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Updated: May 18, 2026
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Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
JTS-653 blocks afferent nerve firing and attenuates bladder overactivity without affecting normal voiding function.
Yoshihiro Kitagawa1, Masashi Wada, Tomokazu Kanehisa
1Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Osaka, Japan. yoshihiro.kitagawa@jt.com
The Journal of Urology
|September 25, 2012
Summary
A novel TRPV1 antagonist, JTS-653, effectively treats bladder overactivity by targeting afferent nerve activation. This compound shows promise for overactive bladder treatment, distinct from existing antimuscarinic drugs.
Area of Science:
- Urology
- Neuroscience
- Pharmacology
Background:
- Bladder overactivity is a condition characterized by urinary urgency and frequency.
- Transient Receptor Potential Vanilloid 1 (TRPV1) channels are implicated in sensory nerve function and pain signaling.
- The role of TRPV1 in bladder overactivity requires further elucidation.
Purpose of the Study:
- To investigate the role of TRPV1 in bladder overactivity.
- To evaluate the efficacy of a selective TRPV1 antagonist, JTS-653, in preclinical models of bladder overactivity.
- To assess the effects of JTS-653 on afferent nerve firing and urodynamic parameters.
Main Methods:
- In vivo studies in anesthetized rats to measure pelvic nerve discharge and intravesical pressure responses to capsaicin.
- Cystometry in conscious rats to evaluate urodynamic parameters (intercontraction interval, voided volume, maximal voiding pressure) in models of resiniferatoxin- or acetic acid-induced bladder overactivity.
- In vitro studies using bladder muscle strips to assess the effects of JTS-653 on carbachol-induced contractions.
Main Results:
- JTS-653 significantly suppressed capsaicin-induced increases in nerve discharge and intravesical pressure.
- In models of induced bladder overactivity, JTS-653 increased intercontraction interval and voided volume without affecting maximal voiding pressure.
- JTS-653 did not impact normal bladder activity or carbachol-induced bladder muscle contractions, and its effects differed from the antimuscarinic agent propiverine.
Conclusions:
- TRPV1 activation by afferent nerves plays a significant role in bladder overactivity.
- TRPV1 is not associated with normal voiding function.
- TRPV1 antagonists like JTS-653 represent a potential therapeutic strategy for bladder overactivity with a distinct mechanism from antimuscarinic agents.
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