{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T18:32:13Z","timestamp":1781893933534,"version":"3.54.5"},"reference-count":91,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Depression is a disease that affects millions of people worldwide, and the discovery and development of effective and safe antidepressant drugs is one of the important topics of psychopharmacology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>In this study, it was aimed to investigate the antidepressant-like activity potential of tofisopam, an anxiolytic drug with 2,3-benzodiazepine structure, and to elucidate the pharmacological mechanisms mediating this effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The antidepressant-like activity of tofisopam was investigated using tail suspension and modified forced swimming tests. Possible interactions of tofisopam with \u00b5- and \u03b4-opioid receptor subtypes were clarified by pharmacological antagonism, molecular docking and molecular dynamics simulation studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Tofisopam (50 and 100\u2009mg\/kg) significantly shortened the immobility time of mice in both the tail suspension and the modified forced swimming tests. The drug, at the same doses, prolonged the duration of swimming and climbing behaviours measured in modified forced swimming tests. A dosage of 25\u2009mg\/kg was ineffective. Mechanistic studies showed that the pretreatment with p-chlorophenylalanine methyl ester (serotonin synthesis inhibitor; 4 consecutive days, 100\u2009mg\/kg), \u03b1-methyl-para-tyrosine methyl ester (catecholamine synthesis inhibitor; 100\u2009mg\/kg), naloxonazine (selective \u00b5-opioid receptor blocker, 7\u2009mg\/kg) and naltrindole (a selective \u03b4-opioid receptor blocker, 0.99\u2009mg\/kg) abolished the anti-immobility effect induced by the 50\u2009mg\/kg dose of tofisopam in the tail suspension tests. Our in silico studies supported the behavioural findings that the antidepressant-like effect of tofisopam is mediated by \u03bc- and \u03b4-opioid receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This study is the first to show that tofisopam has antidepressant-like activity mediated by the serotonergic, catecholaminergic and opioidergic systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811221095528","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T02:46:00Z","timestamp":1653965160000},"page":"819-835","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study"],"prefix":"10.1177","volume":"36","author":[{"given":"Nazl\u0131","family":"Turan Y\u00fccel","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf Evrim","family":"Evren","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski\u015fehir, Turkey"},{"name":"Pharmacy Services, Vocational School of Health Services, Bilecik \u015eeyh Edebali University, Bilecik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmm\u00fchan","family":"Kandemir","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Anadolu University, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-3174","authenticated-orcid":false,"given":"\u00d6zg\u00fcr Devrim","family":"Can","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"bibr1-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(01)00348-8"},{"key":"bibr2-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/srep34984"},{"key":"bibr3-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1177\/0269881115586937"},{"key":"bibr4-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14060"},{"key":"bibr5-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07571.2000"},{"key":"bibr6-02698811221095528","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2015.1025287"},{"key":"bibr7-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.08.036"},{"key":"bibr8-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2021.170547"},{"key":"bibr9-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01093-2"},{"key":"bibr10-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1097\/HRP.0000000000000242"},{"key":"bibr11-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.04.009"},{"key":"bibr12-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.172948"},{"key":"bibr13-02698811221095528","volume":"59","author":"Can A","year":"2012","journal-title":"Journal of Visualized Experiments: Jove"},{"key":"bibr14-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.10.017"},{"key":"bibr15-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.09.023"},{"key":"bibr16-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06827.x"},{"key":"bibr17-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.06.003"},{"key":"bibr18-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax9115"},{"key":"bibr19-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)02017-5"},{"key":"bibr20-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.009"},{"key":"bibr21-02698811221095528","volume":"75","author":"Deacon RM","year":"2013","journal-title":"Journal of Visualized Experiments: Jove"},{"key":"bibr22-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2013.04.014"},{"key":"bibr23-02698811221095528","unstructured":"Desmond Molecular Dynamics System (2020) D. E. Shaw Research. New York, NY, 2021. Schr\u00f6dinger, Maestro-Desmond Interoperability Tools, Schr\u00f6dinger, New York, NY, 2020. https:\/\/www.schrodinger.com\/products\/desmond"},{"key":"bibr24-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1002\/jps.3030460322"},{"key":"bibr25-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-71"},{"key":"bibr26-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3723-y"},{"key":"bibr27-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01056-X"},{"key":"bibr28-02698811221095528","doi-asserted-by":"publisher","DOI":"10.2174\/1568026618666181115095920"},{"key":"bibr29-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-006-9053-3"},{"key":"bibr30-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00645-9"},{"key":"bibr31-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.05.008"},{"key":"bibr32-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"bibr33-02698811221095528","unstructured":"Glide (2020). Schr\u00f6dinger, Schr\u00f6dinger Release 2020-3. New York, NY: