Resiniferatoxin for detrusor instability refractory to anticholinergics

Abstract

Purpose: We have evaluated the clinical and urodynamic effects of intravesical instillation of resiniferatoxin in patients with idiopathic detrusor instability refractory to anticholinergics.Materials and Methods: There were 30 women, median age 56 years old with detrusor instability for over 6 months and a history of anticholinergic use with no response or intolerable collateral effects. A 50 nM solution of resiniferatoxin was prepared for intravesical instillation. All patients were evaluated for urinary symptoms, as well as for urodynamic assessments before and 30 days after instillation. Tolerability was analyzed during the instillation.Results: A clinical improvement was observed in 30% of the patients with urinary urgency and in 33% of the patients with urge-incontinence. The mean maximum cystometric capacity before application was 303.9 ± 78.9 and after application 341 ± 84.6. No significant difference was observed (p = 0.585). The mean maximum amplitude of the contractions diminished from 47.86 ± 29.64 to 38.72 ± 30.77 (p = 0.002).Conclusions: Resiniferatoxin, in this concentration, proved to be useful in a small percentage of patients regarding clinical detrusor instability. Maximum amplitude of the involuntary contractions was significantly reduced and in 33% patients the involuntary contractions disappeared. Further studies with different concentrations are recommended.

Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin

“…The dichotomy between affinity and functional effects shown by some studies raises interesting questions about the functional relevance of residues identified as critical for RTX and capsaicin binding (Gavva et al 2004). It also underscores the importance and relevance of the action of RTX on TRPV1, especially in light of its usefulness for certain painful conditions (Helyes et al 2004) including urinary bladder hyper‐reflexia (Giannantoni et al 2004; Palma et al 2004).…”

“…This property might contribute to the lack of painful burning sensation with RTX, which is observed with capsaicin. Moreover, the RTX‐induced response is long lasting; therefore much lower concentrations of the drug than are being used currently (50–100 n m ) could potentially be used to achieve maximal activation of the receptor over a period of time in a therapeutically safe manner while avoiding potential side effects due to systemic absorption (Giannantoni et al 2004; Palma et al 2004). Current clinical trials for bladder hyper‐reflexia are being conducted to determine the most effective concentration of RTX and the duration of its application for optimum clinical benefits (Lazzeri et al 2004 a , b ; Payne et al 2005).…”

Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder

“…In contrast, the levels of urinary NGF of patients with idiopathic DO and neurogenic DO due to CVD were not significantly elevated. Palma et al 27 reported that intravesical RTX improved a small percentage of patients with female idiopathic DO. Yokoyama et al 28 reported that intravesical administration of lidocaine was less effective in patients with CVD than in patients with spinal cord diseases.…”

Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors

“…One can readily envisage that pharmacological intervention targeting urothelial TRPV1 is a valid option for the treatment of lower urinary tract diseases. However, although regimens for intravesical administration of capsaicin and RTX to desensitize afferent nerve fibres showed beneficial effects in clinical trials regarding neurogenic detrusor hyperreflexia, interstitial cystitis, and bladder pain, the instability of efficacy and the possible adverse effects have prevented further clinical evaluation [ [157] , [158] , [159] , [160] , [161] , [162] , [163] , [164] , [165] , [166] , [167] , [168] , [169] , [170] , [171] , [172] , [173] , [174] , [175] , [176] , [177] , [178] ]. XEN-D0501, a novel oral TRPV1 antagonist of high interest, has not been investigated in clinical trial for overactive bladder, and it is unclear whether this is associated with the undesirable increase in body temperature observed during safety evaluation [ 179 ].…”