Antimuscarinics and overactive bladder: other mechanism of action.
Antimuscarinics are considered first-line treatment for patients with overactive bladder (OAB). However, the mechanism by which antimuscarinics improve the symptoms of OAB remains to be elucidated. Animal studies suggest that antimuscarinics may exert an inhibitory effect on afferent nerves without an effect on detrusor contraction. A release of acetylcholine from the urothelium has been demonstrated in isolated human bladder. In addition, muscarinic receptors (MRs) were found in the urothelium and suburothelial myofibroblasts, suggesting a role for MR mechanisms in urothelial sensory function. Acetylcholine released during the storage phase could be expected to enhance the myogenic contractile activity of the detrusor, which can generate afferent signals. It is suggested that antimuscarinics may decrease bladder afferent activity by blocking MR in the above sites, thereby improving OAB symptoms.
Yamaguchi
Osamu
O
Department of Urology, Fukushima Medical University, School of Medicine, Hikarigaoka-1, Fukushima, Japan. yamaosa@fmu.ac.jp
D000109:Acetylcholine / Q000378:metabolism; D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012677:Sensation; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine