Synthesis and Study of Anti-convulsive Effect of 1-[1-(4-Methylphenyl) (Cyclohexyl)] 4-piperidinol as a New Derivative of Phencyclidine by PTZ- Induced Kindling Model in Male Mice

Abstract

Background and Objective: Regarding the prevalence of epilepsy in human society and with respect to insufficiency of usual treatments, new strategies and methods for medical treatment of epileptic patients are necessary. As NMDA receptor antagonists are the most prominent anti-epileptic drugs, in the present study, we synthesized and investigated anti-epileptic effect of a new piperidine derivates 1-[1-(4-Methylphenyl) (Cyclohexyl)] 4- piperidinol as a new NMDA receptor antagonist in chemical kindling model. Materials and Methods: Sixty male mice (NMRI), weighing 25-30 g, were selected and randomly divided into 5 groups (n=12 in each group). 1: PTZ 2: 1-[1-(Phencyclohexyl) piperidine, PCP)] 3: 1-[(1-3-Methoxy phenyl tetralyl) piperidine)] 4: 1-[1-(4-Methylphenyl) (Cyclohexyl)] 4- piperidinol and 5: valproic acid (positive control). Chemical kindling was induced by PTZ (35 mg/kg, i.p) injection, 11 times on alternate days (22 days). In final injection (challenge dose) at 24th day, PTZ were applied with 75 mg/kg to the animals. Thirty minutes after PTZ injection, the animals were followed for convulsion scores (0-5). Results: Data analysis showed that administration of 1-[1-(4-Methylphenyl) (Cyclohexyl)] 4- piperidinol has a prominent anti-convulsion effect versus PCP, especially in reduction of phase 2 duration. Meanwhile, this compound had a marked anti-epileptic effect in challenge dose. Conclusion: The results suggest that administration of the new piperidine derivate, 1-[1-(4-Methylphenyl) (Cyclohexyl)] 4- piperidinol could yield a prominent anti-convulsion effect in grand mal epilepsy. Regarding changes of its conformation as a non-competitive antagonist, it may block the NMDA receptors more powerfully than other piperidine derivates.