Department of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
Laboratory of Reproductive and Developmental Biology and Toxicology (ReproTox), Department of Morphology, State University of São Paulo (UNESP), Botucatu, Brazil.
J Sex Med. 2020 Jun;17(6):1060-1071. doi: 10.1016/j.jsxm.2020.02.027. Epub 2020 Mar 29.
Lorcaserin is an anti-obesity drug whose weight loss effect results from 5-hydroxytryptamin (5-HT) receptors activation. The 5-HT receptor was shown to participate in the physiological control of ejaculation, but no data addressing a putative effect of lorcaserin on ejaculation exist.
To investigate the effects of lorcaserin in different in vitro and in vivo experimental models of ejaculation in rats.
Contractile responses to lorcaserin in rat seminal emission organs in vitro (prostatic and epididymal vas deferens, cauda epididymis, and seminal vesicles), analysis of male rat copulatory behavior, and electromyographic recording of bulbospongiosus muscle in anesthetized animals were studied.
The main outcome measures included in vitro contraction of seminal emission organs and evaluation of the male rat copulatory behavior. The male rat sexual behavior in terms of copulation latency, ejaculation latency, mount and intromission frequency, and ejaculation frequency of sexually experienced adult male rats with a receptive female were also recorded.
Lorcaserin (1.0 nM to 1.0 mM) had no significant effects on the in vitro contractility of seminal emission organs smooth muscle (cauda epididymis, vas deferens, and seminal vesicles). On the other hand, lorcaserin administration (0.3-1.0 mg/kg, intravenous) induced ejaculation in anesthetized rats, which was prevented by the 5-HT-selective antagonist SB 242084 (0.1 and 0.3 mg/kg, intravenous). Single-dose treatment of non-anesthetized male rats with lorcaserin (1.0, 4.0, or 10 mg/kg, per os) induced non-copulating ejaculations in sexually naïve rats. Lorcaserin also had pro-ejaculation effects by decreasing the ejaculation threshold of copulating rats by half. The pro-ejaculatory effects of lorcaserin were reversible as the ejaculation threshold of treated rats recovered after a 1-week washout period.
Due to its reported clinical safety, repurposing lorcaserin for the treatment of delayed ejaculation may be suggested.
STRENGTHS & LIMITATIONS: The pro-ejaculatory effect of lorcaserin administration and the role of 5-HT were demonstrated in different experimental models of ejaculation in rats. The lack of studies in putative experimental models of delayed ejaculation is a limitation of this study.
Our results demonstrate that the clinically approved 5-HT agonist lorcaserin is a strong facilitator of ejaculation in rats. de Almeida Kiguti LR, Pacheco TL, Antunes E, et al. Lorcaserin Administration has Pro-Ejaculatory Effects in Rats via 5-HT2C Receptors Activation: A Putative Pharmacologic Strategy to Delayed Ejaculation? J Sex Med 2020;17:1060-1071.
洛卡塞嗪是一种抗肥胖药物，其减肥效果来自于 5-羟色胺（5-HT）受体的激活。5-HT 受体被证明参与了射精的生理控制，但尚无关于洛卡塞嗪对射精可能产生影响的相关数据。
研究洛卡塞嗪对大鼠不同体外和体内射精实验模型的影响。
在体外（前列腺和附睾输精管、附睾尾部和精囊）研究洛卡塞嗪对大鼠精液排放器官的收缩反应，分析雄性大鼠的交配行为，并对麻醉动物的球海绵体肌进行肌电图记录。
主要观察指标包括体外精液排放器官的收缩和雄性大鼠交配行为的评估。还记录了有性经验的成年雄性大鼠与接受雌性大鼠交配时的交配潜伏期、射精潜伏期、交配和插入频率以及射精频率等雄性大鼠性行为参数。
洛卡塞嗪（1.0 nM 至 1.0 mM）对精液排放器官平滑肌（附睾尾部、输精管和精囊）的体外收缩没有显著影响。另一方面，洛卡塞嗪（0.3-1.0 mg/kg，静脉注射）诱导麻醉大鼠射精，而 5-HT 选择性拮抗剂 SB 242084（0.1 和 0.3 mg/kg，静脉注射）可预防这种作用。单次给予非麻醉雄性大鼠洛卡塞嗪（1.0、4.0 或 10 mg/kg，口服）可诱导初次交配的雄性大鼠出现非交配性射精。洛卡塞嗪还可通过将交配大鼠的射精阈值降低一半来产生促射精作用。洛卡塞嗪的促射精作用是可逆的，因为接受治疗的大鼠在 1 周洗脱期后恢复了射精阈值。
由于其临床安全性已得到证实，因此可以考虑将洛卡塞嗪重新用于治疗延迟射精。
本研究的局限性在于缺乏对延迟射精的可能实验模型的研究。
本研究结果表明，临床批准的 5-HT 激动剂洛卡塞嗪可显著促进大鼠射精。de Almeida Kiguti LR、Pacheco TL、Antunes E 等。洛卡塞嗪通过激活 5-HT2C 受体具有促射精作用：一种治疗延迟射精的潜在药理学策略？J 性医学 2020；17：1060-1071。
