A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter

作者：Zhang, Peng; Jorgensen, Trine Nygaard; Loland, Claus J.; Newman, Amy Hauck^*

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(1): 323-326.

DOI：10.1016/j.bmcl.2012.10.089

• Fluorescent ligand
• Citalopram
• SERT
• Rhodamine

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 [H-3]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. Published by Elsevier Ltd.

• 出版日期2013-1-1