Research Institute of Dong-A Pharmaceutical Company, Yong-in, Kyoung-gi, South Korea; College of Pharmacy, Ajou University, Yeongtong, Suwon, South Korea.
Int J Urol. 2014 Mar;21(3):325-9. doi: 10.1111/iju.12256. Epub 2013 Aug 22.
DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model.
Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg.
DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h.
Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation.
DA-8031 是一种高效、选择性的 5-羟色胺转运体抑制剂，用于治疗早泄。本研究旨在观察 DA-8031 对雄性大鼠性行为的影响。
通过雌性大鼠交配实验，研究了急性口服 10、30 或 100mg/kg DA-8031 对大鼠性行为的影响。在口服 30mg/kg DA-8031 后计算药代动力学参数。
DA-8031 治疗呈剂量依赖性增加射精潜伏期，并在 30 和 100mg/kg 剂量水平与载体组相比具有统计学意义（P<0.05）。此外，DA-8031 治疗呈剂量依赖性减少平均射精次数。在任何剂量下，后射精间隔、交配次数、插入次数或射精次数均无变化。在药代动力学研究中，口服后 0.38±0.14h 达峰血药浓度，半衰期为 1.79±0.32h。
DA-8031 治疗可延迟射精潜伏期，而不影响大鼠的起始交配行为或射精后间隔。此外，DA-8031 在大鼠口服后迅速吸收和消除。这些临床前发现为 DA-8031 作为早泄“按需”治疗药物的临床测试提供了线索。
