The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: pathophysiology and pharmacotherapy of overactive bladder.
Overactive bladder (OAB) syndrome, which is characterized by a complex of storage symptoms (urinary urgency, frequency, nocturia, and urgency incontinence) is highly prevalent within the general population, causing major distress to patients in terms of their psychosocial and physical functioning. Muscarinic receptors of bladder smooth muscles are involved in both normal and disturbed bladder contraction. The muscarinic receptor functions may change in bladder disorders associated with OAB, implying that mechanisms, which normally have little clinical importance, may be up-regulated and contribute to the pathophysiology of OAB. In addition, several reports have suggested that various stimulations release many substances, including adenosine triphosphate, prostaglandins, nitric oxide, and acetylcholine, from bladder urothelium, which contribute to pathophysiology of the increased bladder sensation, OAB symptoms, and detrusor overactivity. Bladder urothelium possesses a non-neuronal cholinergic system and high density of muscarinic receptors. The roles and functions of the non-neuronal cholinergic system in OAB are now being evaluated. In the pharmacotherapy of OAB, antimuscarinic agents are the first choice drugs. Furthermore, new therapeutic targets at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord, and brain are proposed. In this review, the pathophysiology of OAB, especially the role of non-neuronal acetylcholine, is discussed. In addition, new drugs with new action mechanisms will be introduced.
Yoshida
Masaki
M
Department of Urology, Kumamoto Hospital of Japan Labor Health and Welfare Organization, 1670 Takehara-cho, Yatsushiro-city, Kumamoto 866-8533, Japan. akko-maki@umin.net
Masunaga
Koichi
K
Nagata
Takashi
T
Yono
Makoto
M
Homma
Yukio
Y
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine