A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter |
| |
| Authors: | Peng Zhang Trine Nygaard Jørgensen Claus J. Loland Amy Hauck Newman |
| |
| Affiliation: | 1. 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;2. Molecular Neuropharmacology Laboratory and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark |
| |
| 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 [3H]5-HT uptake in COS-7 cells (Ki = 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
