Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain
Vortioxetine is a multimodal antidepressant approved for treatment of major depressive disorder. Preclinical studies have demonstrated that the mechanism of action of vortioxetine might be different from selective serotonin reuptake inhibitors (SSRIs), including larger serotonin (5-HT) release and d...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2019-09, Vol.44 (10), p.1706-1713 |
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| creator | Yang, Kai-Chun Stepanov, Vladimir Amini, Nahid Martinsson, Stefan Takano, Akihiro Bundgaard, Christoffer Bang-Andersen, Benny Sanchez, Connie Halldin, Christer Farde, Lars Finnema, Sjoerd J |
| description | Vortioxetine is a multimodal antidepressant approved for treatment of major depressive disorder. Preclinical studies have demonstrated that the mechanism of action of vortioxetine might be different from selective serotonin reuptake inhibitors (SSRIs), including larger serotonin (5-HT) release and direct modulation of several 5-HT receptors. In the current positron emission tomography (PET) study, we evaluated the mechanism of action of vortioxetine by comparing its effect to the SSRI citalopram on the binding of [
C]AZ10419369 to the 5-HT
receptor in the nonhuman primate brain. Initially, the 5-HT transporter (5-HTT) binding of vortioxetine was determined by [
C]MADAM PET measurements before and after administration of vortioxetine (0.1-3.0 mg/kg) and data were used to confirm clinically relevant dosing in subsequent PET measurements with [
C]AZ10419369. The 5-HT
receptor binding was significantly decreased after 0.3 mg/kg of citalopram in the dorsal raphe nucleus (5%), as well as after 0.3 mg/kg of vortioxetine in six brain regions (~25%) or 1.0 mg/kg of vortioxetine in all 12 examined regions (~48%). Moreover, there was no effect of 1.0 mg/kg of vortioxetine on the binding of [
C]Cimbi-36 to the 5-HT
receptor, which has comparable sensitivity to 5-HT release as [
C]AZ10419369 binding. In conclusion, at clinically relevant doses, vortioxetine induced larger reductions in [
C]AZ10419369 binding than citalopram. These observations suggest that vortioxetine binds to the 5-HT
receptor at clinically relevant doses. Future studies are warranted to evaluate the role of the 5-HT
receptor in the therapeutic effects of vortioxetine and as a potential target for the development of novel antidepressant drugs. |
| doi_str_mv | 10.1038/s41386-019-0442-4 |
| format | Article |
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C]AZ10419369 to the 5-HT
receptor in the nonhuman primate brain. Initially, the 5-HT transporter (5-HTT) binding of vortioxetine was determined by [
C]MADAM PET measurements before and after administration of vortioxetine (0.1-3.0 mg/kg) and data were used to confirm clinically relevant dosing in subsequent PET measurements with [
C]AZ10419369. The 5-HT
receptor binding was significantly decreased after 0.3 mg/kg of citalopram in the dorsal raphe nucleus (5%), as well as after 0.3 mg/kg of vortioxetine in six brain regions (~25%) or 1.0 mg/kg of vortioxetine in all 12 examined regions (~48%). Moreover, there was no effect of 1.0 mg/kg of vortioxetine on the binding of [
C]Cimbi-36 to the 5-HT
receptor, which has comparable sensitivity to 5-HT release as [
C]AZ10419369 binding. In conclusion, at clinically relevant doses, vortioxetine induced larger reductions in [
C]AZ10419369 binding than citalopram. These observations suggest that vortioxetine binds to the 5-HT
receptor at clinically relevant doses. Future studies are warranted to evaluate the role of the 5-HT
