Experimental studies of urinary incontinence. Effect of tiropramide on the urinary stage and evacuation

Tiropramide, a tyrosine derivative, has an antispasmodic effect on the gastrointestinal smooth muscles and it is suggested that the effect is mediated by cAMP. Therefore, we studied the effects of tiropramide on the lower urinary tract smooth muscle functions. In animal experiments, the effects of tiropramide on vesicourethral smooth muscle contraction were investigated and cAMP and cGMP levels following tiropramide administration were measured in the vesicourethral and gastrointestinal smooth muscles. In clinical trials, five healthy volunteers and five patients with neurogenic bladder dysfunction were treated orally with tiropramide 300 mg a day for two weeks and examined for urodynamic parameters before and after tiropramide treatment. Tiropramide significantly inhibited contraction of the vesicourethral smooth muscle and the inhibitory effect upon the bladder was remarkable particularly at the lower concentrations. Tiropramide remarkably increased cAMP level but it had no effect on cGMP level in the bladder at the lower concentrations. Tiropramide at the lower concentrations did not affect cAMP and cGMP levels in the smooth muscles of the urethra, stomach and intestines. In the patients with neurogenic bladder dysfunction treated with tiropramide orally, the urine volume at first desire to void and maximum bladder capacity increased significantly, but the volume of residual urine did not significantly increase. In the healthy volunteers, there were no significant changes in urodynamic parameters. These findings indicate that tiropramide relaxes the urinary bladder smooth muscle via cAMP to increase the urinary bladder capacity.