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Potential Future Pharmacological Treatment of Bladder Dysfunction.
Basic Clin Pharmacol Toxicol. 2016 Oct; 119 Suppl 3:75-85.BC

Abstract

In the last decades, a number of new antimuscarinic drugs have been introduced for treatment of the overactive bladder (OAB), defined symptomatically (OAB syndrome) or urodynamically (detrusor overactivity). Recently, three new drug principles have been approved for clinical use, the β3 -adrenoceptor agonist, mirabegron, the phosphodiesterase-5 inhibitor, tadalafil and the blocker of afferent and efferent nerves, botulinum toxin. However, new alternatives are continuously being explored. OAB is a filling disorder, and ATP is involved in the generation of afferent impulses. One way of blocking the ATP afferent pathway is through the use of P2X3 receptor antagonists. In animal models, this strategy appears to work very well, but whether it translates effectively to man remains to be established. Evidence suggests that components of the endocannabinoid system are involved in regulation of bladder function. Clinical studies of cannabinoid extracts on LUTS are scarce and essentially restricted to patients with MS, and the results have so far not been convincing. Amplification of endocannabinoid activity by inhibiting their degradation via fatty acid amide hydrolase inhibitors may be an attractive approach, but no clinical experiences in OAB have been reported. Studies of the lower urinary tract have indicated that several transient receptor potential (TRP) channels, including TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1, are expressed in the bladder and may act as sensors of stretch and/or chemical irritation. Animal studies have shown that inhibition of these pathways can be effective for the reduction in bladder activity. However, the roles of these channels for normal function and in pathological states have not been established, and so far adverse effects (hyperthermia) have hampered development of antagonists.

Authors+Show Affiliations

Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA. kea@aias.au.dk. Aarhus Institute for Advanced Sciences (AIAS), Aarhus University, Aarhus, Denmark. kea@aias.au.dk.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

26990140

Citation

Andersson, Karl-Erik. "Potential Future Pharmacological Treatment of Bladder Dysfunction." Basic & Clinical Pharmacology & Toxicology, vol. 119 Suppl 3, 2016, pp. 75-85.
Andersson KE. Potential Future Pharmacological Treatment of Bladder Dysfunction. Basic Clin Pharmacol Toxicol. 2016;119 Suppl 3:75-85.
Andersson, K. E. (2016). Potential Future Pharmacological Treatment of Bladder Dysfunction. Basic & Clinical Pharmacology & Toxicology, 119 Suppl 3, 75-85. https://doi.org/10.1111/bcpt.12577
Andersson KE. Potential Future Pharmacological Treatment of Bladder Dysfunction. Basic Clin Pharmacol Toxicol. 2016;119 Suppl 3:75-85. PubMed PMID: 26990140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential Future Pharmacological Treatment of Bladder Dysfunction. A1 - Andersson,Karl-Erik, Y1 - 2016/04/06/ PY - 2015/12/22/received PY - 2016/12/23/accepted PY - 2016/10/30/pubmed PY - 2017/2/14/medline PY - 2016/3/19/entrez SP - 75 EP - 85 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin Pharmacol Toxicol VL - 119 Suppl 3 N2 - In the last decades, a number of new antimuscarinic drugs have been introduced for treatment of the overactive bladder (OAB), defined symptomatically (OAB syndrome) or urodynamically (detrusor overactivity). Recently, three new drug principles have been approved for clinical use, the β3 -adrenoceptor agonist, mirabegron, the phosphodiesterase-5 inhibitor, tadalafil and the blocker of afferent and efferent nerves, botulinum toxin. However, new alternatives are continuously being explored. OAB is a filling disorder, and ATP is involved in the generation of afferent impulses. One way of blocking the ATP afferent pathway is through the use of P2X3 receptor antagonists. In animal models, this strategy appears to work very well, but whether it translates effectively to man remains to be established. Evidence suggests that components of the endocannabinoid system are involved in regulation of bladder function. Clinical studies of cannabinoid extracts on LUTS are scarce and essentially restricted to patients with MS, and the results have so far not been convincing. Amplification of endocannabinoid activity by inhibiting their degradation via fatty acid amide hydrolase inhibitors may be an attractive approach, but no clinical experiences in OAB have been reported. Studies of the lower urinary tract have indicated that several transient receptor potential (TRP) channels, including TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1, are expressed in the bladder and may act as sensors of stretch and/or chemical irritation. Animal studies have shown that inhibition of these pathways can be effective for the reduction in bladder activity. However, the roles of these channels for normal function and in pathological states have not been established, and so far adverse effects (hyperthermia) have hampered development of antagonists. SN - 1742-7843 UR - https://www.unboundmedicine.com/medline/citation/26990140/Potential_Future_Pharmacological_Treatment_of_Bladder_Dysfunction_ L2 - https://doi.org/10.1111/bcpt.12577 DB - PRIME DP - Unbound Medicine ER -