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MP94-14: Urodynamic evaluation of DA-8010 in conscious rats with partial bladder outlet obstruction

Tuesday, May 16
7:00 AM - 9:00 AM
Location: BCEC: Room 253AB

Presentation Authors: Min Soo Choo*, Hwaseong, Korea, Republic of, Jun-Hwan Moon, Hyung Keun Lee, Min Jung Lee, Yongin, Korea, Republic of, Seong Ho Lee, Jun Hyun Han, Hwaseong, Korea, Republic of, Sung Hak Choi, Yongin, Korea, Republic of

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.

Source Of Funding: none

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