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… Expand
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References

SHOWING 1-10 OF 197 REFERENCES
TRPV1: a therapeutic target for novel analgesic drugs?
TLDR
The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli ranging from noxious heat to endovanilloids in inflammation, and there is mounting evidence to suggest the existence of functional TRpV1 both in the brain and in various non-neuronal tissues. Expand
Small molecule vanilloid TRPV1 receptor antagonists approaching drug status: can they live up to the expectations?
  • A. Szallasi
  • Chemistry, Medicine
  • Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2006
TLDR
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. Expand
TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications
  • A. Avelino, F. Cruz
  • Chemistry, Medicine
  • Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2006
TLDR
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. Expand
Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-Induced Neuropathic Pain in the Rat
TLDR
The results suggest that TRPV4 plays a crucial role in a painful peripheral neuropathy, making it a very promising target for the development of a novel class of analgesics. Expand
The transient receptor potential vanilloid 1: role in airway inflammation and disease.
TLDR
Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRpV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. Expand
Attenuation of experimental arthritis in TRPV1R knockout mice.
TLDR
It is suggested that TRPV1 receptors are important for the development of joint inflammation and the associated mechanical hypersensitivity observed in this model. Expand
Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist
TLDR
SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPv1 antagonists, and may prove to be a useful tool to further study the biology of TRpV1. Expand
The TRPV1 receptor: target of toxicants and therapeutics.
  • B. Veronesi, M. Oortgiesen
  • Medicine, Chemistry
  • Toxicological sciences : an official journal of the Society of Toxicology
  • 2006
TLDR
It is described how exposure to various antagonists produces TRPV1 sensitization and a possible mechanistic explanation to that sensitization is proposed. Expand
Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain
TLDR
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. Expand
TRPV1b, a Functional Human Vanilloid Receptor Splice Variant
TLDR
A novel human TRpV1 RNA splice variant, TRPV1b, which forms functional ion channels that are activated by temperature (threshold, ∼47°C), but not by capsaicin or protons, is identified. Expand
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