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Modulation of Bladder Afferent Activity by Propiverine and its Active Metabolites (M-1 and M-2) in Rats

Authors


Naoki Yoshimura, MD, PhD, Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. Tel: 412-692-4137; Fax: 412-692-4380. Email: nyos@pitt.edu

Abstract

Objectives: To evaluate the effects of propiverine and its active metabolites (M-1 and M-2) on bladder function through modulation of afferent activity in rats.

Methods: Cystometry was performed in urethane anesthetized female rats. We examined the effects of intravesical administration of propiverine, M-1 and M-2 on bladder overactivity induced by oxotremorine-M (Oxo-M; non-selective mAChR agonist).

Results: Intravesical administration of Oxo-M (200 µM) elicited bladder overactivity as evidenced by decreased intercontraction interval (ICI) and pressure threshold (PT) without changing maximum voiding pressure or baseline pressure. These effects were blocked by intravesical administration of propiverine (30 µM) or M-2 (300 µM). Intravesical administration of M-1 (30 µM) alone increased ICI and PT, but did not prevent Oxo-M-induced decreases in ICI and PT.

Conclusion: These results suggest that propiverine and M-2 have anticholinergic effects on bladder afferent activity and that M-1 has an inhibitory effect through the mechanism other than muscarinic receptor modulation. Thus, clinical benefits of propiverine in patients with overactive bladder could be mediated by multiple actions of propiverine and its active metabolites.

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