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However, delayed therapeutic onset and undesirable side effects are major drawbacks for conventional serotonin reuptake inhibitors. Here, we show that<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053, a novel serotonin reuptake inhibitor with 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub>partial agonistic activity, displays fast antidepressant efficacy with minimal undesirable effects, especially nausea and emesis in animal models.<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053 bound human serotonin transporter and 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub>receptor with the<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>values of 1.02\u00a0\u00b1\u00a00.06 and 5.05\u00a0\u00b1\u00a01.07\u00a0nmol\/L, respectively. This compound inhibited the serotonin transporter with an<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub>value of 2.74\u00a0\u00b1\u00a00.41\u00a0nmol\/L and had an intrinsic activity for 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub>receptors of 70.0\u00a0\u00b1\u00a06.3%. In rat microdialysis,<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053, given once at 3 and 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>, dose\u2010dependently increased extracellular 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>levels. In the rat forced swimming test, 2\u2010week administration of<jats:styled-content style=\"fixed-case\">DSR<\/jats:styled-content>\u20101053 (1\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) significantly reduced rats immobility time after treatment, whereas paroxetine (3 and 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) required 3\u2010week administration to reduce rats immobility time. In olfactory bulbectomy model, 1\u2010 and 2\u2010week administration of<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053 reduced both of emotional scores and activity in the open field, whereas paroxetine required 2\u00a0weeks to show similar beneficial effects. Although single administration of<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053\u2010induced emesis and vomiting in the rat and<jats:italic>Suncus murinus<\/jats:italic>, multiple treatment with this compound, but not with paroxetine, decreased the number of vomiting episodes. These results highlight the important role of 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub>receptors in both the efficacy and tolerability of<jats:styled-content style=\"fixed-case\">DSP<\/jats:styled-content>\u20101053 as a new therapeutic option for the treatment of depression.<\/jats:p>","DOI":"10.1002\/prp2.142","type":"journal-article","created":{"date-parts":[[2015,6,12]],"date-time":"2015-06-12T12:05:03Z","timestamp":1434110703000},"source":"Crossref","is-referenced-by-count":7,"title":["DSP\u20101053, a novel serotonin reuptake inhibitor with 5\u2010HT<sub>1A<\/sub>partial agonistic activity, displays fast antidepressant effect with minimal undesirable effects in juvenile rats"],"prefix":"10.1002","volume":"3","author":[{"given":"Taro","family":"Kato","sequence":"first","affiliation":[{"name":"Drug Development Research Laboratories Sumitomo Dainippon Pharma Co. Ltd. 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