Open AccessIlluminating the norepinephrine transporter: fluorescent probes based on nisoxetine and talopram
Author(s) -
Gisela Andrea CamachoHernandez,
Andrea Casiraghi,
Deborah Rudin,
Dino Luethi,
Therese Ku,
Daryl A. Guthrie,
Valentina Straniero,
Ermanno Valoti,
Gerhard J. Schütz,
Harald H. Sitte,
Amy Hauck Newman
Publication year - 2021
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d1md00072a
Subject(s) - norepinephrine transporter , norepinephrine , chemistry , fluorescence , neuroscience , biology , physics , dopamine , optics
The utilization of fluorescent ligands to study the monoamine transporters (MATs) has increased our knowledge of their function and distribution in live cell systems. In this study, we extend SAR for nisoxetine and talopram as parent compounds, to identify high affinity rhodamine-labeled fluorescent probes for the norepinephrine transporter (NET). Nisoxetine-based fluorescent probe 6 demonstrated high binding affinity ( K i = 43 nM) for NET and an overall selectivity compared to the other transporters for dopamine (DAT; K i = 1540 nM) and serotonin (SERT; K i = 785 nM) in competitive radioligand binding assays. Using confocal microscopy, compound 6 was shown to stain both NET and SERT, but not DAT, at low nanomolar concentrations, in transporter-expressing cells.