Immuno-Modulatory imide Drugs (IMiDs) inhibit human bladder smooth muscle contraction: A novel drug class in LUTS?

Introduction & Objectives

Medical treatment in lower urinary tract symptoms (LUTS) includes reduction of prostate and detrusor smooth muscle tone. Due to an unfavourable balance between side effects and limited efficacy, current medications cause high rates of patient non-compliance and treatment discontinuation. Recently, we could show that IMiDs (thalidomide, lenalidomide and pomalidomide) inhibit prostate smooth muscle contraction, modulate cytoskeletal actin organization, and reduce prostate stromal cell growth, without causing cytotoxic side effects. Here, we addressed effects of IMiDs on cholinergic and non-cholinergic contractions of human detrusor smooth muscle.

Materials & Methods

Detrusor wall tissues were obtained from patients undergoing radical cystectomy for bladder cancer (n=83 patients). Contractility of detrusor strips was then assessed in an organ bath.

Results

IMiDs ([1] thalidomide 100µM, [2] lenalidomide 20µM, and [3] pomalidomide 5µM) inhibited cholinergic contractions at a varying degree, by 27-39% and 30-43% for concentrations of 0.1-1000µM carbachol and methacholine, respectively. Non-cholinergic contractions were inhibited by 44-50% and 37-53% for thromboxane A2 analogue U46619, and endothelin-1, respectively. While thalidomide and lenalidomide had no or only marginal effect on EFS-induced neurogenic contractions, pomalidomide inhibited EFS-induced contractions by 35%.

Conclusions

Together with our previous data on prostate smooth muscle contraction, the observed varying susceptibility to cholinergic, non-cholinergic, and neurogenic contractions suggests specificity and differences in IMiDs on smooth muscle contractility in the lower urinary tract, and a possible novel drug class in LUTS treatment.