Promising therapeutic targets for the treatment of urine storage dysfunction : what’s the status?
Andersson, Karl Erik LU
(2024)
In Expert Opinion on Therapeutic Targets
- Abstract
Introduction: Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction. Areas covered: In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2 × 3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide–dependent pathways, and MaxiK±channel–gene therapy. Expert opinion: TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists. This has so far precluded their application to urine storage disorders. Other TRP channel blockers with promising rationale have yet to be tested on the human... (More)
Introduction: Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction. Areas covered: In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2 × 3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide–dependent pathways, and MaxiK±channel–gene therapy. Expert opinion: TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists. This has so far precluded their application to urine storage disorders. Other TRP channel blockers with promising rationale have yet to be tested on the human lower urinary tract. The P2 × 3receptor antagonist, eliapixant, was tested in a randomized controlled clinical trial, was well tolerated but did not meet clinical efficacy endpoints. Antifibrosis agent still await application to the human lower urinary tract. New drug principles for oxidative stress, purine nucleoside phosphorylase inhibition, and NOX inhibition are still at an experimental stage, and so are soluble guanylate cyclase stimulators. Gene therapy with MaxiK±channels is still an interesting approach but no new trials seem to be in pipeline.
(Less)
- author
- Andersson, Karl Erik
LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- in press
- subject
- keywords
- antifibrosis, detrusor overactivity, Lower urinary tract symptoms, MaxiK±channels, overactive bladder syndrome, oxidative stress, P2X3 receptors, soluble guanylate cyclase stimulators, TRP channels
- in
- Expert Opinion on Therapeutic Targets
- publisher
- Ashley Publications
- external identifiers
-
- pmid:38629152
- scopus:85191163621
- ISSN
- 1472-8222
- DOI
- 10.1080/14728222.2024.2344698
- language
- English
- LU publication?
- yes
- id
- e719c4e0-0047-4d1a-9873-d129bd3189fb
- date added to LUP
- 2024-05-06 09:03:46
- date last changed
- 2024-05-20 11:18:16
@article{e719c4e0-0047-4d1a-9873-d129bd3189fb,
abstract = {{<p>Introduction: Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction. Areas covered: In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2 × 3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide–dependent pathways, and MaxiK±channel–gene therapy. Expert opinion: TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists. This has so far precluded their application to urine storage disorders. Other TRP channel blockers with promising rationale have yet to be tested on the human lower urinary tract. The P2 × 3receptor antagonist, eliapixant, was tested in a randomized controlled clinical trial, was well tolerated but did not meet clinical efficacy endpoints. Antifibrosis agent still await application to the human lower urinary tract. New drug principles for oxidative stress, purine nucleoside phosphorylase inhibition, and NOX inhibition are still at an experimental stage, and so are soluble guanylate cyclase stimulators. Gene therapy with MaxiK±channels is still an interesting approach but no new trials seem to be in pipeline.</p>}},
author = {{Andersson, Karl Erik}},
issn = {{1472-8222}},
keywords = {{antifibrosis; detrusor overactivity; Lower urinary tract symptoms; MaxiK±channels; overactive bladder syndrome; oxidative stress; P2X3 receptors; soluble guanylate cyclase stimulators; TRP channels}},
language = {{eng}},
publisher = {{Ashley Publications}},
series = {{Expert Opinion on Therapeutic Targets}},
title = {{Promising therapeutic targets for the treatment of urine storage dysfunction : what’s the status?}},
url = {{http://dx.doi.org/10.1080/14728222.2024.2344698}},
doi = {{10.1080/14728222.2024.2344698}},
year = {{2024}},
}