Drug Diazepam Research Articles

Evaluation of Antianxiety Effect of Mucuna Pruriens (L) –An Experimental Study in Wistar Albino Rats.

Mucuna Pruriens (MP) is a plant legume growing well in tropical countries like Africa and Asia. Various parts of this plant are used in traditional medicine to treat diseases like Parkinsonism and male infertility and as anabolic agents. These effects are attributed to the biologically active components with antioxidant properties. Many studies are highlighting the antiparkinsonian effect of MP. Twenty-four Wistar albino rats were used in this study to investigate the antianxiety activity. The animals were separated into four groups of six (Control, Diazepam-5mg/kg, MP-200mg/kg, and MP-400/kg). All animals were tested for 18 weeks, with a six-week interval beginning with week one. This study aims to observe the effect of MP on anxiety on the Elevated Plus Maze (EPM). Effects of test drug and control were noted by observing the time spent in the Open & Closed arm of EPM and the number of entries into the open & closed arm and compared among the four groups. Observations were analyzed using One-way ANOVA & Dennett's multiple comparisons tests. Animals treated with Mucuna Pruriens (200, 400mg/kg) produced a significantly increased number of entries and time spent in the open arm in the EPM (p<0.0001) compared with the control group. Mucuna Pruriens, used in this study at doses of 200mg/kg & 400mg/kg, shows an antianxiety effect comparable to that of the standard reference drug diazepam. Diazepam appeared to have a soothing effect, and no sedation was observed with MP powder based on the above results in this study.

Acacia catechu Willd. and Acacia arabica Willd. decrease the extent of anxiety behavior by reducing oxidative stress and moderating neurochemicals

Ethnopharmacological relevanceAnxiety is a very common psychiatric problem. It affects a large group of people in the world population. Acacia genus is well known for phenolic and flavonoid content. Literature showed its potential for various biological activities and is useful in the treatment of chest pain, asthma, bronchitis, wounds, mouth ulcer, colic, vitiligo, sore throat, inflammation, diarrhoea and also used as tonic. Aim of the studyThe present study was conducted to assess the antianxiety potential of two plants Acacia catechu Willd. and Acacia arabica Willd. from the common family Fabaceae. Materials and methodsThe stems of both plants were used for this purpose. Plants were subjected to complete exhaustive successive extraction using petroleum ether, chloroform, ethanol, and water as solvent. After pharmacognostic and phytochemical investigation, antianxiety activity was conducted on Swiss albino mice at different dose levels (100, 200, 300, & 400 mg/kg body weight p.o.) for all successive extracts of both plants. Two active extracts from each plant were further assessed for anxiolytic potential using the open-field test and mirror chamber test. One extract with the maximum response from each plant was further screened using mCPP-induced anxiety test. ResultsThe stem of ethanol extract of A. catechu showed comparable antianxiety activity at 400 mg/kg to the standard drug diazepam (2.5 mg/kg). Improved SOD, catalase, and LPO levels were noted after administration of A. catechu ethanolic extract at 400 mg/kg. ConclusionsIn conclusion, A. catechu ethanolic extract improved anxiety symptoms at dose-dependent levels in mice.

Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John’s wort

Phytomedicines such as valerian and St. John’s wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John’s wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts.

Dichotomine B Attenuates Neuroinflammatory Responses by Regulating TLR4/MyD88-mTOR Signaling Pathway in BV2 Cells.

