title: Antidepressant-like Effects of LPM580153, A Novel Potent Triple 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 of depression to assess the antidepressant-like activity of LPM580153, followed by a neurotransmitter uptake assay and a corticosterone-induced cell injury model to explore its mechanism of action. In mice, LPM580153 reduced immobility time in the tail suspension test, and in rats subjected to chronic unpredictable mild stress it reversed reductions in body weight gain and ameliorated anhedonia. The neurotransmitter uptake assay results demonstrated that LPM580153 inhibited the uptake of serotonin, norepinephrine and dopamine. Furthermore, LPM580153 protected the SH-SY5Y cells against the cytotoxic activity of corticosterone, an action that might be related to the role of LPM580153 in increasing the protein levels of BDNF, p-ERK1/2, p-AKT, p-CREB and p-mTOR. Together, these findings indicate that LPM580153 is a novel triple reuptake inhibitor with robust antidepressant-like effects.
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.
authors.forename: Fangxi
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The third hospital of Jinan, Jinan, 250132, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: 5Institute of Toxicology, Binzhou Medical University, Yantai, Shandong, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.
authors.forename: Qiaofeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
mesh_terms: D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D003511:Cyclohexanols / Q000737:chemistry / Q000494:pharmacology*; D003863:Depression / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000493:pharmacokinetics; D010627:Phenethylamines / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: C000614914:4-(2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl)phenyl 3-nitrophenyl ether; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D003511:Cyclohexanols; D014179:Neurotransmitter Uptake Inhibitors; D010627:Phenethylamines; D012701:Serotonin; D048049:Extracellular Signal-Regulated MAP Kinases; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine