High-throughput screening for norepinephrine transporter inhibitors using the FLIPRTetra.
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 FLIPR(Tetra) and a recently identified fluorescent substrate, 4-(4-dimethylaminostyryl)- N-methyl-pyridinium (ASP(+)).
Wagstaff
Ryan
R
Department of Pharmacology & Lead Discovery, Neurocrine Bisciences, Inc., San Diego, California 92130, USA.
Hedrick
Michael
M
Fan
Jun
J
Crowe
Paul D
PD
DiSepio
Daniel
D
D018759:Adrenergic Uptake Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011726:Pyridinium Compounds
C032315:4-(4-dimethylaminostyryl)-1-methylpyridinium; D018759:Adrenergic Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011726:Pyridinium Compounds