Premium
Synthesis and Evaluation of Antidepressant‐like Activity of Some 4‐Substituted 1‐(2‐methoxyphenyl)Piperazine Derivatives
Author(s) -
Waszkielewicz Anna M.,
Pytka Karolina,
Rapacz Anna,
Wełna Elżbieta,
Jarzyna Monika,
Satała Grzegorz,
Bojarski Andrzej,
Sapa Jacek,
Żmudzki Paweł,
Filipek Barbara,
Marona Henryk
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12394
Subject(s) - piperazine , tail suspension test , imipramine , chemistry , receptor , in vivo , serotonergic , 5 ht receptor , pharmacology , behavioural despair test , serotonin , antidepressant , ed50 , stereochemistry , biochemistry , medicine , biology , organic chemistry , alternative medicine , microbiology and biotechnology , pathology , hippocampus
A series of new derivatives of N ‐(2‐methoxyphenyl)piperazine have been synthesized for their affinity toward serotonergic receptors and for their potential antidepressant‐like activity. They have been evaluated toward receptors 5‐HT 1A , 5‐HT 6 , and 5‐HT 7 , as well as in vivo in the tail suspension, locomotor activity, and motor co‐ordination tests. All the tested compounds proved very good affinities toward 5‐HT 1A and 5‐HT 7 receptors. The most promising compound was 1‐[(2‐chloro‐6‐methylphenoxy)ethoxyethyl]‐4‐(2‐methoxyphenyl)piperazine hydrochloride, exhibiting affinity toward receptors K i <1 n m (5‐HT 1A ) and K i = 34 n m (5‐HT 7 ). Antidepressant‐like activity (tail suspension test) was observed at 2.5 mg/kg b.w. (mice, i.p.), and the effect was stronger than that observed for imipramine (5 mg/kg b.w.). Sedative activity was observed at ED 50 (locomotor test, mice, i.p.) = 17.5 mg/kg b.w. and neurotoxicity was observed at TD 50 (rotarod, mice, i.p.) = 53.2 mg/kg b.w.