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

  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},
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… 

Drug design and development through the vanilloid receptor

New findings indicate that TRPV1 is tonically active in physiological conditions and its pharmacological blockade leads to hyperthermia, and the full abrogation of TRpV1 in some models of chronic pain results in enhanced pain.

Transient receptor potential vanilloid-1 antagonists: a survey of recent patent literature

This review summarizes patent literature and progress in defining the utility of small molecule TRPV1 antagonists during 2008 – 2009 and attests to the sustained interest in the TRpV1 class of therapeutics.

Medicinal chemistry of the vanilloid (Capsaicin) TRPV1 receptor: current knowledge and future perspectives

In this review article, the medicinal chemistry of TRPV1 antagonists is discussed inasmuch as it relates to the efficacy, safety, tolerability and potential side effects of these compounds.

Screening TRPV1 antagonists for the treatment of pain: lessons learned over a decade

An encouraging advance is the dissection of therapeutic efficacy of antagonists from induction of hyperthermia, a side effect that initially had raised concerns about the suitability of systemically administered TRPV1 antagonists for therapy.

Transient receptor potential vanilloid type 1 antagonists: a patent review (2011 – 2014)

This review article covers the patents that claim TRPV1 antagonists and were published during 2011 – 2014 and describes the representative chemical entities with important in vitro and in vivo data.

TRPV1-Targeted Drugs in Development for Human Pain Conditions

While the analgesic pharmacopeia for chronic pain patients is ancient and poorly effective, modern TRPV1-targeted drugs could rapidly become available as the next generation of analgesics for a broad spectrum of pain conditions.

TRPV1: A Potential Drug Target for Treating Various Diseases

The roles of TRPV1 in the normal physiology and pathophysiology of selected organs of the body are described and how drugs targeting this channel could be important clinically are highlighted.



TRPV1: a therapeutic target for novel analgesic drugs?

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

  • A. Szallasi
  • Biology
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2006
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

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.

Attenuation of experimental arthritis in TRPV1R knockout mice.

The TRPV1 receptor: target of toxicants and therapeutics.

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.

Vanilloid (capsaicin) receptors in health and disease.

  • A. Szallasi
  • Biology
    American journal of clinical pathology
  • 2002
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.