title: Are antimuscarinic drugs effective against urinary frequency mediated by atropine-resistant contractions?
abstract: In the disease states of urinary frequency and urgency, atropine-resistant contractions are known to be involved, in addition to contractions mediated by cholinergic nerves. This study was undertaken to investigate the mechanism underlying the development of atropine-resistant contractions using the representative antimuscarinic drugs solifenacin and tolterodine and also propiverine that has Ca(2+) channel-antagonizing activity in addition to antimuscarinic activity. Rat models of urinary frequency were established by intravesical infusion of acetylcholine (ACh) (cholinergic nerve-mediated urinary frequency model), acetic acid (AcOH) [non-adrenergic non-cholinergic nerve (NANC)-mediated urinary frequency model], or CaCl(2) (atropine-resistant contractions-mediated urinary frequency model). Cystometrograms were obtained to measure the micturition parameters following oral administration of the aforementioned drugs. Propiverine increased the micturition weight in all the urinary frequency models. Solifenacin and tolterodine increased the micturition weight in the ACh-induced urinary frequency model but neither had any effect in the AcOH- or CaCl(2)-induced urinary frequency models. While antimuscarinic drugs are, in general, effective for the control of urinary frequency and incontinence, use of drugs possessing inhibitory effects on contractions mediated by cholinergic as well as NANC nerve transmission or Ca(2+) influx into smooth muscles is recommended for management of the symptoms in disease states in which atropine-resistant contractions, such as Ca(2+)- and capsaicin-sensitive sensory nerves, are involved.
authors.affiliation: Department of Applied Pharmacology, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: Fukumitsu
authors.initials: F
authors.lastname: Sakakibara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
authors.forename: Masato
authors.initials: M
authors.lastname: Nanri
mesh_terms: D000818:Animals; D001285:Atropine / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000188:drug therapy; D014554:Urination / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018727:Muscarinic Antagonists; D050916:TRPV Cation Channels; D001285:Atropine