Synthesis and Pharmacological Evaluation of New Indolyl-oxadiazoles as Anticonvulsant Agents

2009 ◽  
Vol 2 (3) ◽  
pp. 661-666
Author(s):  
Harish Rajak ◽  
Ravichandran Veerasamy ◽  
Arun Kumar Gupta ◽  
Murli Dhar Kharya ◽  
Pradeep Mishra
Keyword(s):  
1H Nmr ◽  
13C Nmr ◽  
Anticonvulsant Activity ◽  
Anticonvulsant Drug ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Anticonvulsant Agents ◽  
Pharmacological Evaluation ◽  
Anticonvulsant Activities

The search for better anticonvulsant drug and the importance of 2,5-disubstituted 1,3,4-oxadiazoles and indole as anticonvulsant pharmacophores, prompted us to design, synthesize and evaluate a series of differently substituted 1,3,4-oxadiazoles for their potential anticonvulsant activity. The structures of the compounds were elucidated by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analyses. Most of the test compounds demonstrated appreciable anticonvulsant activities in maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models.

Synthesis and Anticonvulsant Activity of 3-(alkylamino, alkoxy)-1,3,4,5- Tetrahydro-2H-benzo [b] azepine-2-one Derivatives

2018 ◽  
Vol 17 (6) ◽  
pp. 448-457 ◽  
Author(s):  
Xia Huang ◽  
Tie Chen ◽  
Rong-Bi Han ◽  
Feng-Yu Piao
Keyword(s):  
1H Nmr ◽  
Elemental Analysis ◽  
13C Nmr ◽  
Anticonvulsant Activity ◽  
Mass Spectra ◽  
Maximal Electroshock ◽  
Test Compound ◽  
Maximal Electroshock Test ◽  
Mes Test ◽  
Structure Activity

Background & Objective: A series of novel 3-Substituted-1,3,4,5-Tetrahydro-2H-benzo [b] azepine-2-one Derivatives (4, 5, 7, 10, 12, 5a-j, 8a-e) were synthesized from 1,2,3,4-Tetrahydro-1- naphthalenone. The structures of these compounds were confirmed by IR, 1H NMR, 13C NMR, MASS spectra and elemental analysis. Their anticonvulsant activity was evaluated by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. Compound 4 showed the maximum anticonvulsant activity against the maximal electroshock test (ED50=26.4, PI =3.2) and against the subcutaneous pentylenetetrazol test (ED50=40.2, PI =2.1). Conclusion: Possible structure-activity relationship was discussed.

A quantitative structure-activity relationship study for α-substituted acetamido-N-benzylacetamide derivatives — A novel anticonvulsant drug class

2005 ◽  
Vol 83 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Albert Y Jin ◽  
Harold Kohn ◽  
Cécile Béguin ◽  
Shridhar V Andurkar ◽  
James P Stables ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Anticonvulsant Drug ◽  
Wiener Index ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Maximal Electroshock ◽  
Least Squares Regression ◽  
Maximal Electroshock Seizure ◽  
Information Index ◽  
Mes Test

A library of 35 benzylacetamide derivatives was evaluated for anticonvulsant activity as reflected in the ED50 (mg/kg) required to suppress seizure activity in the maximal electroshock seizure (MES) test. Using the method of partial least-squares regression in conjunction with cross-validation, the influence of 31 topological, electronic, physico chemical, and structural properties on anticonvulsant activity was investigated. A QSAR model of the logED50 in the MES test was established (R2adj = 0.77) as a function of the following seven properties: the Wiener index on distance code (Wmean), the mean information index on atomic composition (rIac), the partial charge at the C-terminal carbonyl carbon (qCC), the sum of partial charges in the α substituent (qαtotal), the number of hydrogen bond donors and acceptors in the α substituent (Hdα and Haα), and the calculated value of the squared n-octanol/water partition coefficient. Based on this model, two new amido ketone compounds — (R,S)-2-acetamido-5-phenyl-3-pentanone and cis/trans-(R,S)-2-acetamido-5-phenyl-4-penten-3-one — were synthesized and shown to have significant anticonvulsant activity in the MES test.Key words: QSAR, anticonvulsant, benzylacetamide, functionalized amino acid, amido ketones.

