scholarly journals Design, Synthesis, and Antidepressant Activity Study of Novel Aryl Piperazines Targeting Both 5-HT1A and Sigma-1 Receptors

2021 ◽  
Author(s):  
Yan-Na Ni ◽  
Xin-Li Du ◽  
Tao Wang ◽  
Yuan-Yuan Chen ◽  
Xiang-Qing Xu ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Metabolic Stability ◽  
Test Mouse ◽  
Design Synthesis ◽  
Sigma 1 Receptor ◽  
Piperazine Derivatives ◽  
Sigma 1

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.

scholarly journals Antidepressant-Like Activity of the Ethanolic Extract fromUncaria lanosaWallich var.appendiculataRidsd in the Forced Swimming Test and in the Tail Suspension Test in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lieh-Ching Hsu ◽  
Yu-Jen Ko ◽  
Hao-Yuan Cheng ◽  
Ching-Wen Chang ◽  
Yu-Chin Lin ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Antidepressant Drugs ◽  
Ethanolic Extract ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Probable Mechanism ◽  
Tail Suspension ◽  
Swimming Test ◽  
Mice Brain ◽  
Suspension Test

This study investigated the antidepressant activity of ethanolic extract ofU. lanosaWallich var.appendiculataRidsd (ULEtOH) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOHin FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOHexhibited antidepressant-like activity in FST and TST in mice. ULEtOHincreased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH. ULEtOHinhibited the activity of MAO-A. The amount of RHY in ULEtOHwas 17.12 mg/g extract. Our findings support the view that ULEtOHexerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOHmay be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

scholarly journals Anti-Depressant Activity of the Leaves of Zanthoxylum Armatum on Swiss Albino Mice

2020 ◽  
Vol 8 (02) ◽  
pp. 46-50
Author(s):  
Chandrajeet Kumar Yadav ◽  
Kamal Poudel ◽  
Roshan Mehta ◽  
Amit Kumar Shrivastava
Keyword(s):  
Methanolic Extract ◽  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Medical Problem ◽  
Mild Stress ◽  
Swiss Albino Mice ◽  
Zanthoxylum Armatum ◽  
Albino Mice

INTRODUCTION Depression is a global mental disorder that has high incidence, high recurrence, and high self-mutilation and suicide rates. Although the antidepressant drugs are available for the treatment, depression still continues to be a major medical problem. The present study was designed to study the anti-depressant activity of the leaves extract of Zanthoxylum armatum using forced swim test and tail suspension test (TST) on Swiss albino mice. MATERIAL AND METHODS The anti-depressant activity of the leaves of Zanthoxylum armatum was assessed using chronic unpredictable mild-stress (CUMS) induced depression in mice. The animals were treated with the methanolic extract of leaves of Zanthoxylum armatum orally at two doses of 100, 200 mg/kg body weight for eight days after (CUMS) induced depression in mice. RESULTS The data were analyzed by one-way ANOVA followed by tukey multiple comparison test. The leaves extract presented significant antidepressant activity in mice (p<0.05), CONCLUSION The results demonstrate that methanolic extract of leaves of Zanthoxylum armatum has got significant antidepressant activity.

scholarly journals Tail suspension test to evaluate the antidepressant activity of experimental drugs

2016 ◽  
Vol 11 (2) ◽  
pp. 292 ◽  
Author(s):  
Muhammad Aslam
Keyword(s):  
Forced Swimming Test ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Tail Suspension ◽  
Video Clips ◽  
Experimental Drugs ◽  
Behavioral Paradigm ◽  
Swimming Test ◽  
Suspension Test

<p>Tail suspension test (TST) is a common behavioral paradigm used to evaluate the antidepressant activity of experimental drugs. Like the forced swimming test, in this test the animals are set in an inescapable yet modestly distressing circumstance. In the tail suspension test, the extent of immobility is thought to be associated with the depressive-like condition of the animal and is significantly diminished by antidepressant drugs.</p><p><strong>Video clips</strong></p><p><a href="https://youtube.com/v/OqWrALPAGhA">Pre-experiment</a>:         53 sec</p><p><a href="https://youtube.com/v/T7sRbrn3xbQ">Experiment</a>:      7 min 31 sec</p><p> </p>

scholarly journals Influence of the endocannabinoid system on the antidepressant activity of bupropion and moclobemide in the behavioural tests in mice

