title: Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors.
abstract: A series of arylalkanol-piperidine derivatives was synthesized, and their triple reuptake inhibition and in vivo activities have been evaluated. Among them, compounds 2a, 2j, 2k, 2m and 2n exhibited high potency for 5-HT, NA and DA transporters. Optimized compounds 2j and 2m showed significant reduction of immobility time compared to that of vehicle in the mouse tail suspension test (TST) test at doses ranging from 10 to 50 mg/kg po, and were not generally motor stimulants at 50 mg/kg dose. In addition, compounds 2j and 2m displayed desirable pharmacokinetic properties in SD rats.
authors.affiliation: Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No.1 Road, Shanghai 200437, PR China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Xue-Chu
authors.initials: XC
authors.lastname: Zhen
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Li
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D008297:Male; D051379:Mice; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017982:Receptors, Biogenic Amine / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors; D010880:Piperidines; D017982:Receptors, Biogenic Amine