The effects of oral administration of the novel muscarinic receptor antagonist DA-8010 on overactive bladder in rat with bladder outlet obstruction.

DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. The aims of this study were to investigate the effects of DA-8010 on OAB in a rat model.

Study animals were divided into the following five groups of seven animals each: a sham-operated control group, a control group with partial bladder outlet obstruction (BOO) (OAB group), and three DA-8010 (doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day, respectively) with partial BOO groups. Oral administration of the drugs was continued for 14 days after 2 weeks of partial BOO. After 4 weeks of partial BOO, cystometrography was performed in all groups. Additionally, pro-inflammatory cytokines, Rho-kinases, and histology of the bladder were analyzed.

There was a significant increase in the contraction interval and a decrease in contraction pressure in the 3 mg/kg/day DA-8010 group versus those in the OAB group. Rho kinase was also significantly decreased in the DA-8010 3 mg/kg/day dosage treatment group. The increased ratio of collagen to smooth muscle after partial BOO was significantly attenuated in the DA-8010 3 mg/kg/day dosage group.

Oral administration of DA-8010 at 3 mg/kg/day improved findings in an OAB rat model induced by partial BOO. Our results suggest that the novel muscarinic receptor antagonist DA-8010 may be a promising drug for treating patients with OAB.

BMC urology. 2020 Apr 17*** epublish ***

Jin Bong Choi, Seung Hwan Jeon, Eun Bi Kwon, Woong Jin Bae, Hyuk Jin Cho, U-Syn Ha, Sung-Hoo Hong, Ji Youl Lee, Sae Woong Kim

Department of Urology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Korea Bio Medical Science Institute, Seoul, Republic of Korea., Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea and Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea., Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea and Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 06591, Seoul, Republic of Korea. .

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