title: Synthesis and evaluation of antidepressant-like activity of some 4-substituted 1-(2-methoxyphenyl)piperazine derivatives.
abstract: 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-HT1A , 5-HT6 , and 5-HT7 , 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-HT1A and 5-HT7 receptors. The most promising compound was 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride, exhibiting affinity toward receptors Ki <1 nm (5-HT1A ) and Ki = 34 nm (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.
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.forename: Karolina
authors.initials: K
authors.lastname: Pytka
authors.forename: Anna
authors.initials: A
authors.lastname: Rapacz
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wełna
authors.forename: Monika
authors.initials: M
authors.lastname: Jarzyna
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Satała
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bojarski
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.forename: Paweł
authors.initials: P
authors.lastname: Żmudzki
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; C040083:1-(2-methoxyphenyl)piperazine
keywords: (2-methoxyphenyl)piperazine; 5-HT; antidepressant-like activity; chimney test; locomotor test; neurotoxicity; rotarod; tail suspension test