scholarly journals Synthesis, Anticonvulsant and Neurotoxicity Screening of Some Novel 2, 5-Disubstituted - 1, 3, 4 � Oxadiazole Derivatives

2017 ◽  
Vol 9 (01) ◽  
Author(s):  
Y. Khatoon ◽  
M. Shaquiquzzaman ◽  
V. Singh ◽  
M. Sarafroz
Keyword(s):  
Sodium Hydroxide ◽  
1H Nmr ◽  
Elemental Analysis ◽  
Neurological Deficit ◽  
Anticonvulsant Activity ◽  
Sodium Hydroxide Solution ◽  
Maximal Electroshock ◽  
Rota Rod Test ◽  
Oxadiazole Derivatives ◽  
Ft Ir

A series of 2, 5-disubstituted - 1, 3, 4 oxadiazoles (4a-o) were synthesized on refluxing hydrazine carbothioamides with iodine and potassium iodide in ethanolic sodium hydroxide solution starting from methyl-3-amino-4-hydroxy benzoate via synthesis of an intermediate methyl-2-substitutedaryl-1, 3-benzoxazole-5-carboxylates and 2-substitutedaryl-1, 3-benzoxazole-5-carbohydrazides. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H-NMR, MS) and elemental analysis. All these compounds were screened for anticonvulsant activity using Maximal Electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) method. Anticonvulsant activity was shown by majority of the synthesized compounds when given i.p. to mice. Among the tested compounds 4e, 4j and 4o were considered to have potent anticonvulsant activity comparable to that of standard drugs Phenytoin and Carbamazepine. Compounds 4e, 4g, 4h, 4i, 4k and 4m passed the rota rod test successfully without any sign of neurological deficit.

Design, Synthesis and Biological Activity of Some 4, 5-Disubstituted-2, 4- Dihydro-3H-1, 2, 4- Triazole-3-Thione Derivatives

2019 ◽  
Vol 19 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Krishan Kumar Verma ◽  
Umesh Kumar Singh ◽  
Jainendra Jain
Keyword(s):  
Biological Activity ◽  
1H Nmr ◽  
Anticonvulsant Activity ◽  
Maximal Electroshock ◽  
Gamma Amino Butyric Acid ◽  
Rotarod Test ◽  
Design Synthesis ◽  
Amino Butyric Acid ◽  
Mes Test ◽  
Autodock 4.2

Background: In the present study, 4, 5-disubstituted triazol-3-thione derivatives were synthesized and evaluated for anticonvulsant activity along with neurotoxicity determination. Materials and Methods: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The anticonvulsant activity was assessed by Maximal Electroshock (MES) test and subcutaneous Pentylenetetrazole (scPTZ) tests and neurotoxicity was assessed by rotarod test. Docking was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. Results: The compounds 7a and 9a with significant pharmacological activity were also found to interact with LYS329 residue of GABA-AT by H-bond with a docking score of -5.92 kcal/mol (Ki = 41.99 μM) and -5.87 kcal/mol (Ki = 49.83 μM) respectively. Conclusion: Most of the compounds were found to be active in MES test but only seven showed protection in scPTZ test.

