title: Anticholinergic therapy for overactive bladder: a nicotinic modality?
abstract: Until recently the treatment of Overactive Bladder (OAB) has primarily been aimed at mitigating hypercholinergic activity in the bladder via antagonism of muscarinic acetylcholine receptors. However, antimuscarinic therapies have limited efficacy and significant side effects. It is now known that nicotinic acetylcholine receptor (nAChR) subtypes are expressed in the urothelium and on afferent nerve fibers in the bladder, and it is believed that these receptors serve to communicate urgency and facilitate voiding function. This presents the opportunity for an alternative to the antimuscarinic approach, one which involves inhibition of nAChRs in the bladder that are chronically overstimulated by acetylcholine. Specifically, we hypothesize that an orally administered nAChR-selective inhibitor with extensive renal elimination will result in higher local concentrations in the bladder and lower systemic exposure than current therapies, representing a novel targeted approach to the treatment of OAB with a more favorable side effect profile.
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Targacept, Inc., Winston-Salem, NC 27101, USA. Steven.Toler@Targacept.com
authors.forename: Steven M
authors.initials: SM
authors.lastname: Toler
authors.forename: Daniel
authors.initials: D
authors.lastname: Yohannes
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Lippiello
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D019459:Urothelium / Q000378:metabolism
chemical_list: D018680:Cholinergic Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic