The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept

@article{Szallasi2007TheVR,
  title={The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept},
  author={Arpad Szallasi and Daniel N. Cortright and Charles A. Blum and Samer R. Eid},
  journal={Nature Reviews Drug Discovery},
  year={2007},
  volume={6},
  pages={357-372}
}
The clinical use of TRPV1 (transient receptor potential vanilloid subfamily, member 1; also known as VR1) antagonists is based on the concept that endogenous agonists acting on TRPV1 might provide a major contribution to certain pain conditions. Indeed, a number of small-molecule TRPV1 antagonists are already undergoing Phase I/II clinical trials for the indications of chronic inflammatory pain and migraine. Moreover, animal models suggest a therapeutic value for TRPV1 antagonists in the… 

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References

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Small molecule vanilloid TRPV1 receptor antagonists approaching drug status: can they live up to the expectations?

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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 and an answer to the question how these new discoveries could be factored into TRpV1 drug discovery and development is sought.

TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications

It is now increasingly clear that TRPV1 also regulates the frequency of bladder reflex contractions, either through direct excitation of sensory fibers or through urothelial-sensory fiber cross talk involving the release of neuromediators from the epithelial cells.

Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-Induced Neuropathic Pain in the Rat

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It is described how exposure to various antagonists produces TRPV1 sensitization and a possible mechanistic explanation to that sensitization is proposed.

Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain

It is shown that TRPV1 is present on sensory neuron fibers that innervate the mouse femur and that, in an in vivo model of bone cancer pain, acute or chronic administration of a TRP V1 antagonist or disruption of the TRPv1 gene results in a significant attenuation of both ongoing and movement-evoked nocifensive behaviors.

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Good evidence suggests altered VR1 expression in various disease states, and discoveries place VR1 in a much broader perspective than pain perception and enhance the potential for unforeseen side effects, especially following prolonged vanilloid therapy.
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