Wei-Li Lee, Xavier Westergaard, Christopher Hwu, Jennifer Hwu, Tomas Fiala, Clay Lacefield, Umed Boltaev, Adriana M Mendieta, Lisa Lin, Mark S Sonders, Keaon R Brown, Keer He, Wesley B Asher, Jonathan A Javitch, David Sulzer, Dalibor Sames
The serotonergic transmitter system plays fundamental roles in the nervous system in neurotransmission, synaptic plasticity, pathological processes, and therapeutic effects of antidepressants and psychedelics, as well as in the gastrointestinal and circulatory systems. We introduce a novel small molecule fluorescent agent, termed SERTlight , that specifically labels serotonergic neuronal cell bodies, dendrites, and axonal projections as a serotonin transporter (SERT) fluorescent substrate. SERTlight was developed by an iterative molecular design process, based on an aminoethyl-quinolone system, to integrate structural elements that impart SERT substrate activity, sufficient fluorescent brightness, and a broad absence of pharmacological activity, including at serotonin (5-hydroxytryptamine, 5HT) receptors, other G protein-coupled receptors (GPCRs), ion channels, and monoamine transporters...
April 1, 2024: Journal of the American Chemical Society