Drug Diazepam Research Articles

Nootropic Effects of C. melo and C. lanatus seed extracts.

Dementia and related conditions disturb the ability to perform routine life activities prohibiting a person from making appropriate decisions. Seeds of Cucumis melo and Citrullus lanatus have been investigated extensively for various pharmacological properties; hence, considering the presence of bioactive compounds, it was assumed that these seed extracts may support the functioning of the central nervous system. Thus, the present study was designed to investigate the short-term and long-term memory-enhancing effects of C. melo and C. lanatus seed extracts in mice by the Morris water maze (spatial learning and memory), stationary rod test, and passive avoidance tests (fear-motivated tests). Ethanol extract of both seeds were prepared by standard procedure and given to animals in the doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. The results were compared to standard drugs diazepam and imipramine given in the doses of 3 mg/kg and 30 mg/kg, respectively. Extracts of both the seeds were found to possess significant memory and cognition-enhancing effects in mice when tested by passive avoidance, stationary rod, and water maze tests. Results demonstrate memory and cognition-enhancing effects of these extracts which may be due to the presence of bioactive compounds in these seeds.

Impacts of chronic exposure to sublethal diazepam on behavioral traits of female and male zebrafish (Danio rerio)

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 μg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.

Identification of Anxiolytic Potential of Niranthin: In-vivo and Computational Investigations

Anxiety is an unpleasant state, which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination. Niranthin is a lignan isolated from various Phyllanthus sources. The literature survey on niranthin highlights wide ranges of the therapeutic potentials. In a present study, based on our previous investigations, we evaluated pure, isolated and characterized niranthin as an anxiolytic agent. The niranthin [6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole] was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test (EPM) and Light & Dark Exploration test (L&D). GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task. Molecular docking simulation studies (pdb id: 4COF) carried out by Vlife QSAR software showed that niranthin (docking score: − 62.1714 kcal/mol) have shown comparatively best docking score compared to the standard drug Diazepam (docking score: − 63.1568 kcal/mol). To conclude, Niranthin has probable potential in the management of anxiety disorder. Our in-silico and in-vivo analysis (indirectly) indicated the plausible role of GABA mediation for anxiolytic activity. Although, these studies are preliminary, future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future.Graphic

Evaluation of the anxiolytic effects of the aqueous and ethanolic extracts of the leaves and bark of Annona muricata using the elevated plus maze test

Introduction: Natural products since time immemorial have been the source of traditional medicine. A number of well-known anxiolytic agents currently used have several side effects that limit their use. Among medicinal plants, leaves of Annona muricata (AM) are being recommended by traditional healers for the management of anxiety. This study is performed to evaluate the anxiolytic activity of the aqueous and ethanolic extracts of the leaves and bark of Annona muricata. Methodology: Aqueous and ethanolic extracts of the leaves and bark of Annona muricata were prepared and assessed for anxiolytic effect using the elevated plus maze (EPM) model. The antianxiety activity of the extracts were compared to the control (distilled water 10ml/kg) and standard drug Diazepam (5mg/kg). Results and discussion: All doses of the aqueous leaf extract of Annona muricata exhibited significant increase in mean entries into open arms (P<0.01) and mean time spent in open arms (P<0.05) compared to the control. 100mg/kg and 400mg/kg of the ethanolic bark extract of Annona muricata showed significant increase in open arm entries (P<0.01) with 100mg/kg also showing an increase in time spent in open arms which was significant. Conclusion: This study demonstrated that both the aqueous and ethanolic extracts of the leaves and bark of Annona muricata exert an anxiolytic effect on rats which substantiates its traditional use in the management of anxiety.

Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish.

Epilepsy affects 50 million people around the world, and the patients experience cognitive, psychological and social consequences. Despite the considerable quantity of antiepileptic drugs available, 30% of patients still suffer in seizure. Therefore, the advance in therapeutic alternatives is mandatory. Resveratrol has been attracting the attention of many researchers because of its pharmacological potential. However, despite its neuroprotective and anti-epileptic effects, clinical resveratrol use is impaired by its low bioavailability. Here, we applied the supercritical fluid micronization technology (SEDS) to overcome this deficit, and investigated the anticonvulsant potential of micronized resveratrol in a PTZ-induced seizure model in adult zebrafish (Danio rerio). SEDS permits obtaining significantly reduced particle size with a fine size distribution in comparison with the starting material. It can improve the pharmacotherapeutic efficacy. Our data showed that micronized resveratrol decreased the occurrence of the tonic-clonic seizure stage and slowed the development of the seizures in a similar manner of diazepam. Non-processed resveratrol was not able to protect the animals. Furthermore, diazepam decreased the locomotion and exploratory behavior. Differently from diazepam, the micronized resveratrol did not induce behavioral adverse events. In addition, our data showed that the PTZ-induced seizures increased the c-fos transcript levels following the neural excitability. However, the increase in c-fos levels was prevented by micronized resveratrol. In conclusion, our results demonstrate that the micronized resveratrol shows anticonvulsant effect, like the classical antiepileptic drug diazepam in a PTZ-induced seizure model. Excitingly, different from diazepam, micronized resveratrol did not provoke behavioral adverse events.

