Novel Derivatives of Phthalimide With Potent Anticonvulsant Activity in Ptz and Mes Seizure Models Publisher



Davood A¹ ; Iman M^{2, 3} ; Pouriaiee H⁴ ; Shafaroodi H⁵ ; Akhbari S¹ ; Azimidoost L¹ ; Imani E¹ ; Rahmatpour S¹ Show Affiliations
Source: Iranian Journal of Basic Medical Sciences Published:2017

Abstract

Objective(s): Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents. Materials and Methods: Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models. Results: The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore. Conclusion: Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures. © 2017, Mashhad University of Medical Sciences. All rights reserved.