Advances in the design and therapeutic use of capsaicin receptor TRPV1 agonists and antagonists

Abstract

Background: The capsaicin receptor TRPV1 is a polymodal nociceptor expressed predominantly on sensory neurons. Pharmacological blockade of TRPV1 by antagonists and desensitization of TRPV1 by agonists represent alternative therapeutic strategies for the treatment of various medical conditions, including chronic pain. Objectives and methods: A vast patent literature (> 1,000 patents) disclosing both natural and synthetic molecules as TRPV1 agonist and antagonist exists. A comprehensive review of the TRPV patent literature is out of the scope of this paper. Instead, it focuses on recent advances in the potential use of TRPV1 agonists and antagonists for therapeutic purposes. In particular, this review attempts to collate these patents according to the chemical classes they disclose and discusses the structure–activity relationships that best bring out their therapeutic potential. Results/conclusion: A wide range of TRPV1 drug formulations (per os, topical and site-specific injectable) is expected to enter the clinical practice for indications as wide as chronic pain, overactive bladder, chronic cough, obesity, diabetes and, possibly, cancer as well as neurological and psychiatric disorders.

Keywords::

• antagonist
• capsaicin
• ion channel
• pain
• TRPV1
• vanilloid