Login to Access Video or Poster Abstract: MP94-14
Sources of Funding: none

Introduction

DA-8010 is a novel, bladder-selective muscarinic receptor 3 antagonist being developed for the treatment of overactive bladder (OAB). The objectives of this study were to investigate the urodynamic effects of DA-8010 on detrusor overactivity (DO) in awake rats with partial bladder outlet obstruction (pBOO) and to compare its effect with that of a currently used antimuscarinic agent, solifenacin.

Methods

A total of 40 female Sprague-Dawley rats were subjected to sham operated controls (n=8) and pBOO. DO was induced by partial urethral ligation for 5 weeks. Rats with DO were divided randomly into 4 groups, treated with DA-8010 0.03 mg/kg, DA-8010 0.1 mg/kg, solifenacin 0.2 mg/kg, and solifenacin 1 mg/kg. Cystometrograms were obtained before and after intravenous administration of test compounds in unanesthetized, unrestrained rats in metabolic cages. After completion of the investigation, the bladder was isolated and weighted.

Results

Results of 37 rats were analyzed. Compared with sham controls, pBOO animals induced DO including shorter micturition intervals, smaller voided volume and reduced bladder capacity. After the administration of DA-8010, DO rats significantly showed longer micturition intervals, larger micturition volume and bladder capacity. In particular, there were no significant differences in residual volume. DA-8010 at 0.1 mg/kg also decreased the peak micturition pressure and basal pressure, whereas a dose of 0.03 mg/kg did not. Solifenacin increased the micturition interval, but did not affect micturition volume. At the higher dose, solifenacin significantly increased the residual volume.

Conclusions

DA-8010, a novel antimuscarinic agent exerts beneficial effects on the DO induced by pBOO in awake rats, demonstrating that DA-8010 increased both micturition intervals and micturition volume. Furthermore, whereas solifenacin exhibited increasing residual volume in rats with pBOO, DA-8010 did not affect it. These findings suggest that DA-8010 may be a urodynamically effective and safe agent for treatment of OAB and DO.

Funding

none