Intravesical Capsaicin Versus Resiniferatoxin In Patients With Detrusor Hyperreflexia: A Prospective Randomized Study

Abstract

Purpose: Capsaicin and resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) administered intravesically are attractive options for treating detrusor hyperreflexia. Because the 2 agents differ in chemical structure and relative potency, possible differences in their clinical and urodynamic effects were investigated in this prospective comparative study.Materials and Methods: A group of 24 spinal cord injured patients with refractory detrusor hyperreflexia were randomly assigned to receive a single dose of 2 mM. capsaicin in 30 ml. ethanol plus 70 ml. 0.9% sodium chloride or 100 nM. resiniferatoxin in 100 ml. 0.9% sodium chloride. Dwell time was 40 minutes with urodynamic monitoring. Urodynamics were performed at baseline before treatment, and after followups of 30 and 60 days. The frequency of daily catheterizations, incontinence episodes and side effects was recorded.Results: There was no significant urodynamic or clinical improvement in the capsaicin arm at 30 and 60 days of followup. In the resiniferatoxin arm the mean uninhibited detrusor contraction threshold plus or minus standard deviation increased from 176 Ϯ 54 to 250 Ϯ 107 ml. at 30 days (p Ͻ0.05) and to 275 Ϯ 98 ml. at 60 days (p Ͻ0.01). Mean maximum bladder capacity increased from 196 Ϯ 75 to 365 Ϯ 113 ml. at 30 days (p Ͻ0.001) and to 357 Ϯ 101 ml. at 60 days (p Ͻ0.001). Daily catheterizations and incontinent episodes were significantly decreased at 30 and 60 days of followup. Autonomic dysreflexia, limb spasms, suprapubic discomfort and hematuria developed in most patients who received capsaicin but in none who received resiniferatoxin.Conclusions: Intravesical administration of resiniferatoxin is superior to that of capsaicin in terms of urodynamic results and clinical benefits in spinal cord injured patients and it does not cause the inflammatory side effects associated with capsaicin.

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC)

“…Another explanation may lie in the existence of subgroups of vanilloid receptors or C-fibres, for which CAP and RTX may have different affinities [21]. An interesting third alternative theory attributes the difference in initial irritation to ethanol, a solvent used in the vehicle to deliver CAP and RTX [22]. CAP is virtually insoluble in water and necessitates a considerable concentration of ethanol (30%) to solve into the required concentration.…”

“…The chosen concentrations were based on previous animal and human studies that showed that the desensitization effect of RTX was dose-dependent, and maximum efficacy was reached at 0.10 lM [21,22,24]. RTX concentration as high as 10 lM was used in patients with refractory detrusor hyperreflexia, with apparently few side effects [25].…”

Intérêt des thérapies intravésicales en neuro-urologie

“…La supériorité d'efficacité de la CPS par rapport à l'éthanol à 30 % [47] et un vecteur glucidique [48] et celle de la RTX par rapport à l'éthanol à 10 % sont éta-blies [41]. La répétition des instillations confère le même bénéfice [39][40][41][42][43][44][45][46][47][48]. Les patients grabataires, ceux présentant une forme avancée de SEP (EDSS > 7) ou un trouble sévère de la compliance vésicale répondent moins favorablement au traitement.…”

Synthesis and Biological Evaluation of Phorbol‐Resiniferatoxin (RTX) Hybrids

“…After 5 minutes, the reaction mixture was worked up by neutralisation with satd. NH 4 Cl and extraction with EtOAc. Washing with brine and drying (Na 2 SO 4 ) afforded a yellowish powder (660 mg), that, when analysed by 1 H NMR (300 MHz, CDCl 3 ) showed the presence only of 5b.…”

“…While undoubtedly providing new and exciting opportunities for discovery, none of these new ligands approaches RTX in terms of potency and pharmaceutical potential. RTX is currently in advanced clinical trials for treatment of diabetic neuropathy [3] and detrusor hyperreflexia, [4] and it is therefore surprising that its structure-activity relationships are still poorly understood. Furthermore, the recent discovery that the ultrapotent vanilloid activity of RTX can be reversed from agonist to an-and the structure-activity relationships for this class of vanilloid ligands were expanded.…”