Nonvanilloid TRPV1 Antagonists
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 18 5835
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noside (100 µM) was added for the first 2 days to kill dividing
nonneuronal cells.
Uptake Assays. Terasaki plates containing DRG neurons
grown for 3 days were equilibrated with four washes of HEPES
(10 mM, pH 7.4)-buffered calcium- and magnesium-free Hank’s
balanced salt solution. The solution in each well was removed
from the individual wells. For antagonistic studies, medium
(10 µL) containing 10 µCi/ml 45Ca2+ and 0.5 M capsaicin
together with the test concentration of the compound was
added to each well. The neurons were incubated at room
temperature for 10 min, and then the Terasaki plates were
washed six times in HEPES (10 mM, pH 7.4)-buffered calcium-
and magnesium-free Hank’s balanced salt solution and dried
in an oven. Sodium dodecyl sulfate (0.3%, 10 µL) was then
added to dissolve the cells and extract the 45Ca2+. The contents
of each well were transferred to scintillation vials and counted
in 3 mL of Aquasol-2 scintillant. Antagonistic activities of test
compounds were given as IC50 (the concentration of the
compound necessary to reduce the response to 0.5 µM capsaicin
by 50%). The IC50 values were estimated at least three
replicates at each concentrated. Each compound was tested
at least in two independent experiments.
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Acknowledgment. This work was supported by a
grant 02-PJ2-PG4-PT01-0014 from the Korean ministry
of Health & Welfare.
Supporting Information Available: Elemental analysis
data. This material is available free of charge via the Internet
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