Resiniferatoxin And Botulinum Toxin Type A For Treatment Of Lower Urinary Tract Symptoms

Main Category: Urology / Nephrology
Also Included In: Clinical Trials / Drug Trials
Article Date: 13 Jan 2008 - 0:00 PDT

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UroToday.com- Resiniferatoxin (RTX) and botulinum toxin type A (BTX-A) have drawn increasing attention in recent years as potential treatments for lower urinary tract symptoms (luts), including overactive bladder (OAB). RTX acts by desensitizing the transient receptor potential vanilloid type 1 (TRPV1) a non-specific Ca2+ channel previously known as vanilloid receptor. BTX-A is used in purified form as a medication for disorders involving involuntary muscle contractions including blepharospasm and strabismus. It acts by inhibiting the fusion of neurotransmitter-containing synaptic vesicles with the neuronal membrane an event essential for the release of neurotransmitters. It also reduces the release of glutamate and substance P from sensory neurons thus reducing the transmission of sensory input by these cells. Both drugs have been used in patients with bladder pain syndrome / interstitial cystitis. Cruz and Dinis from Porto, Portugal present an interesting review of the use of these compounds for the treatment of urinary disorders.

A role for intravesical RTX and BTX-A in the treatment of inflammatory bladder pain and frequency is strongly supported from data collected from animal models of chronic cystitis. Studies of RTX in humans for bladder pain syndrome are conflicting. A small randomized and placebo controlled trial of 18 patients showed good results at one month with no significant benefit at 3 months. A large pharmaceutical trial with 163 patients and several different doses of RTX compared to placebo showed no efficacy or even a potential signal of efficacy. For BTX-A, the results have also been contradictory in clinical trials. Not only is efficacy in question, but it carries risks of urinary retention that are not insignificant.

The authors conclude that RTX faces hurdles because of difficulties preparing stable preparations for easy bladder instillation. BTX faces the problem of the need for intradetrusor injection rather than intravesical administration. While clinical data for overactive bladder are promising for BTX-A, data for bladder pain syndrome for both compounds has been disappointing. Their use for interstial cystitis should be limited to controlled clinical trials.

Cruz F, Dinis P

Neurourol Urodyn. 26(s6):920-927, October 2007
DOI: 10.1002/nau.20479

Reported by UroToday.com Contributing Editor Philip Hanno M.D

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