Abstract
The cloning of the transient receptor potential vanilloid type-1 (TRPV1) receptor initiated the discovery of potent small molecule antagonists, many of which are in preclinical phase or already undergoing clinical trials. While animal experiments imply a therapeutic value for these compounds as novel analgesic-antiphlogistic drugs, new findings with TRPV1 deficient (trpv1 -/-) mice signal troubles for TRPV1 antagonists as clinical research gains impetus. An emerging concept with important implications for drug development is that TRPV1 may be differentially regulated under physiological and pathological conditions. If so, it is conceivable that such TRPV1 ligands can be synthesized that specifically target TRPV1 in diseased (e.g. inflamed or neoplastic) tissues but spare TRPV1 that subserves its physiological functions in healthy organs. This review explores the current status of this field and seeks an answer to the question how these new discoveries could be factored into TRPV1 drug discovery and development.
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