Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor

• DOI: 10.1038/srep24233
• Publication Date: 2016-04-07T09:29:44Z
• Authors: Fangxi Zhang; Jing Shao; Jingwei Tian; Yan Zhong; Liang Ye; Xiangjing Meng; Qiaofeng Liu; Hongbo Wang
• Keywords: Serotonin reuptake inhibitor

Abstract The purpose of this study was to characterize a novel compound, 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl) ethyl] phenyl 3-nitrophenyl ether, designated LPM580153. We used several well-validated animal models depression assess the antidepressant-like activity LPM580153, followed by neurotransmitter uptake assay and corticosterone-induced cell injury model explore its mechanism action. In mice, LPM580153 reduced immobility time in tail suspension test, rats subjected chronic unpredictable mild stress it reversed reductions body weight gain ameliorated anhedonia. results demonstrated that inhibited serotonin, norepinephrine dopamine. Furthermore, protected SH-SY5Y cells against cytotoxic corticosterone, an action might be related role increasing protein levels BDNF, p-ERK1/2, p-AKT, p-CREB p-mTOR. Together, these findings indicate is triple reuptake inhibitor with robust effects.