{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:29:50Z","timestamp":1758709790012},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p>","DOI":"10.1038\/srep24233","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T09:29:44Z","timestamp":1460021384000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor"],"prefix":"10.1038","volume":"6","author":[{"given":"Fangxi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjing","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaofeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"BFsrep24233_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.4088\/JCP.14m09298","volume":"76","author":"PE Greenberg","year":"2015","unstructured":"Greenberg, P. E., Fournier, A. A., Sisitsky, T., Pike, C. T. & Kessler, R. C. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry 76, 155\u2013162 (2015).","journal-title":"J Clin Psychiatry"},{"key":"BFsrep24233_CR2","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1016\/S0140-6736(96)07492-2","volume":"349","author":"CJ Murray","year":"1997","unstructured":"Murray, C. J. & Lopez, A. D. Alternative projections of mortality and disability by cause 1990\u20132020: Global Burden of Disease Study. Lancet 349, 1498\u20131504 (1997).","journal-title":"Lancet"},{"key":"BFsrep24233_CR3","doi-asserted-by":"publisher","first-page":"538","DOI":"10.4065\/mcp.2009.0565","volume":"85","author":"JM Bostwick","year":"2010","unstructured":"Bostwick, J. M. A generalist\u2019s guide to treating patients with depression with an emphasis on using side effects to tailor antidepressant therapy. Mayo Clin Proc 85, 538\u2013550 (2010).","journal-title":"Mayo Clin Proc"},{"key":"BFsrep24233_CR4","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1177\/1060028014550645","volume":"48","author":"NM Jasiak","year":"2014","unstructured":"Jasiak, N. M. & Bostwick, J. R. Risk of QT\/QTc prolongation among newer non-SSRI antidepressants. Ann Pharmacother 48, 1620\u20131628 (2014).","journal-title":"Ann Pharmacother"},{"key":"BFsrep24233_CR5","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1370\/afm.349","volume":"3","author":"B Arroll","year":"2005","unstructured":"Arroll, B. et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med 3, 449\u2013456 (2005).","journal-title":"Ann Fam Med"},{"key":"BFsrep24233_CR6","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1517\/13543784.2014.918951","volume":"23","author":"B Pochwat","year":"2014","unstructured":"Pochwat, B., Palucha-Poniewiera, A., Szewczyk, B., Pilc, A. & Nowak, G. NMDA antagonists under investigation for the treatment of major depressive disorder. Expert Opin Investig Drugs 23, 1181\u20131192 (2014).","journal-title":"Expert Opin Investig Drugs"},{"key":"BFsrep24233_CR7","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.biopsych.2005.09.018","volume":"59","author":"EJ Nestler","year":"2006","unstructured":"Nestler, E. J. & Carlezon, W. A. Jr. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59, 1151\u20131159 (2006).","journal-title":"Biol Psychiatry"},{"key":"BFsrep24233_CR8","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2174\/187152707780363285","volume":"6","author":"P Skolnick","year":"2007","unstructured":"Skolnick, P. & Basile, A. S. Triple reuptake inhibitors (\u201cbroad spectrum\u201d antidepressants). CNS Neurol Disord Drug Targets 6, 141\u2013149 (2007).","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"BFsrep24233_CR9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.4088\/JCP.v63n0302","volume":"63","author":"SH Kennedy","year":"2002","unstructured":"Kennedy, S. H. et al. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry 63, 181\u2013186 (2002).","journal-title":"J Clin Psychiatry"},{"key":"BFsrep24233_CR10","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0014-2999(03)01310-4","volume":"461","author":"P Skolnick","year":"2003","unstructured":"Skolnick, P., Popik, P., Janowsky, A., Beer, B. & Lippa, A. S. Antidepressant-like actions of DOV 21,947: a \u201ctriple\u201d reuptake inhibitor. Eur J Pharmacol 461, 99\u2013104 (2003).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep24233_CR11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ejphar.2006.10.004","volume":"555","author":"AM Shaw","year":"2007","unstructured":"Shaw, A. M. et al. Antidepressant-like effects of novel triple reuptake inhibitors, PRC025 and PRC050. Eur J Pharmacol 555, 30\u201336 (2007).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep24233_CR12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.neuroscience.2011.08.064","volume":"196","author":"JW Tian","year":"2011","unstructured":"Tian, J. W. et al. Preclinical pharmacology of TP1, a novel potent triple reuptake inhibitor with antidepressant properties. Neuroscience 196, 124\u2013130 (2011).","journal-title":"Neuroscience"},{"key":"BFsrep24233_CR13","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.euroneuro.2015.01.005","volume":"25","author":"ZL Jin","year":"2015","unstructured":"Jin, Z. L. et al. The antidepressant-like pharmacological profile of Yuanzhi-1, a novel serotonin, norepinephrine and dopamine reuptake inhibitor. Eur Neuropsychopharmacol 25, 544\u2013556 (2015).","journal-title":"Eur Neuropsychopharmacol"},{"key":"BFsrep24233_CR14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.neubiorev.2005.03.009","volume":"29","author":"JF Cryan","year":"2005","unstructured":"Cryan, J. F., Mombereau, C. & Vassout, A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29, 571\u2013625 (2005).","journal-title":"Neurosci Biobehav Rev"},{"key":"BFsrep24233_CR15","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.pnpbp.2009.01.004","volume":"33","author":"LS Garcia","year":"2009","unstructured":"Garcia, L. S. et al. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 33, 450\u2013455 (2009).","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"BFsrep24233_CR16","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/S0149-7634(05)80194-0","volume":"16","author":"P Willner","year":"1992","unstructured":"Willner, P., Muscat, R. & Papp, M. Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16, 525\u2013534 (1992).","journal-title":"Neurosci Biobehav Rev"},{"key":"BFsrep24233_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00427414","volume":"83","author":"P Willner","year":"1984","unstructured":"Willner, P. The validity of animal models of depression. Psychopharmacology (Berl) 83, 1\u201316 (1984).","journal-title":"Psychopharmacology (Berl)"},{"key":"BFsrep24233_CR18","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s002130050456","volume":"134","author":"P Willner","year":"1997","unstructured":"Willner, P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 134, 319\u2013329 (1997).","journal-title":"Psychopharmacology (Berl)"},{"key":"BFsrep24233_CR19","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tins.2008.06.006","volume":"31","author":"CM Pariante","year":"2008","unstructured":"Pariante, C. M. & Lightman, S. L. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31, 464\u2013468 (2008).","journal-title":"Trends Neurosci"},{"key":"BFsrep24233_CR20","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ejphar.2008.01.014","volume":"583","author":"F Murray","year":"2008","unstructured":"Murray, F., Smith, D. W. & Hutson, P. H. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol 583, 115\u2013127 (2008).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep24233_CR21","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1038\/sj.cdd.4401662","volume":"12","author":"RD Almeida","year":"2005","unstructured":"Almeida, R. D. et al. Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12, 1329\u20131343 (2005).","journal-title":"Cell Death Differ"},{"key":"BFsrep24233_CR22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.pnpbp.2013.04.018","volume":"45","author":"SH Kim","year":"2013","unstructured":"Kim, S. H. et al. Intracerebroventricular administration of ouabain, a Na\/K-ATPase inhibitor, activates mTOR signal pathways and protein translation in the rat frontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 45, 73\u201382 (2013).","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"BFsrep24233_CR23","doi-asserted-by":"publisher","first-page":"5632","DOI":"10.1038\/srep05632","volume":"4","author":"J Tian","year":"2014","unstructured":"Tian, J., Zhang, F., Cheng, J., Guo, S., Liu, P. & Wang, H. Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L. Sci Rep 4, 5632 (2014).","journal-title":"Sci Rep"},{"key":"BFsrep24233_CR24","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/BF02975433","volume":"27","author":"CG Jang","year":"2004","unstructured":"Jang, C. G. et al. Nelumbinis Semen reverses a decrease in 5-HT1A receptor binding induced by chronic mild stress, a depression-like symptom. Arch Pharm Res 27, 1065\u20131072 (2004).","journal-title":"Arch Pharm Res"},{"key":"BFsrep24233_CR25","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/0024-3205(93)90194-8","volume":"52","author":"C Bolden-Watson","year":"1993","unstructured":"Bolden-Watson, C. & Richelson, E. Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 52, 1023\u20131029 (1993).","journal-title":"Life Sci"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep24233.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep24233","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep24233.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:44:05Z","timestamp":1672890245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep24233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,7]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,26]]}},"alternative-id":["BFsrep24233"],"URL":"https:\/\/doi.org\/10.1038\/srep24233","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,7]]},"assertion":[{"value":"4 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24233"}}