title: 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. β(3)-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β(3)-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β(3)-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β(3)-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β(3)-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α(1)-Adrenoceptor antagonists (α(1)-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α(1)(A) subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α(1)(A)-adrenoceptors are additionally involved in the generation of storage symptoms. The α(1)(D) subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α(1)-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α(1)-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 α(1)-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.
authors.affiliation: Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama, Japan. yamaosa@ee.ce.nihon-u.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D058891:5-alpha Reductase Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D018727:Muscarinic Antagonists; D010726:Phosphodiesterase Inhibitors