Exploration of in vitro thrombolytic, anthelminthic, cytotoxic and in vivo anxiolytic potentials with phytochemical screening of flowers of Brassica nigra

BackgroundBrassica nigra is a plant of Brassicaceae family, which possesses numerous medicinal values. Our present study is intended to assess the potential in vitro thrombolytic, anthelminthic, cytotoxic and in vivo anxiolytic properties of MCE of B. nigra flowers. MCE was fractioned for separating the compound on the basis of polarity by using chloroform, n-hexane and ethyl acetate solvent. Thrombolytic and anthelminthic activities were explained by collecting human erythrocytes and earthworms as test models, respectively. Anxiolytic activity was evaluated by elevated plus maze and hole board models while cytotoxic test was conducted through brine shrimp lethality bioassay.ResultsMCE revealed the presence of alkaloids, flavonoids, tannin, diterpenes, glycosides, carbohydrates, phenols, fixed oils and fat. In case of thrombolytic test, the MCE, CSF, ASF and n-HSF had produced maximum clot lysis activity at 5 and 10 mg/ml dose conditions. Two different concentrations (10 and 20 mg/ml) of MCE and its fractions showed significant (p < 0.05) anthelminthic activities in a dose-dependent manner. Significant anxiolytic activity was observed for all fractions which was comparable to the standard drug diazepam (p < 0.05). Again, the cytotoxic screening also presented good potentials for all fractions.ConclusionFrom the findings of present study, we can conclude that MCE of B. nigra flowers and its fraction possess significant anxiolytic, anthelmintic, anticancer and thrombolytic properties which may be a good candidate for treating these diseases through the determination of bio-active lead compounds.

Shared structural mechanisms of general anaesthetics and benzodiazepines.

SummaryMost general anesthetics and classical benzodiazepines act through positive modulation of γ-aminobutyric acid type A (GABAA) receptors to dampen neuronal activity in the brain1–5. Direct structural information for how these drugs work at their physiological receptor sites is absent for general anesthetics. Here we present high-resolution structures of GABAA receptors bound to intravenous anesthetic, benzodiazepine, and inhibitory modulators. These structures were solved in a lipidic environment and complemented by electrophysiology and molecular dynamics simulations. Structures in complex with the anesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, shared in part by the benzodiazepine diazepam. Structures bound by antagonistic benzodiazepine-site ligands identify a novel membrane binding site for diazepam and suggest an allosteric mechanism for anesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinctive mechanisms to potentiate inhibitory signaling in the brain.

Synthesis and Evaluation of Anticonvulsant Activity of Some Schiff Bases of 7-Amino-1,3-dihydro-2H-1,4-benzodiazepin-2-one.

A variety of 1,3-dihydro-2H-1,4-benzodiazepin-2-one azomethines and 1,3-dihydro-2H-1,4-benzodiazepin-2-one benzamide were prepared, characterized and evaluated for the anticonvulsant activity in the rat using picrotoxin-induced seizure model. The prepared 1,3-dihydro-2H-1,4-benzodiazepin-2-one azomethine derivatives emerged potentially anticonvulsant molecular scaffolds exemplified by compounds, 7-{(E)-[(4-nitrophenyl)methylidene]amino}-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 7-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 7-{(E)-[(4-bromo-2,6-difluorophenyl)methylidene]amino}-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one and 7-[(E)-{[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]methylidene}amino]-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one. All these four compounds have shown substantial decrease in the wet dog shake numbers and grade of convulsions with respect to the standard drug diazepam. The most active compound, 7-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, exhibited 74 % protection against convulsion which was higher than the standard drug diazepam. Furthermore, to identify the binding mode of the interaction amongst the target analogs and binding site of the benzodiazepine receptor, molecular docking study and molecular dynamic simulation were carried out. Additionally, in silico pharmacokinetic and toxicity predictions of target compounds were carried out using AdmetSAR tool. Results of ADMET studies suggest that the pharmacokinetic parameters of all the target compounds were within the acceptable range to become a potential drug candidate as antiepileptic agents.

