carbamazepine (18%), Phenobarbitone (4%) and Phenytoin Sodium (4%). AEDs were mostly prescribed as monotherapy (82%). Adverse reactions noted during this study was minimal (12%).Conclusion: Sodium valproate, a conventional AED still remains the commonly prescribed AED for all types of seizures in children aged 2 to 16 y and also was found to be effective and safe.

Macrolide antibiotics differentially influence human HepG2 cytotoxicity and modulate intrinsic/extrinsic apoptotic pathways in rat hepatocellular carcinoma model.

This study was designed to examine the potential antitumor effect of some macrolides: clarithromycin, azithromycin, and erythromycin on chemically induced hepatocellular carcinoma (HCC) in rats and on human hepatoma cells (HepG2) as well. The possible underlying antiapoptotic mechanisms were investigated. Antiproliferative activity was assessed in HepG2 using Sulforhodamine-B staining method. In vivo, HCC was induced in rats by initiation-selection-promotion protocol using diethylnitrosamine (200mg/kg, single i.p. injection)/2-acetylaminofluorene (0.03% w/w supplemented-diet for 2weeks)/carbon tetrachloride (2ml/kg diluted in corn oil 1:1, single intra-gastric dose)/phenobarbitone sodium (0.05% w/w supplemented-diet for 28weeks). Macrolides were administered once daily starting from the 3rd week until the 17th week at a dose of 100mg/kg in the current 33-week study period. Clarithromycin showed a higher efficacy in the suppression of HepG2 proliferation with lower IC50 value than doxorubicin. In vivo, chemically-induced HCC rat model proved that clarithromycin suppressed HCC via induction of apoptosis through up-regulation of both extrinsic/intrinsic apoptotic pathways' proteins (TNFR1, cleaved caspase-3, and Bax with an increased Bax/Bcl-2 ratio) along with MMP-9 normalization. Similarly, azithromycin demonstrated antitumorigenic effect through both apoptotic pathways, however, to a lesser extent compared to clarithromycin. Moreover, azithromycin suppressed the proliferation of HepG2, however, at a higher IC50 than doxorubicin. Surprisingly, erythromycin increased HepG2 proliferation in vitro, along with worsened tumorigenic effect of the carcinogenic agents in the in vivo study with ineffective apoptotic outcome. Some macrolides represent potential antitumor agents; however, this evident anticancer activity is an individual effect rather than a group effect and involves modulation of both intrinsic and extrinsic apoptotic pathways.

Modulation of Intrinsic and Extrinsic Apoptotic Pathways by Macrolide Antibiotics in Chemically‐Induced Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC) is one of the most common solid malignancies and a leading cause of cancer‐related deaths. Macrolide antibiotics demonstrated beneficial effects in several pathological conditions however; their therapeutic potential in cancer is not fully elucidated. The current study aimed to investigate the individual anti‐tumor effect of some macrolide antibiotics in chemically‐induced HCC. HCC was induced in rats by initiation‐selection‐promotion protocol using diethylnitrosamine (200 mg/kg, single i.p. injection)/2‐acetylaminofluorene (2‐AAF) (0.03%w/w supplemented diet for 2 weeks/carbon tetrachloride (2ml/kg diluted in corn oil 1:1, single intra‐gastric dose)/phenobarbitone sodium (0.05%w/w supplemented diet for 28 weeks). Macrolides were administered once daily from the beginning of the 3rd week until week 17 at a dose of 100mg/kg and study was terminated on week 32. Current data proved that clarithromycin suppresses HCC via induction of apoptosis through up‐regulation of both extrinsic and intrinsic apoptotic pathways proteins (TNF‐α, TNFR1, cytochrome‐c, caspase‐3, and Bax with increased Bax/Bcl2 ratio). Similarly azithromycin reduced the tumorgenic effect of the former carcinogenic agents, however to a lesser extent compared to clarithromycin. Surprisingly, erythromycin worsened the tumorgenic effect of the carcinogenic agents used in the current model with insignificant apoptotic outcome. It is concluded that the anticancer potential of some macrolide antibiotics is an individual effect rather than a group effect and the current detected anti‐tumor mechanism involved the activation of both intrinsic and extrinsic apoptotic pathways.

Pattern of Drug Utilisation in Neonatal Intensive Care Unit in a Tertiary Care Hospital

Background: Every year millions of babies are born and a large proportion of them are admitted to the neonatal ward for various indications. Neonates particularly preterm and very preterm neonates are the most vulnerable population. There is paucity of information to guide rational prescribing in children and newborns. Objectives: The objective of this study was to determine the patterns of drug use in newborns in tertiary care NICU, VIMS, Bellary, Southern India. Materials and Methods: Data from 100 Case records of newborns admitted in NICU from Jan 2013 - June 2013 was collected. Information regarding gender, gestational age, birthweight, length of hospital stay, survival status at discharge, and details of all drugs used was collected in the prestructured proforma and subjected to statstical analysis. Results: Among 100 study subjects 57% were females and 43% were males. Only 51% of them completed term. Majority of them were admitted with Perinatal asphyxia complicated by HIE (48%). The most common drugs used were Ceftriaxone(75%) and Amikacin(75%), Phenobarbitone sodium(39%), VitaminK(19%) and Aminophylline(11%).73% of newborns were recovered. The relation between gestational age, birth weight, indications and the type of drugs used was found to be statistically significant. Conclusion: Ceftriaxone and Amikacin are most commonly used drugs. Appropriate care was given to all the neonates to improve the outcome.

