title: A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter.
abstract: A novel fluorescent ligand was synthesized as a high-affinity, high specificity probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore was extended from an aniline substitution on the 5-position of the dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), using an ethylamino linker. The resulting rhodamine-labeled ligand 8 inhibited [(3)H]5-HT uptake in COS-7 cells (K(i)=225 nM) with similar potency to the tropane-based JHC 1-064 (1), but with higher specificity towards the SERT relative to the transporters for dopamine and norepinephrine. Visualization of the SERT with compound 8 was demonstrated by confocal microscopy in HEK293 cells stably expressing EGFP-SERT.
authors.affiliation: Molecular Targets and Medications Discovery Branch, Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Trine Nygaard
authors.initials: TN
authors.lastname: Jørgensen
authors.forename: Claus J
authors.initials: CJ
authors.lastname: Loland
authors.forename: Amy Hauck
authors.initials: AH
authors.lastname: Newman
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015283:Citalopram / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D014176:Protein Biosynthesis / Q000187:drug effects; D012235:Rhodamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D012235:Rhodamines; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D049452:Green Fluorescent Proteins