This study describes the chemical synthesis and pharmacological evaluation of some new 1-aryl-3-[(4-benzyl)piperidine-1-yl]propane derivatives as antidepressants. The structures attributed to the compounds were elucidated using IR and 1H-NMR spectroscopic techniques besides elemental analysis. The antidepressant-like effect of these compounds was assessed by using the forced swimming test (FST), a validated experimental model of depression in mice. A clear antidepressant-like effect was shown for compounds 1, 2 and 4 by a significant decrease in immobility behaviour.