Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors

Eur J Med Chem. 2012 Aug:54:123-36. doi: 10.1016/j.ejmech.2012.04.030. Epub 2012 Apr 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / chemistry*
  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacokinetics
  • Antidepressive Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Male
  • Mice
  • Neurotransmitter Uptake Inhibitors / chemistry*
  • Neurotransmitter Uptake Inhibitors / metabolism
  • Neurotransmitter Uptake Inhibitors / pharmacokinetics
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Piperidines / chemistry*
  • Piperidines / metabolism
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Biogenic Amine / metabolism

Substances

  • Antidepressive Agents
  • Neurotransmitter Uptake Inhibitors
  • Piperidines
  • Receptors, Biogenic Amine