Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats

Abstract

Aims: 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). Methods: 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. Results: 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. Conclusions: 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.