TRPV1 Antagonists as a Potential Treatment for Hyperalgesia

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Abstract:

The vanilloid receptor (TRPV1) is a member of the transient receptor potential family of ion channels that is highly expressed in nociceptive primary afferent sensory neurons. TRPV1 is a voltage-dependent cation channel, which can be activated at physiological membrane potentials by stimuli including noxious heat (>42 degrees), capsaicin, hydrogen ions and anandamide. Activation of TRPV1 results in release of neurotransmitters from peripheral and central nerve terminals, resulting in pain and inflammation. Endogenous inflammatory mediators also promote activation of TRPV1. Studies in TRPV1 null mice reveal that responses to noxious heat stimuli are normal but the development of thermal hyperalgesia is abolished. Several TRPV1 antagonists have recently been developed and reported to alleviate or reverse mechanical and thermal hyperalgesia associated with inflammatory pain. This review will examine the development of patented TRPV1 antagonists as a potential clinical treatment for the alleviation of pain associated with hyperalgesia and inflammation.





Keywords: TRPV1; antagonist; capsaicin; hyperalgesia; inflammation; pain; sensory neuron

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/157488906775245309

Affiliations: Pain Management Research Institute, Kolling Institute, Level 4, Main Block, University of Sydney at Royal North Shore Hospital, E25. St. Leonards, NSW 2065, Sydney, Australia;

Publication date: January 1, 2006

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  • Recent Patents on CNS Drug Discovery publishes review articles on recent patents in the field of CNS drug discovery e.g. novel bioactive compounds, analogs & targets. A selection of important and recent patents on CNS drug discovery is also included in the journal. The journal is essential reading for all researchers involved in CNS drug design and discovery.
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