Vanilloid receptor-1 (TRPV1) is a nonselective cation channel,
predominantly expressed by sensory neurons, which plays a
key role in the detection of noxious painful stimuli such as
capsaicin, acid, and heat. TRPV1 antagonists may represent
novel therapeutic agents for the treatment of a range of conditions
including chronic pain, migraine, and gastrointestinal
Vanilloid receptor 1 (TRPV1) is activated by chemical ligands and heat. In this study, we found that each of the group B antagonists competed with and prevented BCTC, AMG6880 or AMG7472 antagonism of rat TRPV1 activation by protons with pA2 values similar to those for blocking capsaicin, indicating that proton activation does not alter the conformation of the TRPV1 capsaicin-binding pocket. In conclusion, group A antagonists seem to lock the channel conformation in the closed state, blocking both capsaicin and proton activation.
The vanilloid receptor transient receptor potential type V1 (TRPV1) integrates responses to multiple stimuli, such as capsaicin, acid, heat, and endovanilloids and plays an important role in the transmission of inflammatory pain. Here, we report the identification and in vitro characterization of A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel, potent, and selective TRPV1 antagonist.