Transformation of diazepam in water during UV/chlorine and simulated sunlight/chlorine advanced oxidation processes

Psychoactive drug diazepam is one of benzodiazepines widely used in human medicine. It has been found to be relatively resistant to chlorination and photolysis. Here we investigated the transformation mechanism of diazepam in aqueous solution through UV/chlorine and simulated sunlight/chlorine treatments. The results showed that the UV/chlorine and sunlight/chlorine processes significantly increased the degradation of diazepam in water. These observed degradations can be elucidated by in-situ generation of reactive species including hydroxyl radical (HO), reactive chlorine species (RCS) and ozone (O3) during photolysis of chlorine. In the UV/chlorine treatment, the degradation efficiency of diazepam for HO, chlorine, UV and RCS reaction at 90 min was calculated to be 62.1%, 3.8%, 11.9% and 12.3%, respectively. In the simulated sunlight/chlorine treatment, the calculated degradation of 53.1%, 8.1% and 11.2% was attributed to HO, chlorine and RCS reaction, with negligible loss by O3 reaction and sunlight irradiation. In the UV/chlorine and sunlight/chlorine treatments, a total of 70 transformation products was detected using a high-resolution TripleTOF mass system. Six transformation pathways have been tentatively proposed for the diazepam, which includes hydroxylation, chlorination, hydrolyzation, N-demethylation, loss of phenyl group, benzodiazepine ring rearrangement and contraction. Most of the obtained transformation products were less toxic to aquatic organisms including fish, daphnia and green algae than diazepam itself according to the toxicity prediction tool, and did not cause significant changes in toxicity to luminescent bacteria.

O GEOGEBRA COMO POTENCIALIZADOR NA APLICAÇÄO DE FUNÇÃO EXPONENCIAL

Este trabalho apresenta uma experiência transcorrida a partir de uma proposta de atividade na disciplina Tópicos Especiais de Cálculo do Mestrado Profissional em Ciências da Universidade Estadual de Roraima - UERR, no segundo semestre de 2016 com o objetivo de analisar como o software GeoGebra contribui para a resolução de um problema que propunha determinar como ocorre o processo de eliminação do medicamento Diazepam no organismo do paciente usuário. Evidenciou-se que os recursos disponibilizados no software GeoGebra contribuem sim para a resolução de problemas que envolvem uma possibilidade de aplicação de Função Exponencial.

Short-term and persistent impacts of sublethal exposure to diazepam on behavioral traits and brain GABA levels in juvenile zebrafish (Danio rerio)

Environmental pollution by the psychoactive drug diazepam (DZP) has been suggested to disrupt various behavioral traits of fishes. Exposure to DZP in natural waters may be of episodic duration, but there are few reports on the persistence of abnormal behaviors of fishes caused by such acute exposure. In the current study, we exposed juvenile zebrafish (Danio rerio) to sublethal doses of DZP (1200, 120, and 12 μg/L) for four days and evaluated their behavioral traits and brain γ-aminobutyric acid (GABA) levels at days 0 (i.e., immediately after the 4-day exposure), 7, and 21 of the recovery period. Exposure to DZP induced short-term impairment of swimming ability and two-fish interactions of zebrafish. In contrast, DZP induced persistent and/or delayed effects on locomotor activity of zebrafish, i.e., hypoactivity at 1200 μg/L and hyperactivity at 120 and 12 μg/L, that could be still observed on days 7 and/or 21 during the recovery period. DZP exposure also exhibited concentration-specific effects on brain GABA levels in zebrafish, i.e., decreased at 1200 μg/L and increased at 120 and 12 μg/L. Correlation analysis suggested that the changes in brain GABA levels may contribute to the persistence of abnormalities in the locomotor activity of zebrafish. Our findings suggest that zebrafish need a long time to recover from acute exposure to DZP, thus highlighting that the persistence of behavioral abnormalities induced by such psychoactive drugs should be considered in order to better assess their risks in natural ecosystems.

