title: Effects of ritobegron (KUC-7483), a novel β3-adrenoceptor agonist, on both rat bladder function following partial bladder outlet obstruction and on rat salivary secretion: a comparison with the effects of tolterodine.
abstract: The objective of this study was to investigate the effects of the β3-adrenoceptor (AR) agonist ritobegron on rat bladder function following partial bladder outlet obstruction and on rat salivary secretion. In addition, the effects of ritobegron were compared with those of the anti-muscarinic agent tolterodine. After a 6-week partial bladder outlet obstruction (BOO), drug effects on bladder functions were evaluated using cystometrography. Effects on carbachol (CCh)-induced salivary secretion were evaluated in urethane-anesthetized rats. Ritobegron significantly decreased the frequency of non-voiding contractions (NVC), while both ritobegron and tolterodine each significantly decreased the amplitude of NVC. Ritobegron had no effect on either the micturition pressure (MP) or the residual volume (RV). In contrast, tolterodine dose-dependently decreased MP and increased RV. Ritobegron had no effect on CCh-induced salivary secretion, whereas tolterodine dose-dependently decreased it. Ritobegron decreased both the frequency and amplitude of NVC, which is similar to its effect on the contractions associated with detrusor overactivity (DO) in patients with an overactive bladder (OAB), without affecting MP, RV, or CCh-induced salivary secretion. Although tolterodine reduced the amplitude of NVC, it also markedly increased RV and significantly inhibited CCh-induced salivary secretion. These results suggest that use of ritobegron, a β3-AR agonist, is unlikely to lead to the residual urine and dry mouth symptoms that are associated with anti-muscarinic drugs, and that ritobegron may hold promise as a safe and effective agent for OAB treatment.
authors.affiliation: Kissei Pharmaceutical Co., Ltd., Japan. itaru_maruyama@pharm.kissei.co.jp
authors.forename: Itaru
authors.initials: I
authors.lastname: Maruyama
authors.forename: Saori
authors.initials: S
authors.lastname: Yonekubo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tatemichi
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Maruyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hoyano
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusama
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003408:Cresols / Q000494:pharmacology*; D005260:Female; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism*; D013997:Time Factors; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000503:physiopathology*; D010136:p-Hydroxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000085:Acetates; D058667:Adrenergic beta-3 Receptor Agonists; D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; D010136:p-Hydroxyamphetamine; C576374:ritobegron