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Journal of Biomolecular Screening, Vol. 12, No. 3, 436-441 (2007)
DOI: 10.1177/1087057106297994

High-Throughput Screening for Norepinephrine Transporter Inhibitors Using the FLIPRTetra

Ryan Wagstaff

Department of Pharmacology & Lead Discovery, Neurocrine Bisciences, Inc., San Diego, California

Michael Hedrick

Department of Pharmacology & Lead Discovery, Neurocrine Bisciences, Inc., San Diego, California

Jun Fan

Department of Discovery Biology, Neurocrine Biosciences, Inc., San Diego, California

Paul D. Crowe

Department of Pharmacology & Lead Discovery, Neurocrine Bisciences, Inc., San Diego, California, pcrowe{at}neurocrine.com

Daniel DiSepio

Johnson & Johnson, PRD, San Diego, California, Department of Pharmacology & Lead Discovery, Neurocrine Bisciences, Inc., San Diego, California

Monoamine transporters regulate the concentration of neurotransmitters in the synapse following neurotransmission and are very important drug targets in the pharmaceutical industry. Because of the labor-intensive nature of functional uptake assays using radioactive substrates, high-throughput screening for monoamine transporter inhibitors has been limited to radioligand binding assays. In this article, the authors describe the development of a 384-well, high-throughput functional screening assay for norepinephrine transporter inhibitors using the FLIPRTetra and a recently identified fluorescent substrate, 4-(4-dimethylaminostyryl)- N-methyl-pyridinium (ASP+). (Journal of Biomolecular Screening 2007:436-441)

Key Words: norepinephrine • transporter • FLIPRTetra • fluorescent substrate


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[Abstract] [PDF]