Dichotomine B is a [Formula: see text]-Carboline alkaloid isolated from Stellariae Radix. Stellariae Radix, also known as Yin Chai Hu, is a common Chinese medicine in clinical practice. This herb has been demonstrated to have anti-inflammatory activity. This study aimed to investigate the effects and mechanisms of Dichotomine B on neuroinflammation by BV2 microglia induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The experiment was divided into a control group, a model group (10 µg/mL LPS + 5 mM ATP), a model+ TLR4 inhibitor (TAK-242, 10 µmol/L) group, model+ Dichotomine B (20, 40 and 80 µmol/L) groups and Dichotomine B (80 µmol/L) group. The BV2 cell viability was detected by MTT assay, the morphology of BV2 cells was observed by inverted microscope, and the levels of IL-6, IL-1[Formula: see text] and TNF-[Formula: see text] in BV2 cells were determined by ELISA. The expression levels of TLR4, MyD88, p-mTOR/mTOR, p62, p-RPS6/RPS6, LC3II/LC3I and Beclin-1 proteins were detected by western blot assay. The expression levels of TLR4, MyD88, mTOR, p62, RPS6, LC3B and Beclin-1 mRNA were detected by PCR assay. Finally, molecular docking was performed to predict the affinity of Dichotomine B with TLR4, MyD88 and mTOR by LibDock of Discovery Studio and MOE. The results showed that compared with the model group, the survival rates of damaged cells were significantly increased by TAK-242 and Dichotomine B, and the morphology of these BV2 cells improved. The levels of IL-6, IL-1[Formula: see text] and TNF-[Formula: see text] were significantly decreased by TAK-242 and Dichotomine B in LPS/ATP-induced BV2 cells. 80 µmol/L Dichotomine B has no effect on normal BV2 cells. Further mechanism investigation showed that TAK-242 and Dichotomine B significantly inhibited the protein and mRNA expression levels of TLR4, MyD88, p-mTOR/mTOR (mTOR), p62, p-RPS6/RPS6 (RPS6) and increased the protein and mRNA expression levels of LC3II/LC3I (LC3B), Beclin-1. Docking study showed the LibDock scores of Dichotomine B with TLR4, MyD88 and mTOR were all higher than those of positive drugs (Diazepam). These findings indicated that Dichotomine B attenuated neuroinflammatory responses in LPS/ATP-induced BV2 microglia, and its mechanism may be related to TLR4/MyD88-mTOR signaling pathway and autophagy.

Synthesis, Computational and Pharmacological Evaluation of 7-(2-(2- (3- (Substituted Phenyl) Acryloyl) Phenoxy) Ethoxy)-4-Methyl-2H-Chromen- 2-Ones as CNS Agents.

Motivated by the exciting biological potential for the use of hybrid molecules in medicine and therapy. It is anticipated that the coumarin-chalcone hybrids for skeletal muscle and antianxiety action will be investigated using a chemical hybridization technique. Due to its numerous benefits, including high effectiveness, mode of action at receptors, minimal adverse effects, and improved pharmacokinetic features, naturally occurring and synthesized hybrid compounds are prospective sources for novel drug development techniques. In opinion of these applications, we here designed some coumarin-chalcone hybrids and explored them for skeletal muscle and antianxiety potential. Using a chemical hybridization strategy, coumarin-chalcone hybrids have been synthesized and evaluated for skeletal muscle and antianxiety activity. The target compounds were synthesized by reaction of 7-hydroxy-4-methylcoumarion with haloalkane to afford 7-(2- bromoethoxy)-4-methyl-2H-chromen-2-one which was further treated with hydroxychalcones. The structures of target compounds were confirmed on the basis of their Melting Point, Thin Layer Chromatography, IR, 1HNMR and Mass studies. The computational properties of target compounds were also determined through online software. Skeletal muscle and antianxiety potential were performed in Swiss albino mice. The coumarin-chalcones hybrids showed skeletal muscle and antianxiety potential in Swiss albino mice and computational properties of the target compounds were also showed similarity as compared with diazepam. Among the target compounds, the fluoro group containing compound was found to be more potent as compared to the standard drug diazepam.

