New targets for overactive bladder—ICI‐RS 2109

Fry, Christopher Henry, Chakrabarty, Basu, Hashitani, Hikaru, Andersson, Karl‐Erik, McCloskey, Karen, Jabr, Rita I. and Drake, Marcus J. (2020) New targets for overactive bladder—ICI‐RS 2109 Neurourology and Urodynamics, 39 (S3).

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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 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.

Item Type:	Article
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Fry, Christopher Henry C.H.Fry@surrey.ac.uk Chakrabarty, Basu Hashitani, Hikaru Andersson, Karl‐Erik McCloskey, Karen Jabr, Rita I. rita.jabr@surrey.ac.uk Drake, Marcus J.
Date :	14 July 2020
DOI :	10.1002/nau.24228
Uncontrolled Keywords :	Cyclic nucleotides; Fibrosis small conductance K+ channels; TRP channels; β3‐agonists
Additional Information :	Supplement: ICI‐RS 2019
Depositing User :	Clive Harris
Date Deposited :	01 Oct 2020 14:49
Last Modified :	01 Oct 2020 14:50
URI:	http://epubs.surrey.ac.uk/id/eprint/858616

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