2020 ◽  
Vol 72 (6) ◽  
pp. 1562-1572
Author(s):  
Ewa Poleszak ◽  
Sylwia Wośko ◽  
Karolina Sławińska ◽  
Elżbieta Wyska ◽  
Aleksandra Szopa ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Endocannabinoid System ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Cellular Level ◽  
Hplc Method ◽  
Receptor Function ◽  
Receptor Ligands ◽  
Behavioural Tests

Abstract Background Though there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated. Scientists have made attempts to develop novel therapeutical strategies to maximize effectiveness of therapy and minimize undesired reactions. One of the ideas is use of either dual-action agents or combined administration of two substances that affect diverse neurotransmissions. Thus, we investigated whether the selected CB receptor ligands (oleamide, AM251, JWH133, and AM630) can have an impact on the activity of bupropion and moclobemide. Bupropion belongs to the dual acting drugs, whereas moclobemide is an inhibitor of monoamine oxidase. Methods The mice forced swim test and the tail suspension test were applied in order to determine the potential antidepressant-like activity, whereas the HPLC method was used in order to assess the brain concentrations of the tested antidepressants. Results An intraperitoneal injection of sub-effective doses of oleamide (5 mg/kg), AM251 (0.25 mg/kg), and AM630 (0.25 mg/kg) increased activity of bupropion (10 mg/kg) in both behavioural tests. Effects of moclobemide (1.5 mg/kg) were potentiated only by AM251. These results were not influenced by the hypo- or hyperlocomotion of animals. Conclusion The outcomes of the present study revealed that particularly activation or inhibition of the CB1 receptor function may augment the antidepressant activity of bupropion, whereas only inhibition of the CB1 receptor function manages to increase activity of moclobemide. Most probably, an interplay between CB receptor ligands and bupropion or moclobemide takes place at the cellular level.

scholarly journals PHYTOCHEMICAL SCREENING AND ANTIDEPRESSANT ACTIVITY OF LEAVES EXTRACT OF DESMODIUM GANGETICUM

2021 ◽  
Vol 10 (2) ◽  
pp. 01-08
Author(s):  
Mr. Bablu Malviya ◽  
Mr. Narendra Patel ◽  
Dr.C.K. Tyagi ◽  
Dr. Prabhakar Budholiya
Keyword(s):  
Medicinal Plant ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Raw Material ◽  
Phytochemical Analysis ◽  
Medicinal And Aromatic Plants ◽  
Immobility Time ◽  
Chemical Studies ◽  
Powder Analysis

According to Biological Conservation Letter, more than 7,000 species of plants found in various ecosystems are said to be medicinal in the country. So, India is one of the world’s richest sources of medicinal and aromatic plants. Desmodium gangeticum is an important medicinal plant. It is commonly used in ayurvedic formulations for the treatment of various disorders. Phytochemical evaluations, pharmacogonostic evaluation, organoleptic characters, TLC profile was carried out to set them as diagnostic indices for the identification/validation of the raw material and standardization of the formulations. Preliminary phytochemical analysis showed the presence of active constituents which is necessary for the pharmacological activity. Organoleptic properties, phyto-chemical studies, powder analysis, showed the presence of adulteration in the powder. Majority of the antidepressant drugs improve depressive symptoms, but they exert multiple undesirable side effects. The search for more productive and well tolerated drugs is in progress. Phytochemical analysis of Desmodium gangeticum revealed the presence of alkaloids, phenols, flavonoids, Saponins, Steroids. Desmodium gangeticum is a well known medicinal plant as anti-inflammatory, antimicrobial and nephroprotective etc. It is a very good drug for urinogenital problems, hepatic problems, oxidative stress etc. The present study was depict to evaluate the antidepressant activity of hydroalcoholic extract of Desmodium gangeticum in mice. It was evaluated using the Tail Suspension Test (TST) and Forced Swimming Test (FST) in mice. Desmodium gangeticum (200 and 400 mg/kg) was administered orally in separate groups of Swiss albino mice weighing 20-25 for 14 days in TST and FST tests.. The Leaves extract of Desmodium gangeticum showed a dose dependant reduction in duration of immobility in mice. The dose of 400 mg/kg of Leaves extract of Desmodium gangeticum significantly reduced the immobility time of mice in both FST and TST. The effectual of extract was found to be similar to fluoxetine (20 mg mg/kg, po). It was found to be toxicologically safe with no deaths of mice when administered orally at the dose of 2000 mg/kg. From the current study, it can be concluded that the Leaves extract of Desmodium gangeticum possess dominant antidepressant activity as reveal by the TST and FST tests and is toxicologically safe.

