| Abstrakt: |
Introduction: Epilepsy is one of the most common brain conditions. 1,3,4-oxadiazole and N-phenylacetamide, are found in anticonvulsant agents that acted via benzodiazepine (BZD) receptor. In this study we evaluated the anticonvulsant properties of some new 2-phenoxyphenyl-1,3,4-oxadiazole-N-phenylacetamid derivatives. Methods and Materials: A new series of 2-phenoxyphenyl-1,3,4-oxadiazole-N-phenylacetamid derivatives C1- 13 have been designed based on reported BZD receptor agonists and synthesized by simple chemical reactions. These compounds evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice. Flumazenil as a standard antagonist against BZD receptor was used for understanding the possible mechanism of the most potent compound. For further investigation of interaction of the most potent compounds in BZD receptor, molecular modeling was performed by Autodock (1.5.6) software. Also neurotoxicity was evaluated by rotarod test. Results: The results of pharmacological studies showed that target compounds especially were active in MES seizure. The most potent compounds were nitro derivatives C5 and C4. Whereas in PTZ model the majority of them were inactive except 4-nitro derivative C4 and 4-bromo derivative C1 with mild protection. Flumazenil test on C5 demonstrated that anticonvulsant activity of the latter compound was completely reversed. In docking analysis, C5 and C4 showed important interactions at the BZD-binding site of GABAA receptor compared with diazepam. Furthermore, neurotoxicity of the latter compounds was lower than positive control diazepam. Conclusion: The designed compounds have good potential for further evaluations as new anticonvulsant agents. [ABSTRACT FROM AUTHOR] |