Characterization of the Interaction of Daptomycin With Site II on Human Serum Albumin

Daptomycin, a cyclic lipopeptide antibiotic, is clinically used for the treatment of infections caused by Gram-positive bacteria, including the methicillin-resistant Staphylococcus aureus and the vancomycin-resistant Enterococci. While daptomycin shows high plasma protein binding (90–93%), our knowledge of the binding process is not extensive. To address this issue in more detail, we characterized the binding of daptomycin to plasma proteins and the findings indicate that the association constant for the binding of daptomycin to human serum albumin (HSA) is much higher than that for α1-acid glycoprotein, another plasma protein. Daptomycin was also found to bind to a single site on HSA, which was identified as site II. The findings also suggest that the n-decanoyl moiety of daptomycin penetrates into the hydrophobic pocket of site II and that this acyl moiety interacts with Tyr411 at the entrance to site II. Due to this selective interaction with site II, daptomycin binding was significantly inhibited by drugs (ibuprofen or diazepam) and endogenous compounds (uremic toxins or fatty acids) which also strongly bind to site II. In diseased states, such an inhibition in the binding could result in the pharmacokinetics and therapeutic action of daptomycin being substantially altered.

Design, synthesis and neuropharmacological evaluation of new 2,4-disubstituted-1,5-benzodiazepines as CNS active agents

Benzodiazepines (BZDs) represent a class of privilege scaffold in the modern era of medicinal chemistry as CNS active agents and BZD based drugs are used to treat different psychotic disorders. Inspired from the therapeutic potential of BZDs as promising CNS active agents, in the present work three different series of 1,5-benzodiazepines bearing various substitutions at position 2 and 4 of the benzodiazepine core were synthesized by condensing different substituted chalcones with o-phenylenediamine in the presence of piperidine as a base catalyst. Structural characterization of title compounds was done by using various analytical techniques such as IR, NMR, elemental analysis and mass spectral data. All the synthesized compounds (9a-d, 10a-e and 11a-c) were subjected to in vivo neuropharmacological studies to evaluate their CNS depressant and antiepileptic activity. Results of in vivo evaluation data showed that analogue 11b exhibited potent CNS depressant activity which was comparable to the standard drug diazepam. Compounds 10b and 10c displayed significant antiepileptic activity however they were less potent than the standard drug phenobarbitone. Molecular docking studies were performed using MOE software to find the interaction pattern and binding mode at the GABAA receptor (PDB Id: 6HUP). The results of the docking studies were in good agreement with the observed in vivo activity and revealed the satisfactory binding mode of the compounds within the binding site of the protein. The docking scores for the most promising candidates 10c, 11b and Diazepam were found to be −9.18, −9.46 and −9.88, respectively. Further, the compounds showed compliance with the Lipinski’s ‘rule of five’ and exhibited favourable drug-likeness scores. The identified leads can be explored further for the design and development of new BZD based psychotropic agents.

Synthesis and anxiolytic activity of 3-aryl-1-(41methoxyphenyl)-1-(6,7,8,9-tetrahydro5H -[1,2,4] triazolo[4,3-a]azepine-3-yl-methyl)- urea derivatives

Anxiety disorders are a widespread and growing problem of healthcare across the world. According to WHO data, neurosis and psychopaties are observed in 5–15 % of world population. In developed countries, about 20 % of population take anxiolytics permanently, and 30 % periodically. According to the WHO data it should be noted, that those pathologies affect different segments of population, from pediatric to geriatric population. Therapy of such nosologies imposes great loses on both individuals and society. 3-(41-Methoxyphenyl)-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-3-yl-methyl)-аmine was obtained by condensation of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine with (4-methoxyphenylamino) acetic acid hydrazide and further cyclization of the intermediate product. 3-Aryl-1-(41-methoxyphenyl)1-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-3-yl-methyl)-urea derivatives were obtained by condensation of 3-(41-methoxyphenyl)-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-3-ylmethyl)-аmi ne with appropriate arylisocyanates in dry benzene medium. The aim of the study – to synthesize and study an anxiolytic activity of 3-aryl-1-(41-methoxyphenyl)1-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-3-yl-methyl)-urea derivatives in comparison with known drugs diazepam and gidazepam on the stage of primary pharmacological screening. Tranquilizing activity of compounds was evaluated on models of «open field», «corazol convulsions» and «wire test» on mice, after administration at doses, equimolar to ED50 of diazepam. Diazepam (2 mg/kg) and gidazepam (2 mg/kg) were used as referent compounds. There were established, that 3-aryl-1-(41-methoxyphenyl)-1-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-3-yl-methyl)-urea derivatives are characterized by anticonvulsant and anxiolytic activity. The absence of muscle relaxant effect and absence or moderate inhibition of horizontal activity, suggest the absence of GABAergic component in specific activity of studied compounds. Anticonvulsant and behavioral activity («open field») of studied compounds depend on modification of substitutes on para- and ortho- positions of benzene ring of N`-group of urea. By specific activity, researched compounds are not inferior (or exceed) daytime tranquilizer gidazepam. On open field model compound 1-(41-methoxyphenyl)-1-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a] azepin-3-yl-methyl)-3-(p-tolyl)-urea 5 d is characterized by lesser influence on horizontal, vertical and exploration activity, while grooming and quantity of feces droppings are significantly inhibited. This indicates less sedation in comparison to such of diazepam. However, on open field model compound 5 d exceeds daytime tranquilizer gidazepam by results of primary screening.

