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.
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.