Antidepressant Activities of Synthesized Benzodiazepine Analogues in Mice

Depression is a serious psychological disorder which negatively affects human feelings and actions. The use of antidepressants is the therapy of choice while treating depression. However, such drugs are associated with severe side effects. There is a need for efficient and harmless drugs. In this connection, the present study was designed to synthesize several substituted benzodiazepine derivatives and explore their antidepressant potentials in an animal model. The chalcone backbone was initially synthesized, which was then converted into several substituted benzodiazepine derivatives designated as 1-6. The synthesized compounds were identified using spectroscopic techniques. The experimental animals (mice) after acclimatation were subjected to forced swim test (FST) and tail suspension test (TST) after oral administration of the synthesized compounds to evaluate their antidepressant potentials. At the completion of the mentioned test, the animals were sacrificed to determine GABA level in their brain hippocampus. The chloro-substituent compound (2) significantly reduced the immobility time (80.81 ± 1.14 s; p < 0.001 at 1.25 mg/kg body weight and 75.68 ± 3.73 s with p < 0.001 at 2.5 mg/kg body weight dose), whereas nitro-substituent compound (5) reduced the immobility time to 118.95 ± 1.31 and 106.69 ± 3.62 s (p < 0.001), respectively, at the tested doses (FST). For control groups, the recorded immobility time recorded was 177.24 ± 1.82 s. The standard drug diazepam significantly reduced immobility time to 70.13 ± 4.12 s while imipramine reduced it to 65.45 ± 2.81 s (p < 0.001). Similarly, in the TST, the compound 2 reduced immobility time to 74.93 ± 1.14 s (p < 0.001) and 70.38 ± 1.43 s (p < 0.001), while compound 5 reduced it to 88.23 ± 1.89 s (p < 0.001) and 91.31 ± 1.73 s (p < 0.001) at the tested doses, respectively, as compared to the control group immobility time (166.13 ± 2.18 s). The compounds 1, 3, 4, and 6 showed weak antidepressant responses as compared to compounds 2 and 5. The compounds 2 and 5 also significantly enhanced the GABA level in the brain's hippocampus of experimental animals, indicating the possible involvement of GABAergic mechanism in alleviating the depression which is evident from the significant increase in mRNA levels for the α subunit of the GABAA receptors in the prefrontal cortex of mice as well. From the results, it can be concluded that compound 2 and 5 could be used as alternative drugs of depression. However, further exploration in this connection is needed in other animal models in order to confirm the observed results in this study.

Electrical impedance spectroscopy for drug screening on ligand-gated ion channels.

Ligand-gated ion channels (LGICs) are involved in many pathophysiological processes and represent a relevant, although challenging, target for drug discovery. The gold standards for studying the ligand-induced ion channel currents and their modulations by drugs are manual patch clamp or two-electrode voltage clamp (TEVC) electrophysiology, but the throughput is low. Higher throughput has been achieved with automated patch clamp instruments, but these have immense acquisition and significant operating costs. In a proof-of-concept study, we developed a reliable, easy to use and multiplexable microfluidic setup to screen the action of drugs at LGICs heterologously expressed in X. laevis oocytes by measuring the electrical impedance changes across the plasma membrane induced by ligand pulses. We validated our setup by simultaneous TEVC electrophysiology and tested the effects of the reference drugs suramin, TNP-ATP, PPADS or diazepam on oocytes expressing P2X2 or GABAAreceptors, respectively. The drugs modulate ATP-induced and GABA-induced currents of P2X2 and GABAA receptors, respectively. The results obtained with TEVC are similar in terms of drug efficacy to those obtained with simultaneously recorded membrane impedances, which are determined by electrical impedance changes. Thus, the study shows the reliability of our setup as a faster (higher throughput) and more cost-effective method for drug screening compared to conventional electrophysiological techniques. After multiplexing of the system, the setup may facilitate commercial and academic drug screening of ligand gated ion channels that are receiving less attention due to limitations in current assays. [Funded under the Excellence Strategy of the Federal Government and the Länder - OPSF671]

Behavioral Despair Is Blocked by the Flavonoid Chrysin (5,7-Dihydroxyflavone) in a Rat Model of Surgical Menopause.

Women have a high susceptibility to the negative effects of stress. Hormonal changes experienced throughout their reproductive life partially contribute to a higher incidence of anxiety and depression symptoms, particularly, during natural or surgical menopause. In preclinical research, the flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic- and anti-despair-like effects; however, it is unknown whether chrysin exerts a protective effect against the behavioral changes produced by acute stress on locomotor activity and behavioral despair in rats at 12-weeks post-ovariectomy. Ovariectomized female Wistar rats were assigned to eight groups: vehicle group (10% DMSO), three groups with chrysin and three groups with the same dose of allopregnanolone (0.5, 1, and 2 mg/kg), and one group with diazepam (2 mg/kg). The treatments were administered for seven consecutive days and the effects were evaluated in the locomotor activity and swimming tests. Chrysin (2 mg/kg) increased the latency to first immobility and decreased the total immobility time in the swimming test as the reference drugs allopregnanolone and diazepam (2 mg/kg); while locomotor activity prevented the behavioral changes produced by swimming. In conclusion, chrysin exerts a protective effect against the behavioral changes induced by acute stress, similarly to the neurosteroid allopregnanolone and the benzodiazepine diazepam in rats subjected to a surgical menopause model.

Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats.

Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold.

Attenuation of Experimentally Induced Anxiety by Panchagavya Ghrita in Mice

The present study was undertaken to evaluate the effect of Panchagavya ghrita on experimentally induced anxiety in swiss albino mice. The study was carried out with an objective of scientifically validating the traditional claims and to compare the ancient knowledge with the latest pharmacological aspects of preclinical research. The Swiss albino mice were divided into 4 groups of 6 mice each. First group received vehicle 10mg/kg orally. Second group was treated with the standard drug diazepam (2mg/kg i.p) one hour before the experiment. Third and fourth group animals were treated with the two different doses of Panchagavya ghrita i.e., 4680mg/kg p.o and 6840mg/kg p.o once daily for 14 days. On the 15th day one hour after administration of the test dose, anti anxiety activity was evaluated using Elevated Plus maze model, Light Dark Transition model &amp; Open field test. Animals treated with Panchagavya Ghrita showed significant result by increasing the number of entries into the open arm and time spent in open arm in Elevated Plus maze model. In Light &amp; Dark Transition model, it showed increase in the Number of entries into the light chamber and time spent in the light chamber and in the open field test, the number of rearings, time spent in the central square and the number of squares crossed increased thus proving the antianxiety activity of Panchagavya ghrita.

Design, Synthesis and Pharmacological Evaluation of Novel C2,C3-Quinoxaline Derivatives as Promising Anxiolytic Agents.

A new series of quinoxaline derivatives, 2a-4b, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in 2a, 2b, 2c, 4b. Their anxiolytic properties were confirmed in terms of LDB and the most active was compound 2b. In the OF, only 2c had an influence on the locomotor activity of the rodents. Thus, the most promising substance was determined; this was 2b, which has the structure of 2-(2-{[3-(4-tert-butylphenyl)quinoxaline-2-yl]methyl}-4,5-dimethoxyphenyl)-N-methylethan-1-amine hydrochloride. The obtained data were analyzed with the pharmacophore feature prediction approach, which made it possible to compare the structures of the studied compounds with the reference drug diazepam, and to determine the contribution of pharmacophores to the manifestation of the activity under study. ADMET analysis was carried out for compound 2b and the acute oral toxicity of this substance was also tested in vivo. As a result of the study, a promising compound with a high anxiolytic effect and low level of toxicity 2b was found, which is of interest for further preclinical study of its properties.

Alprazolam Detection Using an Electrochemical Nanobiosensor Based on AuNUs/Fe-Ni@rGO Nanocomposite.

Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L-1 and 1 to 50 mg L-1), low limit of detection (1 µg L-1), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.

