Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2168376
- author
- Alenmyr, Lisa LU ; Greiff, Lennart ; Andersson, Morgan LU ; Sterner, Olov ; Zygmunt, Peter LU and Högestätt, Edward LU
- organization
- publishing date
- 2012
- 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
- pmid:21951314
- 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
- 2016-04-04 07:29:11
- date last changed
- 2022-03-15 07:03:36
@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}}, doi = {{10.1111/j.1742-7843.2011.00803.x}}, volume = {{110}}, year = {{2012}}, }