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Agents in early development for treatment of bladder dysfunction–promise of drugs acting at TRP channels?

Andersson, Karl Erik LU orcid (2019) In Expert Opinion on Investigational Drugs 28(9).
Abstract

Introduction: In the lower urinary tract (LUT) several members of the TRP superfamily are involved in nociception and mechanosensory transduction. Animal studies have suggested a therapeutic potential of some of these channels, including TRPV1, TRPV4, TRPM8, TRPA1, and TRPM4, for treatment of bladder over- and underactivity and bladder pain disorders, but translation of this information to clinical application has been slow. Areas covered: An update on and discussion of current information on the potential clinical use of TRP channel agonists/antagonists in the treatment of different types of bladder dysfunction. The electronic databases PubMed and Scopus were used to identify relevant clinical and animal studies. Expert opinion: The... (More)

Introduction: In the lower urinary tract (LUT) several members of the TRP superfamily are involved in nociception and mechanosensory transduction. Animal studies have suggested a therapeutic potential of some of these channels, including TRPV1, TRPV4, TRPM8, TRPA1, and TRPM4, for treatment of bladder over- and underactivity and bladder pain disorders, but translation of this information to clinical application has been slow. Areas covered: An update on and discussion of current information on the potential clinical use of TRP channel agonists/antagonists in the treatment of different types of bladder dysfunction. The electronic databases PubMed and Scopus were used to identify relevant clinical and animal studies. Expert opinion: The therapeutic effect of TRPV1 channel desensitizing agonists (capsaicin, resiniferatoxin, given intravesically) has been convincingly demonstrated in some forms of bladder overactivity. However, so far, the potential of any of the small-molecule TRP channel blockers developed for non-bladder indications and tested in early human trials for safety has not been explored clinically in LUT dysfunction. The adverse effects of hyperthermia and reduction of noxious heat sensation of the first generation TRPV1 blockers have delayed development. Despite lack of translational information, TRP channels remain interesting targets for future LUT drugs.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bladder pain, Lower urinary tract, overactive bladder, TRPA1, TRPM4, TRPM8, TRPV1, TRPV4, underactive bladder
in
Expert Opinion on Investigational Drugs
volume
28
issue
9
pages
749 pages
publisher
Ashley Publications
external identifiers
  • scopus:85070866891
  • pmid:31399015
ISSN
1354-3784
DOI
10.1080/13543784.2019.1654994
language
English
LU publication?
yes
id
f096acca-f40e-4a94-b419-37e6ce4d37f8
date added to LUP
2019-09-05 15:19:56
date last changed
2024-05-30 02:03:27
@article{f096acca-f40e-4a94-b419-37e6ce4d37f8,
  abstract     = {{<p>Introduction: In the lower urinary tract (LUT) several members of the TRP superfamily are involved in nociception and mechanosensory transduction. Animal studies have suggested a therapeutic potential of some of these channels, including TRPV1, TRPV4, TRPM8, TRPA1, and TRPM4, for treatment of bladder over- and underactivity and bladder pain disorders, but translation of this information to clinical application has been slow. Areas covered: An update on and discussion of current information on the potential clinical use of TRP channel agonists/antagonists in the treatment of different types of bladder dysfunction. The electronic databases PubMed and Scopus were used to identify relevant clinical and animal studies. Expert opinion: The therapeutic effect of TRPV1 channel desensitizing agonists (capsaicin, resiniferatoxin, given intravesically) has been convincingly demonstrated in some forms of bladder overactivity. However, so far, the potential of any of the small-molecule TRP channel blockers developed for non-bladder indications and tested in early human trials for safety has not been explored clinically in LUT dysfunction. The adverse effects of hyperthermia and reduction of noxious heat sensation of the first generation TRPV1 blockers have delayed development. Despite lack of translational information, TRP channels remain interesting targets for future LUT drugs.</p>}},
  author       = {{Andersson, Karl Erik}},
  issn         = {{1354-3784}},
  keywords     = {{bladder pain; Lower urinary tract; overactive bladder; TRPA1; TRPM4; TRPM8; TRPV1; TRPV4; underactive bladder}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Ashley Publications}},
  series       = {{Expert Opinion on Investigational Drugs}},
  title        = {{Agents in early development for treatment of bladder dysfunction–promise of drugs acting at TRP channels?}},
  url          = {{http://dx.doi.org/10.1080/13543784.2019.1654994}},
  doi          = {{10.1080/13543784.2019.1654994}},
  volume       = {{28}},
  year         = {{2019}},
}