Anticonvulsant appraisal of benzylideneacetophenone analogues in Swiss mice

Background: Diketones and α,β-unsaturated ketone are useful intermediates for the synthesis of antiepileptic moieties. Epilepsy is a neurological disorder that affects about fififty million people worldwide. The aim of the study was to assess benzylideneacetophenone analogues for their potential antiepileptic effects in mice. Methods: The compounds used in the pharmacological assay which include; 4-Dimethylaminochalcone (A), 1(4-Nitrophenyl) – 3 (ϒ -benzopyranoyl)-2-propen – 1-one (B), 1(4' –Nitrophenyl) – 3 (1,3-benzodioxolyl) 2 – propen – 1 – one (C), 1-Phenyl-3- (benzodioxolyl) – 2 –propen – 1-one (D), 4-Chlorochalcone (E), 4'-Nitro-4-dimethylaminochalcone (F) 4'-Nitro-4-methoxychalcone (G), were assayed using three models; Strychnine, Pentylenetetrazole (PTZ) and Maximal Electroshock (MES). The samples were given at 500, 1000 and 1500 mg/kg while standard&nbsp;drug diazepam and distilled water were given at 5 mg and 10 ml/kg intraperitoneal respectively.&nbsp;Convulsion inducing agents (Strychnine 2 mg/kg and PTZ, 100 mg/kg) were administered intraperitoneal 1hour after the administration of test samples while MES model electroconvulsive&nbsp;shock was applied using electroconvulsive machine.&nbsp; Results: The samples (A-G) showed significant (P&lt;0.03, 0.003, 0.0007 and 0.0001) effect in delaying onset of seizure compared to control in strychnine model, while in PTZ model samples (A-F) evaluated at 500,1000 and 1500 mg/kg are equipotent at all the doses by signifificantly (P&lt;0.0001) and sample G (P&lt;0.0007) reduced the onset of seizure compared to control. However in MES model samples (A-F and G) evaluated at 500, 1000 and 1500 mg/kg are equipotent at all the doses by significantly (P&lt;0.0001; 0.0007), reduced the duration of seizure compared to control respectively.&nbsp; Conclusion: Benzylideneacetophenone analogues showed various effects in control of seizure in all the models used.This effect is due to delayed onset and reduction of seizure duration. The samples could act by stimulating the glycine, Gamma Aminobutyric acid (GABA) receptor, inhibition of&nbsp;GABAAminotransferase and prolong inactivation of sodium ion channel.

Evaluation of Antidepressant and Anxiolytic Activity of Fruit Extract of Hylocereus undatus in Experimental Animals

Hylocereus undatus, generally known as dragon fruit was used in the present study to investigate antidepressant and anti-anxiety activity. In antidepressant activity we found that administration of 200 mg/kg and 400 mg/kg ethanolic fruit extract of Hylocereus undatus (EFEHU) and standard drug imipramine (20 mg/kg) for 21 days to respective group of animals they showed significantly reduced the immobility time in both Tail suspension test (TST) and Despair swim test (DST) in dose dependent manner as well as biochemical estimation was done. In anxiolytic activity administration of 200 mg/kg and 400 mg/kg EFEHU and standard drug diazepam (2 mg/kg) for 14 days to respective group of animals. In Elevated plus maze test (EPMT) significantly increased time spent in open arm and number of entries in open arm. The significantly increased level of 5-HT and GABA in brain of mice in dose dependent manner in both DST and EPMT. The phytochemical study of EFEHU showed the presence of alkaloids, tannins, carbohydrates, flavonoids, terpenoids, saponins, oils, phenolic compounds and qualitative examination by HPTLC technique showed that presence of quercetin and gallic acid. Therefore, the presence of such compounds in the extract may be responsible for the antidepressant and anxiolytic activity. Therefore, present study validates its antidepressant and anxiolytic activity. Further, research is required to elucidate its specific mechanism of action and isolation of responsible active principles.

Behavioural studies on crude Ethanol leaf extract of Cadaba farinosa Forssk. in mice

Cadaba farinosa Forssk. (Capparaceae) is found all over the world, mostly in tropical and subtropical areas. It is used to treat pain, dysentery, rheumatism, cough, and fever, as well as an antidote and in the treatment of neurological disorders. In mice, the median lethal dose (LD50) of Crude Ethanol leaf Extract (CEE) of Cadaba farinosa was found to be 2154.1 mg/kg body weight. The presence of alkaloids, anthraquinones, carbohydrates, cardiac glycosides, flavonoids, glycosides, saponins, and tannins was discovered during a preliminary phytochemical analysis of the dark gummy mass crude extract. The CEE was then put through pharmacological testing on mice. In mice, diazepam-induced sleep, beam walking, and hole-board assays were used to investigate behavioral activities. CEE of Cadaba farinosa had no effect on the onset of sleep in mice when given at the tested doses of diazepam. In contrast, it significantly increased sleep duration at all doses tested (75 mg/kg p 0.001, 150 mg/kg p≤0.05, and 300 mg/kg p≤0.01). The CEE significantly (p≤0.01) increased the number of foot slips in the Beam walking assay at a dose of 150 mg/kg. Similarly, diazepam at 0.25 mg/kg increased the number of foot slips significantly (p≤0.001). The extract at a dose of 300 mg/kg and diazepam increased the time required to complete the task significantly (p≤0.05). At 150 mg/kg (p 0.01) and 300 mg/kg (p≤0.05), the hole-board experiment significantly reduced the number of head dips. In contrast, the standard drug (diazepam) had no discernible effect on the number of head dips. These findings suggest that CEE and Diazepam at the highest dose significantly affected the behaviour of mice in the beam walking assay. Thus, the extract showed no activity on the onset of sleep but significantly prolong duration of sleep at the tested doses. The CEE significantly produced a decrease in the exploratory behavioural pattern, indicative of the fact that CEE possesses sedative property.

