Which molecular targets do we need to focus on to restore voiding function? ICI‐RS 2017

KE Andersson, Christopher Fry, JN Panicker, Kevin L.J. Rademakers

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Aims

Update on some molecular targets for new drugs to improve lower urinary tract (LUT) dysfunction.

Methods

Using PubMed, a search for literature on molecular targets in the LUT was performed to identify relevant clinical and animal studies. Keywords were entered as Medical Subject Headings (MeSH) or as text words. The Mesh terms were used in various combinations and usually included the terms lower urinary AND pharmacology. Other Mesh term included: bladder, urethra, CNS, physiology, afferent activity, ATP, prostanoids, cannabinoids, fibrosis. Search results were assessed for their overall relevance to this review.

Results

In a normal bladder, ATP contributes little to detrusor contraction, but in a diseased bladder ATP may contribute to OAB. Selective decrease of ATP release via adenosine A1 receptor stimulation offers a potential treatment possibility. Candidates for relaxation of the smooth muscle of the urethra can be found among, for example, the receptor subtypes of PGE2, and PGD2. Drugs for relaxation of the striated sphincter can target the muscle directly or the spinal sphincter control. Fibrosis is a major problem in LUT dysfunction and agents with an inhibitory effect on the TGFβ pathway, for example relaxin and BMP7, may be promising avenues. Available drugs with a CNS site of action are often limited by low efficacy or adverse effects. Inhibitors of the glycine receptor Gly‐T2 or antagonists of the adenosine A2 receptor may be new alternatives.

Conclusion

New molecular targets for drugs aiming at improvement of voiding function can be identified, but their translational impact remains to be established.

Original languageEnglish
Pages (from-to)S117-S126
Number of pages10
JournalNeurourology and Urodynamics
Volume37
Issue numberS4
Early online date31 Jul 2018
DOIs
Publication statusPublished - 31 Jul 2018

Bibliographical note

Supplement: International Consultation on Incontinence Research Society, Papers from the 7th Meeting, 8th to 10th June 2017

Keywords

  • ATP
  • bladder
  • cannabinoids
  • CNS
  • fibrosis
  • prostanoids
  • urethra

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