Elzayat Ehab, Khaled Sabri, Kashiwabara Takeshi, Elhilali Mostafa, Corcos Jacques
Department of Urology, McGill University, Montreal, Quebec, Canada.
Neurourol Urodyn. 2006;25(7):808-14. doi: 10.1002/nau.20284.
To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model.
Forty-eight female Sprague-Dawley rats were used in this study. Six animals served as normal controls (without spinal cord transaction (ST)), while 42 rats underwent ST at the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was performed in six randomly chosen animals to ensure the development of neurogenic detrusor overactivity. The remaining 36 rats were divided into three equal groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537 0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and treatment group was further divided into two sub-groups (n = 6), with CMG at 3 and 4 weeks after ST, respectively.
Two weeks after ST, all "vehicle control" rats developed detrusor overactivity with a mean frequency of 0.96 and 1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2-week treatment, respectively. Neurogenic detrusor overactivity disappeared from 50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor overactivity vanished from 67% of the animals with even further reduction in the frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared from only one animal with a non-significant decline in frequency. Fifty percent of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no detrusor overactivity.
WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.
在慢性截瘫大鼠模型中测试WAY-133537治疗膀胱过度活动症（OAB）的疗效。
本研究使用了48只雌性Sprague-Dawley大鼠。6只动物作为正常对照（无脊髓横断（ST）），而42只大鼠在第10胸椎处进行了脊髓横断。脊髓横断后两周，对随机选取的6只动物进行膀胱压力容积测定（CMG），以确保神经源性逼尿肌过度活动的发展。其余36只大鼠分为三组，每组12只，12只接受赋形剂作为“截瘫对照”，12只接受0.3 mg/kg的WAY-133537，12只接受3 mg/kg的WAY-133537。每个“截瘫对照”组和治疗组进一步分为两个亚组（n = 6），分别在脊髓横断后3周和4周进行膀胱压力容积测定。
脊髓横断后两周，所有“赋形剂对照”大鼠均出现逼尿肌过度活动，治疗1周和2周时平均收缩频率分别为0.96次/分钟和1.48次/分钟，幅度分别为22.96 cm H₂O和31.22 cm H₂O。接受0.3 mg/kg WAY-133537治疗1周的大鼠中，50%的神经源性逼尿肌过度活动消失，频率降至0.41次/分钟。治疗2周后，67%的动物逼尿肌过度活动消失，逼尿肌过度活动频率进一步降低（0.22次/分钟，P < 0.01）。接受3 mg/kg药物治疗1周的大鼠中，只有1只动物的逼尿肌过度活动消失，频率下降不显著。给予3 mg/kg/天WAY-133537治疗2周的大鼠中，50%未表现出逼尿肌过度活动。
WAY-133537在不降低排尿压力的情况下，可有效增加大鼠脊髓横断后的膀胱容量并降低自发性膀胱收缩频率。
