New targets for overactive bladder—ICI-RS 2109
Fry, Christopher Henry ; Chakrabarty, Basu ; Hashitani, Hikaru ; Andersson, Karl Erik LU
; McCloskey, Karen
; Jabr, Rita I
and Drake, Marcus J.
(2020)
In Neurourology and Urodynamics
39(S3).
p.113-121
- Abstract
Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and... (More)
Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and TRPM4) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+-activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
(Less)
- author
- Fry, Christopher Henry
; Chakrabarty, Basu
; Hashitani, Hikaru
; Andersson, Karl Erik
LU
; McCloskey, Karen
; Jabr, Rita I
and Drake, Marcus J.
- organization
- publishing date
- 2020-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cyclic nucleotides, fibrosis, small conductance K channels, TRP channels, β-agonists
- in
- Neurourology and Urodynamics
- volume
- 39
- issue
- S3
- pages
- 9 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:31737931
- scopus:85075356984
- ISSN
- 0733-2467
- DOI
- 10.1002/nau.24228
- language
- English
- LU publication?
- yes
- id
- 3672539b-c82b-431b-8ee4-7b39fd2c4045
- date added to LUP
- 2019-12-11 09:34:22
- date last changed
- 2024-04-17 00:53:57
@article{3672539b-c82b-431b-8ee4-7b39fd2c4045,
abstract = {{<p>Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β<sub>3</sub> agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV<sub>1</sub>, TRPV<sub>4</sub>, TRPA<sub>1</sub>, and TRPM<sub>4</sub>) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.</p>}},
author = {{Fry, Christopher Henry and Chakrabarty, Basu and Hashitani, Hikaru and Andersson, Karl Erik and McCloskey, Karen and Jabr, Rita I and Drake, Marcus J.}},
issn = {{0733-2467}},
keywords = {{cyclic nucleotides; fibrosis; small conductance K channels; TRP channels; β-agonists}},
language = {{eng}},
number = {{S3}},
pages = {{113--121}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Neurourology and Urodynamics}},
title = {{New targets for overactive bladder—ICI-RS 2109}},
url = {{http://dx.doi.org/10.1002/nau.24228}},
doi = {{10.1002/nau.24228}},
volume = {{39}},
year = {{2020}},
}