Excitatory effect of acotiamide on rat and human bladder: Implications for underactive bladder treatment

Abstract

Objective: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect in bladder to help explain the reported meaningful reduction of post-void residual urine volume (PVR) in detrusor underactivity (DU) patients after thrice daily oral intake of acotiamide 100 mg for 2 weeks.Methods-Effect of acotiamide [1-16μM] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5s with 5ms pulse trains of 10V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1-32Hz) and repeat 10Hz stimulation at 60s interval. Effect of acotiamide 2μM on spontaneous and carbachol evoked contractions was also assessed.Results-Acotiamide 2μM significantly enhanced the Atropine and Tetrodotoxin (TTX)sensitive EFS evoked contractions of rat and human bladder at 8-32Hz (Two-way ANOVA followed Sidak's multiple comparison; *p<0.01) and on repeat 10Hz stimulation (Paired Student's t test;*p<0.05), while producing a modest effect on the spontaneous contractions and a negligible effect on the carbachol evoked contractions.Conclusions-Enhancement of TTX-sensitive evoked contractions of rat and human bladder by acotiamide is consistent with the enhancement of excitatory neuro-effector transmission mainly through prejunctional mechanisms. Findings highlights immense therapeutic potential of antimuscarinics with low M3 receptor affinity like acotiamide in Underactive bladder (UAB)/DU treatment.

Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder

“…Up to now, various of treatments were attempted to attenuate symptoms and improve bladder functions of UAB [ 9 – 11 ]. Stem cell therapy has attracted widespread attention as an effective approach to the regeneration of tissues.…”

Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder

“…Up to now, various of treatments were attempted to attenuate symptoms and improve bladder functions of UAB [9][10][11]. Stem cell therapy has attracted widespread attention as an effective approach to the regeneration of tissues.…”