Synthesis and study of anticonvulsant effect of 1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol as a new derivative of phencyclidine in PTZ-induced kindling model in male mice

Abstract

Background and Objective: Epilepsy is a common disease in communities. Since there is no cure for it and current treatments are not effective for every patient, new method for medical treatment of epileptic patients is necessary. As NMDA receptors antagonists are the most prominent anti-epileptic drugs, in this study we synthesized and investigated anti-epileptic effect of a new piperidine derivate 1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol as a new NMDA receptors antagonist in chemical kindling model. Materials and Methods: In this study, 48 male mice (NMRI), weighting 25-30 g, were selected and randomly divided into 4 groups (n=12 in each group). 1: PTZ 2: 1-[1-(4-Methoxyphenyl) (Cyclohexyl)] 3: piperidinol and 4: valproic acid (positive control). Chemical kindling was induced by PTZ (35 mg/kg, i.p.) injection 11 times one other days (for 22 days). In challenge dose at day 24, PTZ was applied at 75 mg/kg to the animals. Thirty minutes after PTZ injection, the animals were followed for convulsion scores (0-5). Finally, the mean of convulsion phases, threshold and duration of 2 and 5 phases were considered as data and the statistical analysis was done. Results: Data analysis showed that administration of the new piperidine derivate Methoxy-PCP has a prominent anticonvulsant effect than PCP, especially in reduction of phase 5 duration. Conclusion: The results suggest that administration of the new piperidine derivate, 1-[1-(4-Methoxyphenyl) (Cyclohexyl)] 4-piperidinol could yield a prominent anticonvulsant effect in epilepsy. Regarding changes in conformation of the new drug as a non-competitive antagonist, it may potentially block the NMDA receptors than other piperidine derivates.