Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1, Kashiwabara, Hotaka, Azumino-city, Nagano, 399-8304, Japan.
Watarase Research Center, Kyorin Pharmaceutical Co., Ltd, 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan.
Eur J Pharmacol. 2020 Jul 5;878:173096. doi: 10.1016/j.ejphar.2020.173096. Epub 2020 Apr 4.
Urgency is regarded as a core symptom of overactive bladder (OAB) and may correspond to detrusor overactivity (DO). One of the causes of OAB in men is bladder outlet obstruction (BOO) associated with benign prostatic hyperplasia (BPH). Vibegron is a novel selective β-adrenoceptor agonist recently approved for the treatment of OAB. However, in OAB patients with BPH (BPH/OAB), the effects of vibegron on storage functions, especially DO and voiding functions have not been fully investigated. In this study, we evaluated the effects of a single administration of vibegron on storage function (particularly focusing on non-voiding contractions [NVC] considered a surrogate marker for DO) and voiding functions, using a rat model of partial BOO as a model for BPH/OAB. Furthermore, the utility of vibegron in combination with imidafenacin (an antimuscarinic) or silodosin (an α-adrenoceptor blocker) was evaluated. Six weeks after establishment of BOO, the frequency and amplitude of NVC, evaluated by cystometrography, increased. Vibegron inhibited the frequency of NVC without affecting voiding function (micturition pressure, residual volume, and voiding efficiency). Imidafenacin and silodosin also inhibited the frequency of NVC; however, the inhibitory effects of vibegron were stronger than those of imidafenacin or silodosin. The combination of vibegron with imidafenacin or silodosin additively inhibited the frequency of NVC without worsening the voiding function. These results suggest the possibility that vibegron is effective as a single agent for the amelioration of storage symptoms in BPH/OAB patients and is useful in combination with either antimuscarinics or α-adrenoceptor blockers.
急迫性被认为是膀胱过度活动症（OAB）的核心症状，可能与逼尿肌过度活动（DO）相对应。男性 OAB 的一个原因是与良性前列腺增生（BPH）相关的膀胱出口梗阻（BOO）。Vibegron 是一种新型选择性β-肾上腺素受体激动剂，最近被批准用于治疗 OAB。然而，在 BPH 合并 OAB（BPH/OAB）患者中，Vibegron 对储存功能（特别是逼尿肌过度活动的替代标志物非排尿收缩（NVC））和排尿功能的影响尚未得到充分研究。在这项研究中，我们使用部分 BOO 大鼠模型作为 BPH/OAB 模型，评估了 Vibegron 单次给药对储存功能（特别是聚焦于被认为是逼尿肌过度活动替代标志物的非排尿收缩（NVC））和排尿功能的影响。此外，还评估了 Vibegron 与伊米沙芬（一种抗毒蕈碱药物）或西洛多辛（一种α-肾上腺素受体阻滞剂）联合应用的效果。BOO 建立 6 周后，通过尿动力学检查评估的 NVC 频率和幅度增加。Vibegron 抑制 NVC 的频率而不影响排尿功能（排尿压力、残余尿量和排尿效率）。伊米沙芬和西洛多辛也抑制了 NVC 的频率；然而，Vibegron 的抑制作用强于伊米沙芬或西洛多辛。Vibegron 与伊米沙芬或西洛多辛联合应用可协同抑制 NVC 的频率，而不会加重排尿功能。这些结果表明，Vibegron 作为 BPH/OAB 患者改善储存症状的单一药物可能有效，并且与抗毒蕈碱药物或α-肾上腺素受体阻滞剂联合使用有用。