receptor in the therapeutic effects of vortioxetine and as a potential target for the development of novel antidepressant drugs.</description><identifier>ISSN: 0893-133X</identifier><identifier>ISSN: 1740-634X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/s41386-019-0442-4</identifier><identifier>PMID: 31216565</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Animals ; Antidepressants ; Benzopyrans ; Benzylamines ; Brain ; Brain - diagnostic imaging ; Brain - drug effects ; Brain - metabolism ; Citalopram ; Citalopram - metabolism ; Citalopram - pharmacology ; Dorsal raphe nucleus ; Dorsal Raphe Nucleus - diagnostic imaging ; Dorsal Raphe Nucleus - drug effects ; Dorsal Raphe Nucleus - metabolism ; Dosage ; Drug development ; Emission analysis ; Female ; Macaca mulatta ; Medicin och hälsovetenskap ; Morpholines ; Phenethylamines ; Piperazines ; Positron emission tomography ; Raphe nuclei ; Receptor, Serotonin, 5-HT1B - metabolism ; Receptor, Serotonin, 5-HT2A - metabolism ; Serotonin ; Serotonin S1 receptors ; Serotonin S2 receptors ; Serotonin uptake inhibitors ; Serotonin Uptake Inhibitors - metabolism ; Serotonin Uptake Inhibitors - pharmacology ; Vortioxetine - metabolism ; Vortioxetine - pharmacology</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2019-09, Vol.44 (10), p.1706-1713</ispartof><rights>Copyright Nature Publishing Group Sep 2019</rights><rights>American College of Neuropsychopharmacology 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-b99736376e56fb09e1da4a13f3e186cceec06d9244a81b624980da9ab4e4cb5f3</citedby><cites>FETCH-LOGICAL-c515t-b99736376e56fb09e1da4a13f3e186cceec06d9244a81b624980da9ab4e4cb5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784989/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784989/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,553,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31216565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:141633895$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Kai-Chun</creatorcontrib><creatorcontrib>Stepanov, Vladimir</creatorcontrib><creatorcontrib>Amini, Nahid</creatorcontrib><creatorcontrib>Martinsson, Stefan</creatorcontrib><creatorcontrib>Takano, Akihiro</creatorcontrib><creatorcontrib>Bundgaard, Christoffer</creatorcontrib><creatorcontrib>Bang-Andersen, Benny</creatorcontrib><creatorcontrib>Sanchez, Connie</creatorcontrib><creatorcontrib>Halldin, Christer</creatorcontrib><creatorcontrib>Farde, Lars</creatorcontrib><creatorcontrib>Finnema, Sjoerd J</creatorcontrib><title>Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Vortioxetine is a multimodal antidepressant approved for treatment of major depressive disorder. Preclinical studies have demonstrated that the mechanism of action of vortioxetine might be different from selective serotonin reuptake inhibitors (SSRIs), including larger serotonin (5-HT) release and direct modulation of several 5-HT receptors. In the current positron emission tomography (PET) study, we evaluated the mechanism of action of vortioxetine by comparing its effect to the SSRI citalopram on the binding of [
C]AZ10419369 to the 5-HT
receptor in the nonhuman primate brain. Initially, the 5-HT transporter (5-HTT) binding of vortioxetine was determined by [
C]MADAM PET measurements before and after administration of vortioxetine (0.1-3.0 mg/kg) and data were used to confirm clinically relevant dosing in subsequent PET measurements with [
C]AZ10419369. The 5-HT
receptor binding was significantly decreased after 0.3 mg/kg of citalopram in the dorsal raphe nucleus (5%), as well as after 0.3 mg/kg of vortioxetine in six brain regions (~25%) or 1.0 mg/kg of vortioxetine in all 12 examined regions (~48%). Moreover, there was no effect of 1.0 mg/kg of vortioxetine on the binding of [
C]Cimbi-36 to the 5-HT
receptor, which has comparable sensitivity to 5-HT release as [
C]AZ10419369 binding. In conclusion, at clinically relevant doses, vortioxetine induced larger reductions in [
C]AZ10419369 binding than citalopram. These observations suggest that vortioxetine binds to the 5-HT
receptor at clinically relevant doses. Future studies are warranted to evaluate the role of the 5-HT
receptor in the therapeutic effects of vortioxetine and as a potential target for the development of novel antidepressant drugs.