Development of a Microgram Scale Video-Microscopic Method to Investigate Dissolution Behavior of Poorly Water-Soluble Drugs.

Poor aqueous solubility is a common characteristic of new drug candidates, which leads to low or inconsistent oral bioavailability. This has sparked an interest in material efficient testing of solubility and dissolution rate. The aim was to develop a microgram scale video-microscopic method to screen the dissolution rates of poorly water-soluble drugs. This method was applied to six drugs (carvedilol, diazepam, dipyridamole, felodipine, fenofibrate, and indomethacin) in fasted state simulated intestinal fluid (FaSSIF), of indomethacin in buffer with varying pH, and of diazepam and dipyridamole in customized media. An additional aim was to track phase transformations for carbamazepine in FaSSIF. The dissolution rates and particle behavior of the drugs were investigated by tracking particle surface area over time using optical video-microscopy. Applying miniaturized UV spectroscopic dissolution resulted in a similar grouping of dissolution rates and pH effects, as for the video-microscopic setup. Using customized media showed that lysophospholipid enhanced the dissolution rate of diazepam and dipyridamole. The video-microscopic setup allowed for the nucleation of transparent particles on dissolving carbamazepine particles to be tracked over time. The developed setup offers a material efficient screening approach to group drugs according to dissolution rate, where the use of optical microscopy helps to achieve a high sample throughput.

Study on effect of ethanolic extract of triticum aestivum in anxiety behaviour induced by chronic unpredictable stress in a rat model

Objectives- This study was undertaken to evaluate the effect of Ethanolic extract of Triticum aestivum (TAE) on different anxiety like behaviour induced by Chronic unpredictable stress in wistar albino rats. Materials and methods- Effect of TAE was studied on chronic unpredictable stress induced rats. The reference standard drug (Diazepam 1mg/kg po) and the test drug, TAE at doses of 150mg/kg and 200mg/kg b.w. were given to rats for 14 days. Anti-anxiety activity was assessed by using Light and Dark Box test. Then the locomotor activity of rats was assessed as indicator of anxiety. Animals were sacrificed at the end of this experiment..The adrenal and spleen weight, ulcer index as well as various biochemical parameters like Malondialdehyde (MDA) and Superoxide dismutase (SOD) were assessed. Results- The stay in Light box was increased, rearing activity was increased to a significant level in both Diazepam and TAE-200 mg/kg treated rats and this effect was comparable to that of normal non-stressed vehicle treated rats. Chronic stress caused elevation of MDA and depression of SOD level which is reversed by Ethanolic extract of Triticum aestivum (TAE).

Evaluation of extraction parameters in authentic hair reference material using statistical design of experiments.

Optimal methods for forensic hair analysis are often debated, especially regarding extraction parameters that include incubation time, temperature, and size of extracted hair particles. To assess hair pretreatment parameters for analysis of drugs of abuse, the statistical technique known as Design of Experiments (DoE) is useful. DoE evaluates both the individual roles and the combinatorial associations between multiple variables and overall drug extraction efficiency. Previous reports have focused on incorporated hair reference material (HRM), which is prepared in the lab at a specified drug concentration. In contrast, authentic HRM, which is prepared by diluting hair from drug users with blank hair to achieve specific drug concentrations, is an effective matrix for standardization of forensic hair testing, since the drug is incorporated into the hair matrix via uptake from systemic distribution. In the present study, extraction parameters for authentic HRM samples containing multiple drugs (diazepam, alprazolam, cocaine, methamphetamine, oxycodone, hydrocodone, and morphine) and metabolites (nordiazepam, cocaethylene, norcocaine, hydroxycocaine, and 6-monoacetylmorphine) were optimized based on recovery using a 23 full factorial DoE matrix. The factors evaluated included extraction solvent volume/sample weight ratio (12.5 or 25 μL/mg), particle size (pulverized or cut into 1 mm snippets), and extraction time (2 or 24 h) using solvent swelling. DoE analysis revealed significant differences in the optimal combinations of extraction parameters for maximum recovery. However, for the majority of drugs and metabolites, the most effective extraction method consisted of pulverizing hair prior to a 2-h extraction with a 12.5μL/mg extraction solvent volume/sample weight ratio.