Reliability of behavioral test with fish: How neurotransmitters may exert neuromodulatory effects and alter the biological responses to neuroactive agents

Toxic agents such as pharmaceuticals and pesticides are continuously dispersed especially in the aquatic environment, as a result of human use. Their presence in the environment presents serious concerns, since these compounds interfere with the normal function of the central nervous system (CNS), causing behavior alterations, whose consequences are difficult to predict. However, behavioral responses, even those that occur after exposure to neurotoxic agents, might be modulated by the release of neurotransmitters in the brain of exposed organisms, making even more difficult to ascertain the real consequences of pollution by neurotoxic or neuroactive agents. This study aimed to understand the potential of dopamine as neuromodulator in cases of acute exposure to a pesticide (the carbamate carbofuran) and to a therapeutic agent (the benzodiazepinic drug diazepam) in the freshwater fish Gambusia holbrooki. After acute exposure to both carbofuran and to diazepam it was possible to observe deleterious alterations in the motor function, reflected by significant reductions of both average speed and distance in exposed animals. These changes were later diminished and reverted by dopamine exposure. Despite the indications obtained from our experiments, more research is needed to clarify the consequences of these behavior alterations in a more integrative perspective, namely by adding behavioral endpoints of increased ecological relevance to the adopted experimental design.

POTENTIALLY INAPPROPRIATE MEDICATION USE IN GERIATRIC BASED ON 2015 BEERS CRITERIA

The purpose of this research is to analyze the use of drug prescribing in outpatient geriatric patients in hospital Jambi City period August 2016 to August 2017. The study was conducted in December 2017 through March 2018 using an explicit criteria screening tool of Beers 2015. This research is observational research with a descriptive design of retrofit data on the prescription of outpatient geriatric patients in one of Jambi city hospitals. Based on Polyclinic origin, most patients come from the disease (22 %). Use of the drug in the treatment of outpatient geriatric patients in one of the Jambi city hospitals as much as 239 prescriptions (79.4 %) The criteria included in Beers 2015. There are eight recipes containing more than one type of medication (3.4 %). The use of drugs in the prescription of geriatric patients included in Beers 2015 criteria is high enough with the prevalence of the use of the most widely used drugs diazepam and mefenamic acid. Drug used in geriatric patients at X hospital who were included in the 2015 Beers Criteria are alprazolam, amitriptyline, mefenamic acid, clonazepam, diazepam, digoxin, ibuprofen, ketoprofen, ketorolac, meloxicam, sodium diclofenac, Ranitidine, Spironolactone and Trihexefenidil. Keywords : Geriatric, Beers Criteria 2015, Retrospective

Kainic acid-induced seizures in the common marmoset

Treatment of epilepsy remains difficult because patients suffer from pharmacoresistant forms of the disease and drug side-effects. Thus, there is an urgent need to identify not only new antiepileptic drug candidates but also novel epileptic animal models. Here, we characterize seizures induced with kainic acid (KA) in the common marmoset (Callithrix jacchus). Adult marmosets received 0.1, 1, or 10 mg/kg of KA subcutaneously. All animals exhibited early convulsive behavior (seizure scores of I and II on the Racine scale). Seizure scores were low at lower KA doses, but the highest dose of KA tested triggered generalized seizures (scores IV and V on the Racine scale). We next performed preliminary evaluation of the efficacy of the antiepileptic drug diazepam. This drug at 1 mg/kg (delivered subcutaneously) prevented 10 mg/kg KA-induced stage V seizures. KA administration to marmosets reliably triggers generalized seizures; therefore, the marmoset is a useful animal model in which to analyze the seizures of a nonhuman primate brain and to develop new treatments for epilepsy.

