Effect of the potassium channel opener WAY-133537 on the overactive bladder of spinalized rats.
OBJECTIVE
To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model.


METHODS
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.


RESULTS
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.


CONCLUSIONS
WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.
Elzayat
Ehab
E
Department of Urology, McGill University, Montreal, Quebec, Canada.
Khaled
Sabri
S
Kashiwabara
Takeshi
T
Elhilali
Mostafa
M
Corcos
Jacques
J
D000818:Animals; D002818:Cordotomy; D003503:Cyclobutanes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D010264:Paraplegia / Q000503:physiopathology*; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology
D003503:Cyclobutanes; D009570:Nitriles; D015221:Potassium Channels; C119323:WAY 133537