Sleep Disruption Exacerbates Cognitive Dysfunction by Promoting Lipid‐Immune Dysregulation in the Corticohippocampal System of Pentylenetetrazol‐Kindled Rats

Sleep deprivation has been identified as one of the triggers for seizures in patients with generalised epilepsy. Therefore, we tested whether rapid eye movement (REM) sleep deprivation would increase susceptibility to developing generalised seizures established by pentylenetetrazol (PTZ) kindling; and whether REM sleep deprivation would affect treatment response and cognitive outcomes in epileptic rats. Furthermore, possible mechanistic underpinnings such as lipid‐immune responses in the prefrontal cortex and hippocampus were evaluated. Male rats were either sleep‐deprived followed by PTZ kindling, or kindled before being sleep‐deprived, or kindled before sleep deprivation and treated with a known anticonvulsant, diazepam. Thereafter, cognitive behaviours were evaluated. Following euthanasia, the prefrontal cortex and hippocampus were extracted and processed for biochemical and histological/histochemical/immunohistochemical assessments. Our results showed increased susceptibility to epileptogenesis in the group exposed to sleep deprivation before kindling compared to the PTZ‐kindling group without sleep deprivation. Also, sleep deprivation aggravated epilepsy features in the sleep‐deprived PTZ‐kindled rats and negatively impacted drug (diazepam) response in these animals. These were all linked to a disruption in lipid profile, and interleukin‐17 (IL‐17) activity; exacerbation in demyelination, microglial activation, and low‐density lipoprotein receptor‐related protein 1 (LRP1) expression in the prefrontal cortex and hippocampus following sleep deprivation and PTZ kindling. Furthermore, we observed a substantial deterioration in spatial working memory especially in the sleep‐deprived PTZ‐kindled group compared to the kindled group. Overall, our findings suggest that impairment of cognitive functions as seen in the sleep deprivation before kindling and sleep deprivation after kindling groups is attributable to a perturbation in the interaction between lipoproteins, their receptors, immune cells and their inflammatory/phagocytic responses impairing myelination/remyelination, thus aggravating cognitive deficits.

Synthesis and CNS Activity of Phenytoin Derivatives.

The derivatives of Phenytoin conjugated with various anilines were synthesized. The synthesized derivatives were evaluated for different physicochemical parameters along with log P values using different software programs to discover their ability to cross the blood brain barrier. The pharmacological activities such as antianxiety, skeletal muscle relaxant and anticonvulsant were evaluated by using different models. The new Phenytoin derivatives were synthesized and evaluated for different properties to predict CNS activity. The drugs synthesized by chloroacetylation and then different aniline were added to it. The compounds were evaluated for their different CNS activity by using different methods. The compounds were synthesized by firstly chloroacetylating the phenytoin and then different substituted anilines were added to it. The compounds were evaluated for antianxiety activity, muscle relaxant activity and anticonvulsant activity by using different models. The number of derivatives of Phenytoin was synthesized and various physicochemical parameters were optimized which revealed that the compound containing chloro groups such as C2 and C5 exhibited significant potential when compared with the standard drug Diazepam. It was portrayed that the synthesis, computational studies and evaluation of anticonvulsant, antianxiety and skeletal muscle relaxant activity of new Phenytoin derivatives were carried out. The compounds were productively synthesized and portrayed by molecular docking studies. The compounds also exhibit mild to moderate similarity with respect to standard drug. The synthesized drugs have the potential to be optimized further to engender new scaffolds to treat various CNS disorders.