TRPV1 (vanilloid receptor, capsaicin receptor) agonists and antagonists

The vanilloid receptors (TRPVs) are a family of cation channels expressed both in neural and non-neural cells, which act as sensors for a variety of physical (heat, osmolarity) and ionic (increase of acidity, depletion of calcium stores) stimuli. As a druggable integrator of noxious signals and the target of the hot dietary alkaloid capsaicin, TRPV1 (vanilloid receptor 1, capsaicin receptor) has so far overshadowed the other vanilloid receptors. Ligand gating of TRPV1 is provided by a heterogeneous group of compounds named vanilloids, of which two prototypes (N-acylphenolamines and homovanillates) have been extensively investigated. Inhibition of vanilloid activity underlies the therapeutic application of vanilloids in a variety of diseases, such as chronic pain, bladder disorders and cough, and can be achieved by desensitisation or by antagonism. Both strategies have been pursued, resulting in the discovery of some promising compounds which have entered clinical trials.