title: Effect of mirabegron, a novel β3-adrenoceptor agonist, on bladder function during storage phase in rats.
abstract: Mirabegron, a selective β(3)-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage.
authors.affiliation: Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. toshiki.hatanaka@astellas.com
authors.forename: Toshiki
authors.initials: T
authors.lastname: Hatanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Ukai
authors.forename: Mai
authors.initials: M
authors.lastname: Watanabe
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Someya
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ohtake
authors.forename: Masanori
authors.initials: M
authors.lastname: Suzuki
authors.forename: Koji
authors.initials: K
authors.lastname: Ueshima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sato
authors.forename: Seiji
authors.initials: S
authors.lastname: Kaku
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D003408:Cresols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008333:Mandelic Acids / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010665:Phenylpropanolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy*
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D001559:Benzhydryl Compounds; D003408:Cresols; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D013844:Thiazoles; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin; C520025:mirabegron