title: Comparative functional selectivity of imidafenacin and propiverine, antimuscarinic agents, for the urinary bladder over colon in conscious rats.
abstract: Antimuscarinics are the first-line choice of treatment for overactive bladder (OAB). Imidafenacin distributes in the bladder more selectively than in the submaxillary gland and colon, and hence, this drug is considered more useful for OAB than other antimuscarinics. However, the examination of imidafenacin selectivity to bladder over colon using in vivo models is limited. Thus, the author examined whether imidafenacin could induce more selective blockade of the bladder over colon in conscious rats using two pharmacological indices (colonic transit and neostigmine-induced fecal pellet output) and compared its bladder selectivity with propiverine. In the bladder study, the inhibitory doses of antimuscarinics were calculated using the area under the curve of the distension-induced rhythmic contraction in conscious rats. The relative bladder selectivity of imidafenacin to propiverine was 50-fold and 61-fold, respectively, in a dye marker colonic transit model and in a neostigmine-induced fecal pellet output model. This comparative study shows that the functional bladder selectivity of imidafenacin is higher than that of propiverine tested under the present conditions in conscious rats.
authors.affiliation: Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan. yukiko.muraki@mb.kyorin-pharm.co.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Muraki
mesh_terms: D000818:Animals; D001561:Benzilates / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D003672:Defecation / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009388:Neostigmine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
chemical_list: D001561:Benzilates; D007093:Imidazoles; D018727:Muscarinic Antagonists; D009388:Neostigmine; C015586:propiverine; C120953:imidafenacin
keywords: Antimuscarinics; Bladder selectivity; Colonic transit; Conscious rat; Imidafenacin; Overactive bladder