title: Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT₇ Receptor: Synthesis, Pharmacology, Radiolabeling, and in Vivo Brain Imaging in Pigs.
abstract: We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970.
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.|‡Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Herth
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.|‡Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Valdemar L
authors.initials: VL
authors.lastname: Andersen
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Hanne D
authors.initials: HD
authors.lastname: Hansen
authors.affiliation: §Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institute and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Stroth
authors.affiliation: ∥Egis Pharmaceuticals Plc, P.O. Box 100, H-1475 Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Volk
authors.affiliation: ⊥PET and Cyclotron Unit, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Lehel
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Dyssegaard
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Ettrup
authors.affiliation: §Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institute and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: †Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.|‡Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Jesper L
authors.initials: JL
authors.lastname: Kristensen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D000078183:Oxindoles; D010636:Phenols / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011985:Receptors, Serotonin / Q000032:analysis* / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D013552:Swine
chemical_list: D002250:Carbon Radioisotopes; D007211:Indoles; D008024:Ligands; D000078183:Oxindoles; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D013449:Sulfonamides; C104425:serotonin 7 receptor; C022960:2-oxindole