Evaluation of the Anticonvulsant Activity of Terpinen-4-ol

2009 ◽  
Vol 64 (1-2) ◽  
pp. 1-5 ◽  
Author(s):  
Damião P. de Sousa ◽  
Franklin F. F. Nóbrega ◽  
Liana C. S. L. de Morais ◽  
Reinaldo N. de Almeida
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Animal Models ◽  
Motor Activity ◽  
Anticonvulsant Activity ◽  
Maximal Electroshock ◽  
Aromatic Plants ◽  
Depressant Effect ◽  
Maximal Electroshock Seizure ◽  
The Central Nervous System

Terpinen-4-ol is a monoterpenoid alcohol and component of the essential oils of several aromatic plants. Similarly to terpinen-4-ol, other monoterpenoid alcohols have shown anticonvulsant activity in convulsion animal models. The present study aimed to investigate the anticonvulsant activity of terpinen-4-ol. Treatment of mice with terpinen-4-ol ( 200 mg/kg) caused a signifi cant decrease in the spontaneous motor activity at 30, 60 and 120 min after administration. Terpinen-4-ol (100 and 200 mg/kg) produced a significant dosedependent increase in the duration of sleeping in mice. Pretreatment of mice with terpinen-4- ol at doses of 100, 200 and 300 mg/kg significantly increased the latency of pentylenetetrazole -induced convulsions. Terpinen-4-ol (200 and 300 mg/kg) also inhibited the induced seizures of picrotoxin. In another model, maximal electroshock seizure, terpinen-4-ol decreased the tonic hind convulsions percentage at the dose of 300 mg/kg. From the overall results we can conclude that terpinen-4-ol showed a depressant effect on the central nervous system and significant anticonvulsant activity.

Synthesis and Evaluation of N-substituted (Z)-5-(Benzo[d][1,3]dioxol-5- ylmethylene)-2-Thioxothiazolidin-4-one Derivatives and 5-Substituted- Thioxothiazolidindione Derivatives as Potent Anticonvulsant Agents

2020 ◽  
Vol 18 (10) ◽  
pp. 798-807
Author(s):  
Shiyang Dong ◽  
Yanhua Liu ◽  
Jun Xu ◽  
Yue Hu ◽  
Limin Huang ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Structural Modification ◽  
Docking Study ◽  
Maximal Electroshock ◽  
Molecular Docking Study ◽  
Rotarod Test ◽  
Protective Index ◽  
Channel Inhibition ◽  
Anticonvulsant Activities

Background: Epilepsy is a serious and common neurological disorder threatening the health of humans. Despite enormous progress in epileptic research, the anti-epileptic drugs present many limitations. These limitations prompted the development of more safer and effective AEDs. Methods: series of N-substituted (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)- 2-thioxothiazolidin-4- one derivatives and 5-substituted-thioxothiazolidindione derivatives were designed, synthesized and tested for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ). Neurotoxicity was determined by the rotarod test. Results: Among them, the most potent 4e displayed high protection against MES-induced seizures with an ED50 value of 9.7 mg/kg and TD50 value of 263.3 mg/kg, which provided 4e with a high protective index (TD50/ED50) of 27.1 comparable to reference antiepileptic drugs. 4e clearly inhibits the NaV1.1 channel in vitro. The molecular docking study was conducted to exploit the results. Conclusion: Stiripentol is a good lead compound for further structural modification. Compound 4e was synthesized, which displayed remarkable anticonvulsant activities, and the NaV1.1 channel inhibition was involved in the mechanism of action of 4e.

Captopril potentiates the anticonvulsant activity of carbamazepine and lamotrigine in the mouse maximal electroshock seizure model

2010 ◽  
Vol 117 (10) ◽  
pp. 1161-1166 ◽  
Author(s):  
Krzysztof Łukawski ◽  
Tomasz Jakubus ◽  
Grzegorz Raszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Anticonvulsant Activity ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Seizure Model

scholarly journals STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

2019 ◽  
Vol 12 (1) ◽  
pp. 185
Author(s):  
Shipra Kaushik ◽  
Kalpana Gohain
Keyword(s):  
Normal Saline ◽  
Anticonvulsant Activity ◽  
Ethanolic Extract ◽  
Albino Rats ◽  
Acorus Calamus ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Onset Of Action ◽  
Electrical Shock ◽  
Seizure Models

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

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