The transient receptor potential vanilloid-1 cat ion channel (TRPV1) is a nonspecific cation channel that can be
activated by multiple endogenous stimuli and is expressed predominantly in sensory neurons, where it serves as a key
nodal point in pain transmission pathways. In mammals, TRPV1 displays a wide tissue and cellular expression including
both the peripheral and central nervous system, and in the latter it is now recognized to have a broader distribution and
function. The pharmacological modulation of TRPV1 represents a strategy for the treatment of a variety of disease states,
particularly those requiring chronic pain management. The validation of the TRPV1 channel as a therapeutic target for the
control of pain and inflammatory conditions in a variety of diseases and injury states, has prompted the development of
several TRPV1 agonists and antagonists that have entered clinical trials. Studies comparing the analgesic effects of
TRPV1 antagonists with and without significant CNS penetration demonstrated that a dual (both peripheral and central)
action is required to produce broad-spectrum analgesia. TRPV1 can be considered as a target for next generation analgesics.
However, although a number of compounds are in clinical trials, the therapeutic utility of TRPV1 agonist and antagonists
is yet to be validated unequivocally. This review summarizes current clinical trials and recent patents with small
molecule TRPV1 agonists and antagonists with a focus on neurological conditions.
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, Pozzuoli, Italy.