Synthesis and Evaluation of Antidepressant‐like Activity of Some 4‐Substituted 1‐(2‐methoxyphenyl)Piperazine Derivatives. (14th August 2014)

• Record Type: Journal Article
• Authors: Waszkielewicz, Anna M.; Pytka, Karolina; Rapacz, Anna; Wełna, Elżbieta; Jarzyna, Monika; Satała, Grzegorz; Bojarski, Andrzej; Sapa, Jacek; Żmudzki, Paweł; Filipek, Barbara; Marona, Henryk
• Is Part Of: Chemical biology & drug design. Volume 85:Number 3(2015:Mar.)
• Page Start: 326
• Page End: 335
• Publication Date: 2014-08-14
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12394
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12394-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of new derivatives of <italic>N</italic>‐(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‐HT₆, and 5‐HT₇, as well as <italic>in vivo</italic> 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‐HT₇ receptors. The most promising compound was 1‐[(2‐chloro‐6‐methylphenoxy)ethoxyethyl]‐4‐(2‐methoxyphenyl)piperazine hydrochloride, exhibiting affinity toward receptors <italic>K</italic>_i &lt;1 n<sc>m</sc> (5‐HT_1A) and <italic>K</italic>_i = 34 n<sc>m</sc> (5‐HT₇). 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 ED₅₀ (locomotor test, mice, i.p.) = 17.5 mg/kg b.w. and neurotoxicity was observed at TD₅₀ (rotarod, mice, i.p.) = 53.2 mg/kg b.w.</p> </abstract>