Karl-Erik Andersson1, Christopher Fry2, Jalesh Panicker3, Kevin Rademakers3. 1. Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem NC, and Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. 2. Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, London, United Kingdom. 3. Department of urology, Maastricht University Medical Center, Maastricht, The Netherlands.
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.
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.
Authors: Mafalda S L Aresta Branco; Alejandro Gutierrez Cruz; Jacob Dayton; Brian A Perrino; Violeta N Mutafova-Yambolieva Journal: Front Physiol Date: 2022-06-16 Impact factor: 4.755
Authors: Bingsheng Li; Qingfeng Yu; Ruixiao Wang; Christian Gratzke; Xiaolong Wang; Annabel Spek; Annika Herlemann; Alexander Tamalunas; Frank Strittmatter; Raphaela Waidelich; Christian G Stief; Martin Hennenberg Journal: Front Pharmacol Date: 2020-04-07 Impact factor: 5.810