scholarly journals Design, Synthesis and Characterization of HIV-1 CA-Targeting Small Molecules: Conformational Restriction of PF74

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 479
Author(s):  
Rajkumar Lalji Sahani ◽  
Raquel Diana-Rivero ◽  
Sanjeev Kumar V. Vernekar ◽  
Lei Wang ◽  
Haijuan Du ◽  
...  
Keyword(s):  
Small Molecules ◽  
Liver Microsomes ◽  
Imidazole Ring ◽  
Metabolic Stability ◽  
Binding Modes ◽  
Conformational Restriction ◽  
Design Synthesis ◽  
Antiviral Activities ◽  
Hiv 1

Small molecules targeting the PF74 binding site of the HIV-1 capsid protein (CA) confer potent and mechanistically unique antiviral activities. Structural modifications of PF74 could further the understanding of ligand binding modes, diversify ligand chemical classes, and allow identification of new variants with balanced antiviral activity and metabolic stability. In the current work, we designed and synthesized three series of PF74-like analogs featuring conformational constraints at the aniline terminus or the phenylalanine carboxamide moiety, and characterized them using a biophysical thermal shift assay (TSA), cell-based antiviral and cytotoxicity assays, and in vitro metabolic stability assays in human and mouse liver microsomes. These studies showed that the two series with the phenylalanine carboxamide moiety replaced by a pyridine or imidazole ring can provide viable hits. Subsequent SAR identified an improved analog 15 which effectively inhibited HIV-1 (EC50 = 0.31 μM), strongly stabilized CA hexamer (ΔTm = 8.7 °C), and exhibited substantially enhanced metabolic stability (t1/2 = 27 min for 15 vs. 0.7 min for PF74). Metabolic profiles from the microsomal stability assay also indicate that blocking the C5 position of the indole ring could lead to increased resistance to oxidative metabolism.

scholarly journals An Insight into the Anxiolytic and Antidepressant-Like Proprieties of Carum carvi L. and Their Association with Its Antioxidant Activity

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 207 ◽  
Author(s):  
Imane Es-safi ◽  
Hamza Mechchate ◽  
Amal Amaghnouje ◽  
Fatima Zahra Jawhari ◽  
Omkulthom Mohamed Al Kamaly ◽  
...  
Keyword(s):  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Behavioral Model ◽  
Antioxidant Property ◽  
Professional Lives ◽  
Traditional Use ◽  
Antioxidant Power ◽  
Carum Carvi ◽  
Polyphenolic Extract

Depression and anxiety are widespread illnesses whose consequences on patients’ social and professional lives are becoming ever more dangerous and severe. The study’s objective is to explore the antidepressant-like and anxiolytic activity of the polyphenolic extract of Carum carvi L. as well as its antioxidant power as they were recently associated. The predictive antidepressant activity was evaluated using the forced swimming and tail suspension test in mice, a preclinical behavioral model widely used to determine the efficacy of antidepressant drugs. As for anxiolytic-like activity, two models were used, namely the light/dark chamber test to measure the animal’s degree of anxiety and the open field test to evaluate both anxiolytic and locomotor activity. The tests results indicate a remarkable antidepressant and anxiolytic-like effect after oral administration of the polyphenolic fraction of C. carvi and interesting antioxidant property. In the extract it has been confirmed the presence of 6 molecules belonging to polyphenols, identified with HPLC analysis. This study confirms and encourages the traditional use of the extract and appeals to further studies to understand its action mechanism.

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