Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
School of Rehabilitation Sciences, Health Sciences University of Hokkaido, Tobetsu, Japan.
Neurourol Urodyn. 2018 Nov;37(8):2382-2388. doi: 10.1002/nau.23586. Epub 2018 Apr 6.
The serotonin (5-HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity. However, it is unclear whether this selective 5-HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD).
Normal female rats and rats with stress incontinence induced by VD were tested. We evaluated the effect of a single dose of lorcaserin (0.03, 0.3, or 0.9 mg/kg with cumulative administration) on the urethral pressure amplitude during electrical stimulation (A-URE) and on the urethral baseline pressure (UBP). The manual compression-induced leak point pressure (LPP) was also measured.
In VD rats, a single intravenous injection of lorcaserin (0.3 and 0.9 mg/kg) significantly increased both A-URE and LPP compared to saline (P < 0.05). In normal rats, intravenous lorcaserin (0.3 and 0.9 mg/kg) also significantly increased A-URE and LPP compared to saline (P < 0.05). The changes of A-URE and LPP, which are parameters of active urethral closure, were significantly larger in normal rats than in VD rats.
We showed that lorcaserin can activate the external urethral sphincter and pelvic floor muscles, suggesting an influence on active closure mechanisms. 5-HT2c receptors agonists may have dual effects in patients with SUI, not only by reducing obesity but also by enhancing active urethral closure.
已知 5-羟色胺（5-HT2c）受体参与压力性尿失禁模型中的尿道闭合机制。Lorcaserin（Belviq®）已获得美国食品和药物管理局批准用于治疗肥胖症。然而，尚不清楚这种选择性 5-HT2c 受体激动剂是否会增强压力性尿失禁（SUI）模型中的尿道闭合。因此，我们研究了 lorcaserin 是否可以增强阴道扩张（VD）诱导的女性大鼠的尿道闭合。
测试了正常雌性大鼠和压力性尿失禁大鼠。我们评估了单次给予 lorcaserin（0.03、0.3 或 0.9mg/kg 累积给药）对电刺激时尿道压力幅度（A-URE）和尿道基础压（UBP）的影响。还测量了手动压迫诱导的漏尿点压（LPP）。
在 VD 大鼠中，单次静脉注射 lorcaserin（0.3 和 0.9mg/kg）与生理盐水相比，均显著增加 A-URE 和 LPP（P<0.05）。在正常大鼠中，静脉注射 lorcaserin（0.3 和 0.9mg/kg）也显著增加 A-URE 和 LPP 与生理盐水相比（P<0.05）。主动尿道闭合的参数 A-URE 和 LPP 的变化在正常大鼠中明显大于 VD 大鼠。
我们表明 lorcaserin 可以激活尿道外括约肌和盆底肌，这表明对主动闭合机制有影响。5-HT2c 受体激动剂在 SUI 患者中可能具有双重作用，不仅可以减轻肥胖，还可以增强主动尿道闭合。
