title: Effect of mucosal TRPV1 inhibition in allergic rhinitis.
abstract: Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for 7 days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 2 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5-7. Nasal peak inspiratory flow (nPIF) and eosinophil cationic protein (ECP) content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nPIF and ECP levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptoms, nasal itch or sneezes, were also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.
authors.affiliation: Clinical Chemistry and Pharmacology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Alenmyr
authors.forename: Lennart
authors.initials: L
authors.lastname: Greiff
authors.forename: Morgan
authors.initials: M
authors.lastname: Andersson
authors.forename: Olov
authors.initials: O
authors.lastname: Sterner
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
mesh_terms: D000328:Adult; D002211:Capsaicin / Q000276:immunology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005470:Fluorometry; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D011759:Pyrrolidines; C512301:SB 705498; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014508:Urea; D002211:Capsaicin