</description><subject>Animals</subject><subject>Antidepressants</subject><subject>Benzopyrans</subject><subject>Benzylamines</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Citalopram</subject><subject>Citalopram - metabolism</subject><subject>Citalopram - pharmacology</subject><subject>Dorsal raphe nucleus</subject><subject>Dorsal Raphe Nucleus - diagnostic imaging</subject><subject>Dorsal Raphe Nucleus - drug effects</subject><subject>Dorsal Raphe Nucleus - metabolism</subject><subject>Dosage</subject><subject>Drug development</subject><subject>Emission analysis</subject><subject>Female</subject><subject>Macaca mulatta</subject><subject>Medicin och hälsovetenskap</subject><subject>Morpholines</subject><subject>Phenethylamines</subject><subject>Piperazines</subject><subject>Positron emission tomography</subject><subject>Raphe nuclei</subject><subject>Receptor, Serotonin, 5-HT1B - metabolism</subject><subject>Receptor, Serotonin, 5-HT2A - metabolism</subject><subject>Serotonin</subject><subject>Serotonin S1 receptors</subject><subject>Serotonin S2 receptors</subject><subject>Serotonin uptake inhibitors</subject><subject>Serotonin Uptake Inhibitors - metabolism</subject><subject>Serotonin Uptake Inhibitors - pharmacology</subject><subject>Vortioxetine - metabolism</subject><subject>Vortioxetine - pharmacology</subject><issn>0893-133X</issn><issn>1740-634X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNp1kk9v1DAQxS0EosvCB-CCLHHhErBjx7EvSKha_kiV4FCk3izHmXTdJvZiOwuV-PA47LZQJE62PL_3ZsZ6CD2n5DUlTL5JnDIpKkJVRTivK_4ArWjLSSUYv3iIVkQqVlHGLk7Qk5SuCKFNK-RjdMJoTUUjmhX6uRkGsBmHAdvReWfNON7gCCPsjc-4DwnSUtyHmF34Adl5wMb32LpsxrCLZsLB4wQx5OAhXjqLv2zO8WTiNcSEncd5C9gHv50n4_EuuslkwF00zj9FjwYzJnh2PNfo6_vN-enH6uzzh0-n784q29AmV51SLROsFdCIoSMKaG-4oWxgQKWwFsAS0auacyNpJ2quJOmNMh0HbrtmYGtUHXzTd9jNnf49RLzRwTh9fLouN9C8lUqowqv_8rsY-j-iWyHlVDAmVVO0bw_aAkzQW_A5mvG-xb2Kd1t9GfZatLIMvjR_dTSI4dsMKevJJQvjaDyEOem67EkZkZIX9OU_6FWYoy9fWai2bqla0DWiB8rGkFKE4W4YSvSSI33IkS450kuO9OL84u8t7hS3wWG_ACifyDI</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Yang, Kai-Chun</creator><creator>Stepanov, Vladimir</creator><creator>Amini, Nahid</creator><creator>Martinsson, Stefan</creator><creator>Takano, Akihiro</creator><creator>Bundgaard, Christoffer</creator><creator>Bang-Andersen, Benny</creator><creator>Sanchez, Connie</creator><creator>Halldin, Christer</creator><creator>Farde, Lars</creator><creator>Finnema, Sjoerd J</creator><general>Nature Publishing Group</general><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20190901</creationdate><title>Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain</title><author>Yang, Kai-Chun ; Stepanov, Vladimir ; Amini, Nahid ; Martinsson, Stefan ; Takano, Akihiro ; Bundgaard, Christoffer ; Bang-Andersen, Benny ; Sanchez, Connie ; Halldin, Christer ; Farde, Lars ; Finnema, Sjoerd J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-b99736376e56fb09e1da4a13f3e186cceec06d9244a81b624980da9ab4e4cb5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antidepressants</topic><topic>Benzopyrans</topic><topic>Benzylamines</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Citalopram</topic><topic>Citalopram - metabolism</topic><topic>Citalopram - pharmacology</topic><topic>Dorsal raphe nucleus</topic><topic>Dorsal Raphe Nucleus - diagnostic imaging</topic><topic>Dorsal Raphe Nucleus - drug effects</topic><topic>Dorsal Raphe Nucleus - metabolism</topic><topic>Dosage</topic><topic>Drug development</topic><topic>Emission analysis</topic><topic>Female</topic><topic>Macaca mulatta</topic><topic>Medicin och hälsovetenskap</topic><topic>Morpholines</topic><topic>Phenethylamines</topic><topic>Piperazines</topic><topic>Positron emission tomography</topic><topic>Raphe nuclei</topic><topic>Receptor, Serotonin, 5-HT1B - metabolism</topic><topic>Receptor, Serotonin, 5-HT2A - metabolism</topic><topic>Serotonin</topic><topic>Serotonin S1 receptors</topic><topic>Serotonin S2 receptors</topic><topic>Serotonin uptake inhibitors</topic><topic>Serotonin Uptake Inhibitors - metabolism</topic><topic>Serotonin Uptake Inhibitors - pharmacology</topic><topic>Vortioxetine - metabolism</topic><topic>Vortioxetine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Kai-Chun</creatorcontrib><creatorcontrib>Stepanov, Vladimir</creatorcontrib><creatorcontrib>Amini, Nahid</creatorcontrib><creatorcontrib>Martinsson, Stefan</creatorcontrib><creatorcontrib>Takano, Akihiro</creatorcontrib><creatorcontrib>Bundgaard, Christoffer</creatorcontrib><creatorcontrib>Bang-Andersen, Benny</creatorcontrib><creatorcontrib>Sanchez, Connie</creatorcontrib><creatorcontrib>Halldin, Christer</creatorcontrib><creatorcontrib>Farde, Lars</creatorcontrib><creatorcontrib>Finnema, Sjoerd