Latest treatment for lower urinary tract dysfunction: Therapeutic agents and mechanism of action - Abstract

Recent studies suggest that antimuscarinics might suppress bladder afferent activity by blocking muscarinic receptors in the urothelium, myofibroblasts and detrusor, thereby improving overactive bladder symptoms.

β3 -Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β3 -Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β3 -adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β3 -adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β3 -adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α1 -Adrenoceptor antagonists (α1 -blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α1A subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α1A -adrenoceptors are additionally involved in the generation of storage symptoms. The α1D subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α1 -Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α1 -blockers and antimuscarinics has been recommended. Treatment with 5α-reductase inhibitor for 1 year improves urinary symptoms and flow rate by reducing prostatic volume in men with benign prostatic enlargement. A pooled analysis showed that the long-term (2 or 4 years) treatment with 5α-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5α-reductase inhibitor and α1 -blocker was shown to provide a rapid improvement in lower urinary tract symptoms, and reduce the relative risk of acute urinary retention and benign prostatic hyperplasia-related surgery. Phosphodiesterase inhibitors might target a nitric oxide-cyclic guanosine monophosphate pathway in the prostate, urethra and bladder. Phosphodiesterase-5 inhibitors (sildenafil or tadalafil) were shown to provide clinically relevant improvements in both male lower urinary tract symptoms and erectile dysfunction.

Written by:
Yamaguchi O.   Are you the author?
Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama, Japan.

Reference: Int J Urol. 2012 Nov 28. Epub ahead of print.
doi: 10.1111/iju.12008

PubMed Abstract
PMID: 23190275 Overactive Bladder (OAB) Section