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

LIFE SCIENCES

卷:258

Article

Singh, Nishant¹  Mizoguchi, Shinsuke¹  Suzuki, Takahisa¹  Zabbarova, Irina²  Ikeda, Youko²  Kanai, Anthony²  Chermansky, Christopher¹  Yoshimura, Naoki¹  Tyagi, Pradeep¹ 

[1] Univ Pittsburgh, Dept Urol, E313 Montefiore Hosp,3459 Fifth Ave, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA

关键词: Underactive bladder;    Acotiamide;    Antimuscarinic;    Nerve evoked;    Bethanechol;   

DOI  :  10.1016/j.lfs.2020.118179

来源: Elsevier

【 摘 要 】

Objective: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect on 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 [1-16 mu M] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5 s with 5 ms pulse trains of 10 V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1-32 Hz) and repeat 10 Hz stimulation at 60s interval. Effect of acotiamide 2 mu M on spontaneous and carbachol evoked contractions was also assessed. Results: Acotiamide 2 mu M significantly enhanced the Atropine and Tetrodotoxin (ITX)-sensitive EFS evoked contractions of rat and human bladder at 8-32 Hz (Two-way ANOVA followed Sidak's multiple comparison; *p < 0.01) and on repeat 10 Hz 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 highlight immense therapeutic potential of antimuscarinics with low M3 receptor affinity like acotiamide in Underactive bladder (UAB)/DU treatment.

【 授权许可】

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