Diazepam and electrical stimulation of paleocerebellar cortex inhibits seizures in pentylenetetrazol-kindled rats

The cerebellum is a potent anti‑epileptic target for deep brain stimulation in patients with drug‑resistant epilepsy. The effects of such stimulation, however, may also favor seizure activity. Our goal was to investigate the effect of cerebellar electrical stimulation (ES) alone and in combination with the anti‑epileptic drug diazepam (DIA) on seizure outcome. We used a rat model of pentylenetetrazol kindling, which is characterized by seizures followed by deteriorations in central benzodiazepine‑GABAA (BDZ‑GABAA) receptors. We tested the effects of ES alone and in combination with DIA (0.1 and 1.0 mg/kg) on seizures. Our data demonstrated: 20 ES trials can prevent the recurrence of clonic‑tonic kindled seizures, administration of either DIA‑0.1 or ES (5 trials) alone is ineffective on seizures, and combining DIA‑0.1 and 5 ES or DIA‑1.0 and 5 ES caused an additive effect, prolonged the latency to seizure onset, and prevented recurrence of clonic‑tonic seizures. We also observed that ES alone produced either facilitation or inhibition of seizures on EEG. In contrast, the same ES inhibited EEG seizures when delivered after a combination of DIA‑1.0 and 5 ES and ultimately prevented the facilitation of the discharges. Lastly, we demonstrated that seizure suppression is intensified when cortical ES is performed after DIA administration. Our data supported the hypothesis that both BDZ‑GABAA receptor activity along with cerebellar output comprise the potential mechanisms underlying the peculiar effects of deep brain stimulation in the cerebellum on seizures.

EVALUATION OF DIURETIC AND SEDATIVE ACTIVITY FOR ETHANOLIC LEAVES EXTRACT OF BASELLA ALBA L. VAR RUBRA

Herbal medicine is the oldest form of health care known to mankind. Medicinal plants can be important sources of unknown chemical substances with potential therapeutic effects. The study of plant species with diuretic effects is still a fruitful research in search of new diuretic and sedative drugs. The present study was carried out to evaluate the diuretic and sedative effect of ethanolic extract of Basella alba (BAE) in wistar rats & mice by using Lipschitz model and Rota rod model respectively. The urine volume, electrolyte levels in rats and fall of time of mices from rota rod were measured. BAE showed significant (p<0.05) diuretic and sedative activity of two doses (100mg/kg & 200mg/kg, p.o) tested, When compared to control and drugs furosemide and diazepam respectively. Hence, the BAE possess diuretic and sedative activity.

A Comprehensive Study of the Neuropharmacological Profile of Methanol Leaf Extract of Aloe vera and Identification of Associated Neuroprotective Compounds through Gas chromatography-mass spectrometry Analysis

The objective of this study is to determine the neuropharmacological activities of the methanol extract of Aloe vera leaf and identify the potential bioactive compounds present in the same responsible for the activities through Gas chromatography–mass spectrometry analysis. The study is done on Wistar albino rats and composed of 5 groups, methanol extract of Aloe vera leaf at 200, 400, 800 mg/kg, normal saline (control) and standard drugs Phenytoin and Diazepam. Antiepileptic activities are done using maximal electroshock and pentylenetetrazole induced convulsion models and anxiolytic sedative activities using the staircase test, actophotometer test and sleep prolongation test. The chemometric analysis is performed using Clarus 500 Perkin Gas Chromatograph coupled with a mass detector, Turbo mass gold–Perkin Elmer Turbomass 5.1 spectrometer with an Elite-1 (100 % dimethyl polysiloxane), 30 m×0.25 mm ID×0.25 μm of the capillary column. The results demonstrated anxiolytic potential at 200 and 400 mg/kg and sedative activity at 800 mg/kg comparable to Diazepam. The methanolic extract of Aloe vera leaf at 800 mg/kg displayed antiepileptic activity compared to Phenytoin. The Gas chromatography–mass spectrometry analysis confirmed the presence of phytol (23.76), alpha-tocopherol (4.67), maltol (3.69), humulene (6.58), caryophyllene (2.73), n-hexadecanoic acid (2.16), hexadecanoic acid methyl ester (3.70), squalene (3.51), 9,12,15-octadecatrienoic acid methyl ester (2.12), which are antioxidant and anti-inflammatory compounds. These plant derived bioactive compounds are demonstrated to have antianxiety, antiepileptic, sedative hypnotic and neuroprotective potential in neurodegenerative models and might serve as future prospective drug candidates in neurodegenerative disorders).