Synthesis and Evaluation of Antidepressant-like Activity of Some 4-Substituted 1-(2-methoxyphenyl)Piperazine Derivatives
Anna M. Waszkielewicz, Karolina Pytka, Anna Rapacz, Elżbieta Wełna, Monika Jarzyna, Grzegorz Satała, Andrzej Bojarski, Jacek Sapa, Paweł Żmudzki, Barbara Filipek and Henryk Marona
Article first published online: 14 AUG 2014 | DOI: 10.1111/cbdd.12394
New N-(2-methoxyphenyl)piperazine derivatives have been synthesized for their affinity towards serotonergic receptors and for their potential antidepressant-like activity(tail suspension, locomotor activity, and motor coordination tests). All the tested compounds proved very good affinities towards 5-HT1A and 5-HT7. The most promising was 1-[(2-chlor-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazinehydrochloride, exhibiting Ki <1 nM (5-HT1A), and Ki = 34 nM (5-HT7), activity in tail suspension test at 2.5 mg/kg b.w. (mice, i.p.);sedative activity ED50 (locomotor test, mice, i.p.) = 17.5 mg/kg b.w. and neurotoxicity TD50 (rotarod, mice, i.p.) = 53.2 mg/kg b.w.