Overview
- Cui, M. et al. (2006) J. Neurosci. 26, 9385.
Alomone Labs A 784168 inhibits TRPV1 channels expressed in C6 cells.mTRPV1-C6 cells were loaded with Fluo-3 AM. Changes in intracellular Ca2+ were detected via changes in Fluo-3 emission following agonist application. 10 minutes pre-incubation with 0.1 µM and 1 µM A 784168 (#A-345) inhibited 1 µM capsaicin-evoked rise in intracellular Ca2+. Normalized fluorescence before and after application (arrow) of 1 µM capsaicin in cells pre-incubated with DMSO-equivalent control, 0.1 µM and 1 µM A 784168 (as indicated).
A 784168 is a synthetic and potent antagonist of the TRPV1 channel. A 784168 inhibits human TRPV1 activation by 50 nM capsaicin with an IC50 of 25 nM. A 784168 was found to produce inhibition in 1321N1 astrocytoma cells expressing recombinant human TRPV1 and also in HEK 293 cells. In addition to its inhibition of TRPV1, A 784168 was found to be a very weak antagonist of TRPM8 (IC50 = 20.8 µM) with no effect on TRPA1 channels and a variety of receptors including adenosine, angiotensin, α- and β-adrenergic receptors. A 784168 has a plasma binding capacity of 93.5±0.9% and oral bioavailability of 33%. A 784168 volume of distribution is 12.4L/kg and it has high blood-brain barrier penetrance. Administration of oral A 784168 reduces acute nociceptive behavior induced by capsaicin injection and chronic thermal hyperalgesia induced by CFA injection in a rat model1.
