Advances in the development of TRPV1 antagonists

Transient receptor potential V1 (TRPV1) is a nonspecific cation channel subject to polymodal activation. TRPV1, originally termed vanilloid receptor 1, can be activated by the prototypical vanilloid capsaicin as well as decreases in extracellular pH and increases in temperature. The neuronal expression and biology surrounding TRPV1 suggest that it plays a significant role in the establishment and maintenance of various pain states as well as a potential role for TRPV1 in cough and bladder function. This review outlines the potential mechanism(s) by which activation of TRPV1 leads to pain and hyperalgesia, lessons learned via the development of antagonists and the current status of the development of therapeutic entities for validation within a clinical setting.