Schr\u00f6dinger, LLC. https:\/\/www.schrodinger.com\/products\/glide"},{"key":"bibr34-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2007.07.023"},{"key":"bibr35-02698811221095528","first-page":"109","volume":"2","author":"Hamed A","year":"2007","journal-title":"Farmakoterapia w Psychiatrii i Neurologii"},{"key":"bibr36-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.03.065"},{"key":"bibr37-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00020-9"},{"key":"bibr38-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/nature14886"},{"key":"bibr39-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.10136SC"},{"issue":"9","key":"bibr40-02698811221095528","first-page":"3213","volume":"39","author":"Islam R","year":"2021","journal-title":"Journal of Biomolecular Structure & Dynamics"},{"key":"bibr41-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05649-y"},{"key":"bibr42-02698811221095528","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.642493"},{"key":"bibr43-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1124\/mi.6.3.7"},{"key":"bibr44-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.11.1199"},{"issue":"3","key":"bibr45-02698811221095528","first-page":"499","volume":"154","author":"Koe BK","year":"1966","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"bibr46-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2009.11.015"},{"key":"bibr47-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.66"},{"key":"bibr48-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32833befe5"},{"key":"bibr49-02698811221095528","unstructured":"LigPrep (2020). Schr\u00f6dinger, Schr\u00f6dinger Release 2020-3. New York, NY: Schr\u00f6dinger, LLC. https:\/\/www.schrodinger.com\/products\/ligprep"},{"key":"bibr50-02698811221095528","unstructured":"Maestro (2020). Schr\u00f6dinger, Schr\u00f6dinger Release 2020-3. New York, NY: Schr\u00f6dinger, LLC. https:\/\/www.schrodinger.com\/products\/maestro"},{"key":"bibr51-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6699028"},{"issue":"3","key":"bibr52-02698811221095528","first-page":"1101","volume":"298","author":"Mayorga AJ","year":"2001","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"bibr53-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2018.07.003"},{"key":"bibr54-02698811221095528","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.65.202"},{"key":"bibr55-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.07.091"},{"key":"bibr56-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.19139"},{"key":"bibr57-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.64.179"},{"key":"bibr58-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.06.022"},{"key":"bibr59-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15596"},{"key":"bibr60-02698811221095528","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2019.23.6.427"},{"key":"bibr61-02698811221095528","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7176.101776"},{"key":"bibr62-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/0149-7634(86)90026-6"},{"key":"bibr63-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2020.1781812"},{"issue":"2","key":"bibr64-02698811221095528","first-page":"79","volume":"63","author":"Pet\u00f3cz L","year":"1993","journal-title":"Acta Pharmaceutica Hungarica"},{"key":"bibr65-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.4.2458"},{"key":"bibr66-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.09.009"},{"key":"bibr67-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050638"},{"key":"bibr68-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.10.050"},{"key":"bibr69-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0507-3"},{"key":"bibr70-02698811221095528","doi-asserted-by":"publisher","DOI":"10.2174\/157015912803217314"},{"key":"bibr71-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.60"},{"key":"bibr72-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1039\/C8TX00105G"},{"key":"bibr73-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(00)00233-3"},{"key":"bibr74-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000641"},{"key":"bibr75-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.044"},{"key":"bibr76-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb04963.x"},{"key":"bibr77-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.6.2046"},{"key":"bibr78-02698811221095528","first-page":"1","volume":"17","author":"Srivastava S","year":"2014","journal-title":"Delhi Pschiatry Journal"},{"key":"bibr79-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/BF00428203"},{"key":"bibr80-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2018.04.077"},{"issue":"2","key":"bibr81-02698811221095528","first-page":"91","volume":"63","author":"Szeg\u00f3 J","year":"1993","journal-title":"Acta Pharmaceutica Hungarica"},{"key":"bibr82-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddstr.2004.08.018"},{"key":"bibr83-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.037861"},{"key":"bibr84-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.04.076"},{"key":"bibr85-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.03.020"},{"key":"bibr86-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-021-00821-0"},{"key":"bibr87-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2020.172858"},{"key":"bibr88-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.24.15541"},{"key":"bibr89-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1007\/BF00495547"},{"key":"bibr90-02698811221095528","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18020138"},{"issue":"1","key":"bibr91-02698811221095528","first-page":"12","volume":"11","author":"Y\u0131lmaz B","year":"2006","journal-title":"F\u0131rat Medical Journal"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811221095528","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02698811221095528","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811221095528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:11:02Z","timestamp":1777507862000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02698811221095528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,30]]},"references-count":91,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1177\/02698811221095528"],"URL":"https:\/\/doi.org\/10.1177\/02698811221095528","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,30]]}}}