Abstract
PURPOSE: To investigate the effectiveness of acotiamide on lower urinary tract dysfunction by using a rat model of neurogenic underactive bladder induced through pelvic nerve crush (PNC) injury. METHODS: Bilateral PNC injuries were performed on 8-week-old female Sprague-Dawley rats (PNC group); the sham surgery group was used as control (control group). Two weeks after surgery, awake cystometrography (CMG) was performed, and acotiamide (10 or 100 mg/kg) was subcutaneously administered to the control and PNC groups. Subsequently, CMG parameter values obtained before and after treatment were compared. RESULTS: In baseline CMG, compared to control group, PNC group revealed statistically significant elevations in the intercontraction intervals (ICIs), number of nonvoiding contractions, baseline pressure, threshold pressure, bladder capacity, voided volumes, and postvoid residual. However, contraction amplitudes and voiding efficiency were significantly decreased. In the control group, compared with the baseline values, 10-mg/kg acotiamide resulted in statistically significant elevations in contraction amplitudes. Treatment with 100-mg/kg acotiamide led to statistically significant elevations in contraction amplitudes and decreases in ICI and bladder volume. In the PNC group, there were no statistically significant changes noted in CMG parameters after treatment with 10-mg/kg acotiamide (n=6). Compared with the baseline values, the administration of 100-mg/kg acotiamide significantly decreased ICI (1,025±186 seconds vs. 578±161 seconds; P=0.012), bladder capacity (1,841±323 µL vs. 871±174 µL, respectively; P=0.0059) and postvoid residual (223±46 µL vs. 44±22 µL, respectively; P=0.023), and increased contraction amplitudes (22.09±1.76 cm H2O vs. 43.84±6.87 cm H2O, respectively; P=0.012) and voiding efficiency (0.87±0.02 vs. 0.94±0.03, respectively; P=0.029). CONCLUSION: Acotiamide showed effectiveness in the treatment of underactive bladder, possibly through activation of bladder afferent and detrusor activities.