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Agents in early development for treatment of bladder dysfunction - promise of drugs acting at TRP channels?
Expert Opin Investig Drugs. 2019 Sep; 28(9):749-755.EO

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 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.

Authors+Show Affiliations

Institute for Regenerative Medicine, Wake Forest University School of Medicine , Winston Salem , NC , USA. Institute of Laboratory Medicine, Lund University , Lund , Sweden.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31399015

Citation

Andersson, Karl-Erik. "Agents in Early Development for Treatment of Bladder Dysfunction - Promise of Drugs Acting at TRP Channels?" Expert Opinion On Investigational Drugs, vol. 28, no. 9, 2019, pp. 749-755.
Andersson KE. Agents in early development for treatment of bladder dysfunction - promise of drugs acting at TRP channels? Expert Opin Investig Drugs. 2019;28(9):749-755.
Andersson, K. E. (2019). Agents in early development for treatment of bladder dysfunction - promise of drugs acting at TRP channels? Expert Opinion On Investigational Drugs, 28(9), 749-755. https://doi.org/10.1080/13543784.2019.1654994
Andersson KE. Agents in Early Development for Treatment of Bladder Dysfunction - Promise of Drugs Acting at TRP Channels. Expert Opin Investig Drugs. 2019;28(9):749-755. PubMed PMID: 31399015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Agents in early development for treatment of bladder dysfunction - promise of drugs acting at TRP channels? A1 - Andersson,Karl-Erik, Y1 - 2019/08/14/ PY - 2019/8/11/pubmed PY - 2019/10/28/medline PY - 2019/8/11/entrez KW - Lower urinary tract KW - TRPA1 KW - TRPM4 KW - TRPM8 KW - TRPV1 KW - TRPV4 KW - bladder pain KW - overactive bladder KW - underactive bladder SP - 749 EP - 755 JF - Expert opinion on investigational drugs JO - Expert Opin Investig Drugs VL - 28 IS - 9 N2 - 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. SN - 1744-7658 UR - https://www.unboundmedicine.com/medline/citation/31399015/Agents_in_early_development_for_treatment_of_bladder_dysfunction___promise_of_drugs_acting_at_TRP_channels L2 - https://www.tandfonline.com/doi/full/10.1080/13543784.2019.1654994 DB - PRIME DP - Unbound Medicine ER -