Research Laboratory, Dong-A Pharmaceutical Company, Giheung, Yongin, Gyeonggi, Korea.
Urology. 2011 Apr;77(4):1006.e17-21. doi: 10.1016/j.urology.2010.11.046. Epub 2011 Jan 22.
To evaluate the efficacy of DA-8031 against premature ejaculation, we performed in vitro and in vivo pharmacologic studies.
We used a monoamine transporter binding affinity assay, receptor binding affinity assay, monoamine reuptake inhibition assay, and serotonin uptake inhibition assay in platelets and chemically induced ejaculation models in rats.
The present study reports on the pharmacologic profile of the putative antipremature ejaculation drug, DA-8031. DA-8031 exhibits high affinity and selectivity to the serotonin transporter (Ki value 1.94 nM for 5-hydroxytryptamine transporter, 22 020 nM for norepinephrine transporter, and 77 679 nM for dopamine transporter) and potency to inhibit serotonin reuptake into the rat brain synaptosome in vitro (half maximal inhibitory concentration 6.52 nM for 5-hydroxytryptamine, 30.2 μM for norepinephrine, and 136.9 μM for dopamine). In the platelet serotonin uptake study, DA-8031 exhibited significant inhibition at oral doses of 10 and 30 mg/kg in a dose-dependent manner. In the sexual response studies, after oral and intravenous administration of DA-8031, ejaculation was significantly inhibited in both para-chloroamphetamine- and meta-chlorophenylpiperazine-mediated ejaculation models in rats.
The pharmacologic profiles observed in the present study suggest the potential for DA-8031 as a therapeutic agent useful in the treatment of premature ejaculation.
评估 DA-8031 治疗早泄的疗效，我们进行了体外和体内药理学研究。
我们使用单胺转运体结合亲和力测定、受体结合亲和力测定、单胺摄取抑制测定和血小板中 5-羟色胺摄取抑制测定，以及在大鼠化学诱导射精模型中进行了研究。
本研究报告了潜在抗早泄药物 DA-8031 的药理学特征。DA-8031 对 5-羟色胺转运体具有高亲和力和选择性（Ki 值为 1.94 nM，对去甲肾上腺素转运体为 22020 nM，对多巴胺转运体为 77679 nM），并能有效抑制大鼠脑突触小体中 5-羟色胺的摄取（半数最大抑制浓度为 6.52 nM，对去甲肾上腺素为 30.2 μM，对多巴胺为 136.9 μM）。在血小板 5-羟色胺摄取研究中，DA-8031 在 10 和 30 mg/kg 口服剂量下呈剂量依赖性显著抑制。在性反应研究中，在大鼠中，无论是给予苯丙胺还是间氯苯哌嗪后，口服和静脉给予 DA-8031 均可显著抑制射精。
本研究中观察到的药理学特征表明，DA-8031 有潜力成为一种治疗早泄的有用治疗剂。