J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Kai-Chun</au><au>Stepanov, Vladimir</au><au>Amini, Nahid</au><au>Martinsson, Stefan</au><au>Takano, Akihiro</au><au>Bundgaard, Christoffer</au><au>Bang-Andersen, Benny</au><au>Sanchez, Connie</au><au>Halldin, Christer</au><au>Farde, Lars</au><au>Finnema, Sjoerd J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain</atitle><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle><addtitle>Neuropsychopharmacology</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>44</volume><issue>10</issue><spage>1706</spage><epage>1713</epage><pages>1706-1713</pages><issn>0893-133X</issn><issn>1740-634X</issn><eissn>1740-634X</eissn><abstract>Vortioxetine is a multimodal antidepressant approved for treatment of major depressive disorder. Preclinical studies have demonstrated that the mechanism of action of vortioxetine might be different from selective serotonin reuptake inhibitors (SSRIs), including larger serotonin (5-HT) release and direct modulation of several 5-HT receptors. In the current positron emission tomography (PET) study, we evaluated the mechanism of action of vortioxetine by comparing its effect to the SSRI citalopram on the binding of [
C]AZ10419369 to the 5-HT
receptor in the nonhuman primate brain. Initially, the 5-HT transporter (5-HTT) binding of vortioxetine was determined by [
C]MADAM PET measurements before and after administration of vortioxetine (0.1-3.0 mg/kg) and data were used to confirm clinically relevant dosing in subsequent PET measurements with [
C]AZ10419369. The 5-HT
receptor binding was significantly decreased after 0.3 mg/kg of citalopram in the dorsal raphe nucleus (5%), as well as after 0.3 mg/kg of vortioxetine in six brain regions (~25%) or 1.0 mg/kg of vortioxetine in all 12 examined regions (~48%). Moreover, there was no effect of 1.0 mg/kg of vortioxetine on the binding of [
C]Cimbi-36 to the 5-HT
receptor, which has comparable sensitivity to 5-HT release as [
C]AZ10419369 binding. In conclusion, at clinically relevant doses, vortioxetine induced larger reductions in [
C]AZ10419369 binding than citalopram. These observations suggest that vortioxetine binds to the 5-HT
receptor at clinically relevant doses. Future studies are warranted to evaluate the role of the 5-HT
receptor in the therapeutic effects of vortioxetine and as a potential target for the development of novel antidepressant drugs.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>31216565</pmid><doi>10.1038/s41386-019-0442-4</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0893-133X |
| ispartof | Neuropsychopharmacology (New York, N.Y.), 2019-09, Vol.44 (10), p.1706-1713 |
| issn | 0893-133X 1740-634X 1740-634X |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_478969 |
| source | MEDLINE; SWEPUB Freely available online; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Antidepressants Benzopyrans Benzylamines Brain Brain - diagnostic imaging Brain - drug effects Brain - metabolism Citalopram Citalopram - metabolism Citalopram - pharmacology Dorsal raphe nucleus Dorsal Raphe Nucleus - diagnostic imaging Dorsal Raphe Nucleus - drug effects Dorsal Raphe Nucleus - metabolism Dosage Drug development Emission analysis Female Macaca mulatta Medicin och hälsovetenskap Morpholines Phenethylamines Piperazines Positron emission tomography Raphe nuclei Receptor, Serotonin, 5-HT1B - metabolism Receptor, Serotonin, 5-HT2A - metabolism Serotonin Serotonin S1 receptors Serotonin S2 receptors Serotonin uptake inhibitors Serotonin Uptake Inhibitors - metabolism Serotonin Uptake Inhibitors - pharmacology Vortioxetine - metabolism Vortioxetine - pharmacology |
| title | Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T02%3A55%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20clinically%20relevant%20doses%20of%20vortioxetine%20and%20citalopram%20on%20serotonergic%20PET%20markers%20in%20the%20nonhuman%20primate%20brain&rft.jtitle=Neuropsychopharmacology%20(New%20York,%20N.Y.)&rft.au=Yang,%20Kai-Chun&rft.date=2019-09-01&rft.volume=44&rft.issue=10&rft.spage=1706&rft.epage=1713&rft.pages=1706-1713&rft.issn=0893-133X&rft.eissn=1740-634X&rft_id=info:doi/10.1038/s41386-019-0442-4&rft_dat=%3Cproquest_swepu%3E2272719441%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2272719441&rft_id=info:pmid/31216565&rfr_iscdi=true |