{"created":"2023-05-15T14:36:39.633578+00:00","id":47224,"links":{},"metadata":{"_buckets":{"deposit":"85e07fe2-71f4-42e1-8394-b301fece9398"},"_deposit":{"created_by":1,"id":"47224","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"47224"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00047224","sets":["1"]},"author_link":["472154","472157","472148","472158","472151","472159","472150","472152","472153","472155","472156","472149"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2012-08","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"8","bibliographicPageStart":"e42589","bibliographicVolumeNumber":"7","bibliographic_titles":[{"bibliographic_title":"PLoS ONE (Online only:URL:http://www.plosone.org)"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT1A) receptor, called Wf-516 (structural formula:(2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4 oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT1A receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT1A receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT1A receptors. In addition, [35S]guanosine 5'-O-[-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT1A receptors. This finding has\nlent support to reports that diverse partial agonists for 5-HT1A receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.","subitem_description_type":"Abstract"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"22880045","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1371/journal.pone.0042589","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1932-6203","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Saijo, Takeaki"}],"nameIdentifiers":[{"nameIdentifier":"472148","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Maeda, Jun"}],"nameIdentifiers":[{"nameIdentifier":"472149","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suzuki, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"472150","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fukumura, Toshimitsu"}],"nameIdentifiers":[{"nameIdentifier":"472151","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suhara, Tetsuya"}],"nameIdentifiers":[{"nameIdentifier":"472152","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"472153","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"西條 武明","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472154","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"前田 純","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472155","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"鈴木 雅之","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472156","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"福村 利光","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472157","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須原 哲也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472158","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"樋口 真人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"472159","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Presynaptic Selectivity of a Ligand for Serotonin 1A Receptors Revealed by In Vivo PET Assays of Rat Brain","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Presynaptic Selectivity of a Ligand for Serotonin 1A Receptors Revealed by In Vivo PET Assays of Rat Brain"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-08-06"},"publish_date":"2015-08-06","publish_status":"0","recid":"47224","relation_version_is_last":true,"title":["Presynaptic Selectivity of a Ligand for Serotonin 1A Receptors Revealed by In Vivo PET Assays of Rat Brain"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:42:24.631452+00:00"}