title: Vanilloid receptors: new insights enhance potential as a therapeutic target.
abstract: Compounds related to capsaicin and its ultrapotent analog, resiniferatoxin (RTX), collectively referred to as vanilloids, interact at a specific membrane recognition site (vanilloid receptor), expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation. Desensitization to vanilloids is a promising therapeutic approach to mitigate neuropathic pain and pathological conditions (e.g. vasomotor rhinitis) in which neuropeptides released from primary sensory neurons play a major role. Capsaicin-containing preparations are already commercially available for these purposes. The use of capsaicin, however, is severely limited by its irritancy, and the synthesis of novel vanilloids with an improved pungency/desensitization ratio is an on-going objective. This review highlights the emerging evidence that the vanilloid receptor is not a single receptor but a family of receptors, and that these receptors recognize not simply RTX and capsaicin structural analogs but are broader in their ligand-binding selectivity. We further focus on ligand-induced messenger plasticity, a recently discovered mechanism underlying the analgesic actions of vanilloids. Lastly, we give a brief overview of the current clinical uses of vanilloids and their future therapeutic potential. The possibility is raised that vanilloid receptor subtype-specific drugs may be synthesized, devoid of the undesirable side-effects of capsaicin.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Szallasi
authors.forename: P M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000627:therapeutic use*; D004224:Diterpenes / Q000627:therapeutic use*; D015536:Down-Regulation; D006801:Humans; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects*; D013329:Structure-Activity Relationship; D015854:Up-Regulation
chemical_list: D004224:Diterpenes; C087847:Phax protein, rat; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; C024353:resiniferatoxin; D002211:Capsaicin