Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI-RS 2017

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.

Keywords: ATP; CNS; bladder; cannabinoids; fibrosis; prostanoids; urethra.