Abstract
BackgroundDA-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.MethodsStudy 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.ResultsThere 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.ConclusionsOral 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.
Highlights
DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence
Increases in the contraction interval were observed in the other DA-8010 groups, but these changes were not statistically significant
M3 muscarinic receptors are well known to play a predominant role in mediating bladder muscle, both the M2 and M3 muscarinic receptor subtypes are located on bladder smooth muscle [15, 16]
Summary
DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. Overactive bladder (OAB), a syndrome characterized by urgency (with or without urge incontinence), frequency, and nocturia, is common in both men and women and increases in prevalence with age [1]. Treatment with antimuscarinic and behavioral therapy is one of the first-line management methods for patients with OAB. These drugs inhibit the binding of acetylcholine to the muscarinic receptor in the detrusor muscle and urothelium during detrusor contraction. While anticholinergics can be effective in OAB, they carry risk of various complications, such as dry mouth, constipation, acute urinary retention, and visual disturbance. There is a need for new OAB treatments that demonstrate high efficacy and fewer side effects
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