scholarly journals Design, synthesis and anticonvulsant-analgesic activity of new N-[(phenoxy)alkyl]- and N-[(phenoxy)ethoxyethyl]aminoalkanols

MedChemComm ◽  
2017 ◽  
Vol 8 (1) ◽  
pp. 220-238 ◽  
Author(s):  
Anna Rapacz ◽  
Anna M. Waszkielewicz ◽  
Katarzyna Pańczyk ◽  
Karolina Pytka ◽  
Paulina Koczurkiewicz ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
Anticonvulsant Activity ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Design Synthesis ◽  
Electroshock Seizure Threshold

New aminoalkanols have been synthesized and evaluated for their anticonvulsant activity in maximal electroshock (MES), maximal electroshock seizure threshold (MEST) and pentylenetetrazol (PTZ) tests, and show promising activity.

Synthesis and Anticonvulsant Activity of α-Amino Acid Amide Derivatives

2019 ◽  
Vol 15 (5) ◽  
pp. 547-561
Author(s):  
Valerie Currier ◽  
Maryam Molki ◽  
Katelyn Fryman ◽  
Lacey D. Rodgers ◽  
A. Michael Crider
Keyword(s):  
Amino Acid ◽  
Side Effects ◽  
Anticonvulsant Activity ◽  
Acid Amide ◽  
New Drugs ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Maximal Electroshock Seizure Test ◽  
Amide Derivatives

Background: Epilepsy is a disease of the central nervous system that affects approximately 50 million individuals worldwide. Although several new drugs have been marketed in the last 25 years, almost one-third of patients are not protected. In many cases, currently available drugs produce undesirable side effects. As a result, a need exists for novel anticonvulsants with unique mechanisms of action and minimal side effects. Methods: A mixed anhydride coupling procedure and standard deprotection procedures were utilized to prepare 36 α-amino acid amides. All final products were evaluated in mice and rats utilizing a standard battery of anticonvulsant tests. Results: α-Amino acids containing a 2,6-dimethylanilide group exhibited anticonvulsant activity in the maximal electroshock seizure test and 6 Hz test in mice and rats. A small, branched-chain on the α- carbon generally maintained or enhanced anticonvulsant activity in the maximal electroshock seizure test. The (R)-α-amino acid amides were typically more potent and slightly more neurotoxic than the corresponding (S)-enantiomers. The valine dimethylanilide (R)-42 was highly active in the MES test in mice (ED50 = 3.6mg/kg) and rats (ED50 = 3.8 mg/kg). (R)-42 also demonstrated excellent anticonvulsant activity in the 6 Hz, picrotoxin, and corneal kindled mouse tests. Furthermore, (R)-42 did not lower seizure threshold when evaluated in the intravenous metrazol seizure test. Conclusion: α-Amino acid 2,6-dimethylanilides exhibited potent activity in a variety of anticonvulsant tests in mice and rats. The valine derivative (R)-42 represents a promising compound for potential use in complex partial seizures.

Mouse strain variation in maximal electroshock seizure threshold

2002 ◽  
Vol 936 (1-2) ◽  
pp. 82-86 ◽  
Author(s):  
Thomas N. Ferraro ◽  
Gregory T. Golden ◽  
George G. Smith ◽  
Denis DeMuth ◽  
Russell J. Buono ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Strain Variation ◽  
Maximal Electroshock Seizure ◽  
Electroshock Seizure Threshold

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.

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