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Antioxidant and Antiepileptic Activity of 1-[1-(3-Methoxyphenyl) (Tetralyl)] Piperidine as a New Derivative of Phencyclidine on Pentylentetrazole-Induced Kindling Mice

Document Type : Original Research

Authors

1 Neurophysiology Research Center, Shahed University, Tehran, Iran

2 Dept. of Chemistry, Faculty of Science, Islamic Azad University, Karaj Branch, Iran

3 Traditional Medicine Clinical Trial Research Center, Shahed University, Tehran, Iran

Abstract

Background and Objective: N-Methyl-D-aspartate (NMDA) antagonists such as piperidines are the most important antiepileptic drugs. Considering the fact that piperidine derivatives such as phencyclidine (PCP) and its new derivative, 1-[1-(3-methoxyphenyl) (tetralyl)] piperidine (PCP1), have different potencies, the antiepileptic effects of mentioned drugs were investigated in the present study.
Methods: Fifty male mice weighing 25-30 g were randomly selected and divided into five experimental groups: 1- Control 2- Pentylentetrazole-kindled mice, 3- Positive control group which received valproate, and groups 4 and 5, which received PCP and PCP1, respectively. Kindling was down by 11 periods injection of PTZ every second day for 22 days. At the 12th injection, all kindled group were tested for PTZ challenge dose. The exhibited phases of seizure (0-6) were observed and noted till 30 minutes after PTZ injection. Finally, the malondialdehyde, superoxide dismutase and nitric oxide levels of the animal’s brain tissues were determined and compared with others.
Results: PCP1 could have a prominent anti-convulsion effect compared to PCP, especially in the reduction of phase 2 duration time and seizure score in challenge dose. Our additional experiments showed that there was a significant reduction in NO level in PCP1 treated animals.
Conclusion: Administration of the new piperidine derivate, PCP1 could have yielded a prominent anti-convulsion effect in grand epilepsy. Regarding to the changes in conformation of PCP1 as a non-competitive antagonist of NMDA receptor, it may block the NMDA receptors potentially more effectively than phencyclidine.
 

Keywords

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Iranian Journal of Pathology
Volume 9, Issue 2 - Serial Number 2
April 2014
Pages 138-148
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History
  • Receive Date: 26 November 2012
  • Accept Date: 10 March 2013
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