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Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.

Alenmyr, Lisa LU ; Greiff, Lennart; Andersson, Morgan LU ; Sterner, Olov; Zygmunt, Peter LU and Högestätt, Edward LU (2012) In Basic & Clinical Pharmacology & Toxicology 110. p.264-268
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 seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen... (More)
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 seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein 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, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology
volume
110
pages
264 - 268
publisher
Wiley-Blackwell
external identifiers
  • wos:000301434300010
  • pmid:21951314
  • scopus:84857355604
ISSN
1742-7843
DOI
10.1111/j.1742-7843.2011.00803.x
language
English
LU publication?
yes
id
fe6ecc64-b3fe-49fe-a671-7f94d6edcbed (old id 2168376)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21951314?dopt=Abstract
date added to LUP
2011-10-03 14:32:26
date last changed
2017-10-22 04:52:02
@article{fe6ecc64-b3fe-49fe-a671-7f94d6edcbed,
  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 seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein 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, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was 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.},
  author       = {Alenmyr, Lisa and Greiff, Lennart and Andersson, Morgan and Sterner, Olov and Zygmunt, Peter and Högestätt, Edward},
  issn         = {1742-7843},
  language     = {eng},
  pages        = {264--268},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology},
  title        = {Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.},
  url          = {http://dx.doi.org/10.1111/j.1742-7843.2011.00803.x},
  volume       = {110},
  year         = {2012},
}