Membrane stabilizing, thrombolytic, analgesic, anti-diarrheal and CNS activities of Polyalthia longifolia (Sonn.)

Different fractions of Polialthia longifolia (Sonn.) bark were evaluated for membrane stabilizing, thrombolytic, analgesic, anti-diarrheal and CNS de-pressant activities upon oral administration at 200 and 400 mg/kg body weight. The membrane stabilizing activity was assessed by heat and hypo-tonic solution. Carbon tetrachloride fraction of methanol extract of P. longi-folia bark demonstrated strong membrane stabilizing activity, while the crude methanol extract demonstrated mild to moderate thrombolytic activi-ty in human blood specimen. The analgesic activity was assessed by tail im-mersion and formalin-induced pain method in Swiss-albino mice. The crude methanol extract of P. longifolia bark exhibited significant peripheral and central analgesic activity, since inhibited chemical induced writhing at 200 mg/kg and increased tail flick latency time both at 200 and 400 mg/kg. The anti-diarrheal activity of the bark extract was assessed by using castor oil induced diarrhea in mice however significant anti-diarrheal activity was not revealed. The CNS inhibitory activity of the methanol extract was assessed in Swiss albino mice where it reduced phenobarbitone sodium induced sleep-ing time at 400 mg/kg.

Psychopharmacological studies of Mammea africana stem bark extract

Herbal medicine is an integral part of the health care system in most developed and developing countries of the world. Objective: The stem bark of Mammea africana used traditionally in the treatment of mental disorders was evaluated for depressive effect on the central nervous system (CNS). Materials and Method: The stem bark extract was investigated for depressive activity in the open field, force swimming and tail suspension tests as well as its anticonvulsant potential against pentylene tetrazol and aminophylline-induced convulsions. The effect of the extract on phenobarbitone induced sleeping time was also evaluated. Results: The extract was found to significantly (p<0.001) decrease the frequency of line crossing, rearing and walling activities of the rats in open field test as well as increased the immobility time in both tail suspension and force swimming tests. The stem bark extract also significantly (p<0.001) shortened the onset time of sleep and prolonged the duration of sleep induced by phenobarbitone sodium. The stem bark extract and fractions (30 – 90 mg/kg), could not offered significant protection against PTZand aminophylline induced convulsion, but were found to delay significantly (p<0.05 – 0.001) the onset of tonic/clonic convulsion and also prolonged the time of death of the treated mice. Conclusion: The stem bark of M. africana has depressant, sedating and anticonvulsant properties.

Psychopharmacological studies of Mammea africana stem bark extract

Herbal medicine is an integral part of the health care system in most developed and developing countries of the world. Objective: The stem bark of Mammea africana used traditionally in the treatment of mental disorders was evaluated for depressive effect on the central nervous system (CNS). Materials and Method: The stem bark extract was investigated for depressive activity in the open field, force swimming and tail suspension tests as well as its anticonvulsant potential against pentylene tetrazol and aminophylline-induced convulsions. The effect of the extract on phenobarbitone induced sleeping time was also evaluated. Results: The extract was found to significantly (p<0.001) decrease the frequency of line crossing, rearing and walling activities of the rats in open field test as well as increased the immobility time in both tail suspension and force swimming tests. The stem bark extract also significantly (p<0.001) shortened the onset time of sleep and prolonged the duration of sleep induced by phenobarbitone sodium. The stem bark extract and fractions (30 – 90 mg/kg), could not offered significant protection against PTZand aminophylline induced convulsion, but were found to delay significantly (p<0.05 – 0.001) the onset of tonic/clonic convulsion and also prolonged the time of death of the treated mice. Conclusion: The stem bark of M. africana has depressant, sedating and anticonvulsant properties.

Synthesis, characterization and biological activity of diorgano and triorganotin (IV) complexes of Chlordiazepoxide, Choline theophyllinate and Phenobarbitone sodium

