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.

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.

Effects of amlodipine, diltiazem, and verapamil on the anticonvulsant action of topiramate against maximal electroshock-induced seizures in micePresented in part at the 11th Congress of the European Federation of Neurological Societies, Brussels, Belgium, 25–28 August 2007.

2008 ◽  
Vol 86 (3) ◽  
pp. 113-121 ◽  
Author(s):  
Jarogniew J. Luszczki ◽  
Michal K. Trojnar ◽  
Marcin P. Trojnar ◽  
Zaneta Kimber-Trojnar ◽  
Beata Szostakiewicz ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
European Federation ◽  
Maximal Electroshock ◽  
Calcium Channel Antagonists ◽  
Maximal Electroshock Seizure ◽  
Experimental Animals ◽  
Anticonvulsant Action ◽  
Mes Test ◽  
Total Brain ◽  
New Generation

To assess the effect of 3 calcium channel antagonists (amlodipine, diltiazem, and verapamil) on the anticonvulsant action of topiramate (a new generation antiepileptic drug) in the mouse maximal electroshock seizure (MES) model. Amlodipine (20 mg/kg) significantly enhanced the anticonvulsant activity of topiramate in the MES test in mice, reducing its ED50 value from 54.83 to 33.10 mg/kg (p < 0.05). Similarly, diltiazem (5 and 10 mg/kg) markedly potentiated the antiseizure action of topiramate against MES, lowering its ED50 value from 54.83 to 32.48 mg/kg (p < 0.05) and 28.68 mg/kg (p < 0.01), respectively. In contrast, lower doses of amlodipine (5 and 10 mg/kg) and diltiazem (2.5 mg/kg) and all doses of verapamil (5, 10, and 20 mg/kg) had no significant impact on the antiseizure action of topiramate. Pharmacokinetic verification of the interaction of topiramate with amlodipine and diltiazem revealed that neither amlodipine nor diltiazem affected total brain topiramate concentration in experimental animals, and thus, the observed interactions were concluded to be pharmacodynamic in nature. The favorable combinations of topiramate with amlodipine or diltiazem deserve more attention from a clinical viewpoint because the enhanced antiseizure action of topiramate was not associated with any pharmacokinetic changes in total brain topiramate concentration.

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.

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.

scholarly journals New TRPV1 Antagonists as Candidates for Effective Anticonvulsant and Antinociceptive Agents

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 30
Author(s):  
Kamiński ◽  
Jakubiec ◽  
Zagaja ◽  
Andres-Mach ◽  
Mogilski ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Epileptic Seizures ◽  
Maximal Electroshock ◽  
Neurogenic Pain ◽  
Mes Test ◽  
Trpv1 Receptors ◽  
Seizure Models ◽  
The Common ◽  
Drug Resistant Epilepsy ◽  
Patients With Epilepsy

Epilepsy is recognized as one of the most common neurological disorders with a high risk of drug resistance. Notably, about one-third of the patients with epilepsy are not responsive to pharmacological treatment. Thus, the search for new, more effective anticonvulsants with a novel mechanism of action is undoubtedly necessary. The most recent neurobiological studies implicate central TRPV1 receptors in the induction of epileptic seizures. Moreover, it is suggested that TRPV1 desensitization is one of the crucial mechanisms of action responsible for the anticonvulsant activity of cannabidiol (CBD), which was proven to be effective against drug-resistant epilepsy. Bearing in mind the aforementioned facts, we developed in our recent studies a series of chemically original TRPV1 antagonists. Their structures were designed as integrated hybrids that join on the common chemical template the structural fragments of anticonvulsants identified by our team in the previous studies and known TRPV1 antagonists (described in the literature). As a result, these compounds revealed potent anticonvulsant activity in the preclinical studies using the most widely employed animal seizure models, namely, the maximal electroshock (MES) test, and the psychomotor 6 Hz (32 mA and 44 mA) seizure model in mice. In addition, selected substances demonstrated potent effectiveness by decreasing pain responses in formalin-induced tonic pain, in capsaicin-induced neurogenic pain, as well as in oxaliplatin-induced neuropathic pain in mice.

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 Anticonvulsant Effects of Aerial Parts of Verbena officinalis Extract in Mice: Involvement of Benzodiazepine and Opioid Receptors

2017 ◽  
Vol 22 (4) ◽  
pp. 632-636 ◽  
Author(s):  
Amir Rashidian ◽  
Fatemeh Kazemi ◽  
Saeed Mehrzadi ◽  
Ahmad Reza Dehpour ◽  
Shahram Ejtemai Mehr ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Hind Limb ◽  
Ethanolic Extract ◽  
Maximal Electroshock ◽  
Dependent Manner ◽  
Reference Drug ◽  
Mes Test ◽  
Aerial Parts ◽  
Tonic Extension ◽  
Dose Dependent

To evaluate the anticonvulsant activity of the aerial parts of Verbena officinalis used traditionally by local Iranians for the treatment of convulsion. The anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Diazepam was used as reference drug. In addition, for investigating the mechanism of V officinalis in PTZ model, flumazenil and naloxone were injected before V officinalis. The extract showed no toxicity and significantly increased the period taken before the onset and decreased the duration of the seizures induced by PTZ. In the MES test, V officinalis displayed significant reduction in hind limb tonic extension duration in a dose-dependent manner. The results propose that V officinalis ethanolic extract has anticonvulsant activity against seizure. It seems that these effects may be related to potentiating of GABAergic system. Moreover, this study supports the use of this plant by local Iranians in order to treat convulsion.

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