A series of aralkyl diamine derivatives were designed, synthesized, and evaluated for their triple reuptake inhibitory abilities. Compounds 18c (5-HT, NE, DA, IC50 = 389, 69, 238 nM), 36a (5-HT, NE, DA, IC50 = 378, 477, 247 nM), and 36d (5-HT, NE, DA, IC50 = 501, 206, 357 nM) showed in vivo activities in the rat forced swim test at 5, 10, and 20 mg/kg PO. 36a was identified as the most promising candidate in this study.
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