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

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概要

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• 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.

著者

• Tatemichi Satoshi

  Kissei Pharmaceutical Co., Ltd., Japan

• Maruyama Itaru

  Kissei Pharmaceutical Co., Ltd., Japan

• Yonekubo Saori

  Kissei Pharmaceutical Co., Ltd., Japan

• Maruyama Kazuyasu

  Kissei Pharmaceutical Co., Ltd., Japan

• Hoyano Yuji

  Kissei Pharmaceutical Co., Ltd., Japan

• Yamazaki Yoshinobu

  Kissei Pharmaceutical Co., Ltd., Japan

• Kusama Hiroshi

  Kissei Pharmaceutical Co., Ltd., Japan

• KUSAMA Hiroshi

  Kissei Pharmaceutical Co., Ltd.

• TATEMICHI Satoshi

  Kissei Pharmaceutical Co., Ltd.

関連論文

• 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
• Effects of ritobegron (KUC-7483), a novel β_3-adrenoceptor agonist, on both rat bladder function following partial bladder outlet obstruction and on rat salivary secretion : a comparison with the effects of tolterodine

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