scholarly journals CARBAMAZEPINE LOADED VESICULAR STRUCTURES FOR ENHANCED BRAIN TARGETING VIA INTRANASAL ROUTE: OPTIMIZATION, IN VITRO EVALUATION, AND IN VIVO STUDY

2019 ◽  
pp. 264-274 ◽  
Author(s):  
GHADA E. YASSIN ◽  
REHAM I. AMER ◽  
AHMED M. FAYEZ
Keyword(s):  
Elevated Plus Maze ◽  
Physical Stability ◽  
Intranasal Route ◽  
Vesicular Structure ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
The Brain

Objective: Carbamazepine (CBZ) is used as a first line in the treatment of grand mal and partial seizures, but it suffers from many side effects on different systems of the body. The objective of the present study was optimization of CBZ vesicular structures using 23 multifactorial design for the most efficient targeting of CBZ to the brain via the intranasal route. Methods: The concentration of CBZ (10 and 20%), type of vesicles (niosomes and spanlastics) and speed of rotation (200 and 300 rpm) were considered as the independent variables XA, XB and XC respectively, while the dependent variables were particle size PS (Y1), polydispersity index PDI (Y2), zeta potential ZP (Y3) and entrapment efficiency EE (Y4). The study of the effect of different formulation variables was carried out using Design-Expert ® software. CBZ-loaded spanlastics and noisome were prepared by the ethanol injection method and thin film hydration method, respectively. The optimized formulation was subjected to viscosity measurement, in vitro drug release and physical stability studies. In vivo evaluations in rats for the optimized formulation in comparison to oral CBZ suspension was carried out using behavioral assessment by elevated plus maze test, determination of endothelial nitric oxide synthase (e-NOS), reduced glutathione (GSH) and ELISA estimation of TNFα. Results: The selected optimized formulation (F0) containing 20% CBZ and spanlastic vesicular structure showed PS, PDI, ZP, and the EE % of 350.09 nm, 0.830, 16.124mV and 82.777%, respectively. In vitro release study of F0 demonstrated the ability of the F0 to increase drug release in the range time from 10-60 min (p<0.05) when compared with CBZ suspension. The viscosity of F0 was nearly uniform (65 cps). The photomicrograph taken by the transmission electron microscopy (TEM) reveals the spherical shape of F0. Good physical stability for six months of storage at 25˚ C was found for F0. The optimized spanlastic formulation F0 showed a decrease in latency time in behavior assessment test using elevated plus Maze test, a decrease in serum eNOS and TNF-α and increase in GSH when compared with the oral CBZ suspension, in addition to the histopathological study that revealed the more CBZ uptake by the brain. Conclusion: The optimized spanlastic formulation F0 achieved better results when compared with the oral CBZ suspension for targeting the CBZ spanlastics vesicular structure to the brain via the nasal route.

scholarly journals N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 349
Author(s):  
Agnieszka A. Kaczor ◽  
Katarzyna M. Targowska-Duda ◽  
Andrea G. Silva ◽  
Magda Kondej ◽  
Grażyna Biała ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Elevated Plus Maze ◽  
G Protein Coupled Receptors ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Antipsychotic Activity ◽  
Plus Maze ◽  
G Protein Coupled

N-(2-hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol -1-yl)propyl]piperidine-4-carboxamide (D2AAK4) is a multitarget ligand of aminergic G protein-coupled receptors (GPCRs) identified in structure-based virtual screening. Here we present detailed in vitro, in silico and in vivo investigations of this virtual hit. D2AAK4 has an atypical antipsychotic profile and low affinity to off-targets. It interacts with aminergic GPCRs, forming an electrostatic interaction between its protonatable nitrogen atom and the conserved Asp 3.32 of the receptors. At the dose of 100 mg/kg D2AAK4 decreases amphetamine-induced hyperactivity predictive of antipsychotic activity, improves memory consolidation in passive avoidance test and has anxiogenic properties in elevated plus maze test (EPM). Further optimization of the virtual hit D2AAK4 will be aimed to balance its multitarget profile and to obtain analogs with anxiolytic activity.