In an attempt to develop novel metal-based drugs with a different therapeutic profile to cisplatin, a new series of diorganotin (IV) and triorganotin (IV) complexes of R2SnA2 (R = Me, n-Bu, n-Oct and Phenyl) and R3SnA2 (R = n-Bu) where A is the anion of Chlordiazepoxide (L1H) {(2Z)-7-chloro-2-(methylimino)-5-phenyl-3,4-dihydro-2H-1,4-benzodiazepin-4-ol}, Choline theophyllinate (L2H) {(2-hydroxyethyl)trimethylazanium; 1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-ide} and Phenobarbitone sodium (L3H) {5-ethyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione} have been synthesized. These resulting complexes were characterized by elemental analysis, UV, IR, NMR (1H, 13C and 119Sn) studies. On the basis of these spectroscopic studies, it was proposed that diorganotin (IV) complexes of Chlordiazepoxide, Choline theophyllinate and Phenobarbitone sodium having 1:2 stoichiometry show tetrahedral geometry. Triorganotin (IV) complexes of Chlordiazepoxide and Choline theophyllinate having 1:2 stoichiometry show trigonal bipyramidal geometry. The ligand molecules in these complexes appear to be bound to the tin atom through the hydroxyl oxygen in Chlordiazepoxide, Choline theophyllinate and Phenobarbitone sodium. The biological activity of all these complexes was screened against six indicator strains: Bacteriodes fragilis, Salmonella enterica, Listeria monocytogenes, Pseudomonas aeruginosa, Escherichia coli and Vibrio cholerae. The antibacterial activity is found maximum for n-Bu2Sn(L2)2 which is most effective against all indicator strains used. n-Bu2Sn(L1)2 is effective against Pseudomonas aeruginosa and Vibrio cholerae while Me2Sn(L3)2 and Ph2Sn(L3)2 show good inhibitions against Bacteriodes fragilis and Salmonella enterica.

Evaluation of GABAergic Transmission Modulation as a Novel Functional Target for Management of Multiple Sclerosis: Exploring Inhibitory Effect of GABA on Glutamate-Mediated Excitotoxicity.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) where the communication ability of nerve cells in the brain and spinal cord with each other gets impaired. Some current findings suggest the role of glutamate excitotoxicity in the development and progression of MS. An excess release of glutamate leads to the activation of ionotropic and metabotropic receptors, thus resulting in accumulation of toxic cytoplasmic Ca2+ and cell death. However, it has been observed that gamma-aminobutyric acid-A (GABAA) receptors located in the nerve terminals activate presynaptic Ca2+/calmodulin-dependent signaling to inhibit depolarization-evoked Ca2+ influx and glutamate release from isolated nerve terminals, which suggest a potential implication of GABAA receptor in management of MS. With this proof of concept, we tried to explore the potential of selective GABAA receptor agonists or positive allosteric modulators (diazepam and phenobarbitone sodium) and GABAA level enhancer (sodium valproate) for management of MS by screening them for their activity in experimental autoimmune encephalomyelitis (EAE) model in rats and cuprizone-induced demyelination model in mice. In this study, sodium valproate was found to show the best activity in the animal models whereas phenobarbitone sodium showed moderate activity. However, diazepam was found to be ineffective.

Evaluation of antiepileptic activity of chloroform extract of Acalypha fruticosa in mice.

Aim:The aim of the present study is to evaluate the antiepileptic activity of chloroform extract of aerial parts of Acalypha fruticosa in mice.Materials and Methods:The antiepileptic activity of chloroform extract of A. fruticosa at the doses of 30, 100 and 300 mg/kg, p.o. was evaluated by maximum electroshock (MES), pentylenetetrazole (PTZ) and isoniazid (INH)-induced convulsions in mice. Statistical analysis was carried out by one-way analysis of variance followed by Dunnett's test.Results:In MES method, the chloroform extract significantly protected the mice from convulsions induced by electroshock method in a dose-dependent manner and exhibited more activity at the dose of 300 mg/kg when compared with diazepam treated animals. In PTZ method, the extract inhibited convulsions in mice potent than phenobarbitone sodium. In INH method, it delayed the latency of convulsions in mice in a dose-dependent manner but failed to protect the mice against mortality.Conclusion:The chloroform extract exhibited significant and dose-dependent antiepileptic activity, which may be due to the presence of antioxidant principles like flavanoids.

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.

The effect of naringin on early growth and development of the spheno-occipital synchondrosis as measured by the expression of PTHrP and Sox9--an in vitro model

The aim of this study was to assess the effect of the flavonoid naringin on the growth of the spheno-occipital synchondrosis by quantifying the levels of expression of Sox9 and PTHrP in an in vitro mouse model. Fifty 1-day-old BALB/c mice were randomly assigned to experimental or control groups, and each group equally divided into five time frames (6, 24, 48, 72 and 168 hours). The mice were sacrificed with phenobarbitone sodium, and the spheno-occipital synchondroses dissected and cultured in control or experimental medium, with the experimental medium supplemented with 0.1 µm naringin. Sections of the specimens underwent immunohistochemical staining for Sox9 and PTHrP, and the amount of expression was quantified using true-colour RGB (red-green-blue) computer-assisted image-analysing system with digital imaging. Data analysis showed there was a significant increase of expression of Sox9 at 6 and 24 hours (P < 0.001) between experimental and control groups, however, there was no significant difference between the levels of expression of PTHrP between experimental and control groups at any of the time frames. There was a very weak correlation found in this study between the expression of PTHrP and Sox9. In conclusion, naringin enhances the growth of the spheno-occipital synchondrosis through over expression of Sox9. This is a successful in vitro model to study factors regulating the growth of the spheno-occipital synchondrosis.