Therapeutic Modulation of Urinary Bladder Function: Multiple Targets at Multiple Levels

• Published in: Annual review of pharmacology and toxicology Vol. 55; no. 1; pp. 269 - 287
• Main Author: Michel, Martin C
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 06.01.2015
• Subjects: Adrenergic alpha-1 Receptor Antagonists - therapeutic use; Adrenergic beta-Agonists - therapeutic use; adrenoceptor antagonist; afferent nerve; Animals; Central Nervous System - drug effects; Central Nervous System - metabolism; Central Nervous System - physiopathology; Humans; Muscarinic Antagonists - therapeutic use; muscarinic receptor antagonist; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - metabolism; Muscle, Smooth - physiopathology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurons, Efferent - drug effects; Neurons, Efferent - metabolism; Signal Transduction - drug effects; Treatment Outcome; Urinary Bladder - drug effects; Urinary Bladder - innervation; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary Bladder - physiopathology; Urinary Bladder Diseases - diagnosis; Urinary Bladder Diseases - drug therapy; Urinary Bladder Diseases - metabolism; Urinary Bladder Diseases - physiopathology; Urodynamics - drug effects; Urological Agents - adverse effects; Urological Agents - therapeutic use; urothelium; Urothelium - drug effects; Urothelium - innervation; Urothelium - metabolism; Urothelium - physiopathology; β-adrenoceptor agonist; β-adrenoceptor agonist; muscarinic receptor antagonist; urothelium; afferent nerve; α1-adrenoceptor antagonist
• ISSN: 0362-1642; 1545-4304
• DOI: 10.1146/annurev-pharmtox-010814-124536

Storage dysfunction of the urinary bladder, specifically overactive bladder syndrome, is a condition that occurs frequently in the general population. Historically, pathophysiological and treatment concepts related to overactive bladder have focused on smooth muscle cells. Although these are the central effector, numerous anatomic structures are involved in their regulation, including the urothelium, afferent and efferent nerves, and the central nervous system. Each of these structures involves receptors for-and the urothelium itself also releases-many mediators. Moreover, hypoperfusion, hypertrophy, and fibrosis can affect bladder function. Established treatments such as muscarinic antagonists, β-adrenoceptor agonists, and onabotulinumtoxinA each work in part through their effects on the urothelium and afferent nerves, as do α 1 -adrenoceptor antagonists in the treatment of voiding dysfunction associated with benign prostatic hyperplasia; however, none of these treatments are specifically targeted to the urothelium and afferent nerves. It remains to be explored whether future treatments that specifically act at one of these structures will provide a therapeutic advantage.