A novel pyrrole derivative, NS-8, suppresses the rat micturition reflex by inhibiting afferent pelvic nerve activity
Article first published online: 24 NOV 2003
Volume 92, Issue 9, pages 1031–1036, December 2003
How to Cite
Tanaka, M., Sasaki, Y., Kimura, Y., Fukui, T., Hamada, K. and Ukai, Y. (2003), A novel pyrrole derivative, NS-8, suppresses the rat micturition reflex by inhibiting afferent pelvic nerve activity. BJU International, 92: 1031–1036. doi: 10.1111/j.1464-410X.2003.04512.x
- Issue published online: 24 NOV 2003
- Article first published online: 24 NOV 2003
- Accepted for publication 16 July 2003
- bladder capacity;
- overactive bladder
To investigate the suppressive effect of a newly synthesized compound, 2-amino-3-cyano-5-(2-fluorophenyl)-4-methylpyrrole (NS-8), on micturition, and its mode and sites of action in rats.
MATERIALS AND METHODS
Female rats were anaesthetized with urethane, and isovolumetric bladder contractions and cystometrograms recorded. The pelvic afferent discharges from the bladder were also monitored.
In the cystometric study, NS-8 increased the bladder capacity without affecting the maximum bladder contraction pressure, an effect unlike that of currently used anticholinergic drugs for the overactive bladder, which commonly decrease the maximum bladder contraction pressure. Intravesical and intravenous injection of NS-8 inhibited isovolumetric bladder contractions in a dose-dependent manner without affecting their amplitude, whereas intracerebroventricular injection with NS-8 had no such effect. During the urine storage phase of the cystometrogram, NS-8 decreased the discharge rate of the afferent pelvic nerve from the bladder, in association with a decrease in the increase in intravesical pressure.
NS-8 suppressed the micturition reflex by decreasing afferent pelvic nerve activity. Activation of calcium-sensitive potassium channel of the bladder may be responsible for such an effect. This agent has the potential to treat patients with urinary frequency and incontinence.