scholarly journals Investigation of the Pharmacological Properties of Lepidagathis hyalina Nees through Experimental Approaches

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Fowzul Islam Fahad ◽  
Niloy Barua ◽  
Md. Shafiqul Islam ◽  
Syed Al Jawad Sayem ◽  
Koushik Barua ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Tail Suspension Test ◽  
Clot Lysis ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Swimming Test ◽  
Dose Dependent

Lepidagathis hyalina Nees is used locally in Ayurvedic medicine to treat coughs and cardiovascular diseases. This study explored its pharmacological potential through in vivo and in vitro approaches for the metabolites extracted (methanolic) from the stems of L. hyalina. A qualitative phytochemical analysis revealed the presence of numerous secondary metabolites. The methanol extract of L. hyalina stems (MELHS) showed a strong antioxidative activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assays, and in the quantitative (phenolic and flavonoid) assay. Clot lysis and brine shrimp lethality bioassays were applied to investigate the thrombolytic and cytotoxic activities, respectively. MELHS exhibited an expressive percentage of clot lysis (33.98%) with a moderately toxic (115.11 μg/mL) effect. The in vivo anxiolytic activity was studied by an elevated plus maze test, whereas the antidepressant activity was examined by a tail suspension test and forced swimming test. During the anxiolytic evaluation, MELHS exhibited a significant dose-dependent reduction of anxiety, in which the 400 mg/kg dose of the extract showed 78.77 ± 4.42% time spent in the open arm in the elevated plus maze test. In addition, MELHS demonstrated dose-dependent and significant activities in the tail suspension test and forced swimming test, whereas the 400 mg/kg dose of the extract showed 87.67 ± 6.40% and 83.33 ± 6.39% inhibition of immobile time, respectively. Therefore, the current study suggests that L. hyalina could be a potential source of anti-oxidative, cytotoxic, thrombolytic, anxiolytic, and antidepressant agents. Further study is needed to determine the mechanism behind the bioactivities.

Anticonvulsant, Anxiolytic and Antidepressant Properties of the β-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems

2020 ◽  
Vol 14 (1) ◽  
pp. 36-51 ◽  
Author(s):  
George L. da Silva Oliveira ◽  
José C. Correia L. da Silva ◽  
Ana P. dos Santos C. L da Silva ◽  
Chistiane M. Feitosa ◽  
Fernanda R. de Castro Almeida
Keyword(s):  
Receptor Antagonist ◽  
Molecular Mechanisms ◽  
Elevated Plus Maze ◽  
Feeding Test ◽  
Swiss Mice ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Gabaergic Receptors ◽  
Pre Treatment

Background: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with β-caryophyllene is still little discussed. Objectives: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of β-caryophyllene (β-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. Methods: This study evaluated the neurobehavioral effects of β-CBP using the open field test, rota-rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. Results:: The results demonstrated that the neuropharmacological activities of β-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of β-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of β-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500- 750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of β-CBP. Conclusion: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of β-CBP in female Swiss mice.

scholarly journals Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hirotaka Shoji ◽  
Tsuyoshi Miyakawa
Keyword(s):  
Elevated Plus Maze ◽  
Plasma Corticosterone ◽  
Illumination Level ◽  
Test Battery ◽  
Lower Percentage ◽  
Behavioral Tests ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Corticosterone Response

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.

Anxiety levels and wild running susceptibility in rats: assessment with elevated plus maze test and predator odor exposure

2005 ◽  
Vol 68 (2) ◽  
pp. 135-144 ◽  
Author(s):  
Hugo Medeiros Garrido de Paula ◽  
Amauri Gouveia ◽  
Marcos Vinícius de Almeida ◽  
Katsumasa Hoshino
Keyword(s):  
Elevated Plus Maze ◽  
Predator Odor ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Anxiety Levels ◽  
Odor Exposure
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