Orion Corporation, Orion Pharma R&D, Turku, Finland.
Escuela Nacional de Estudios Superiores, Unidad Juriquilla UNAM, Querétaro, México.
J Sex Med. 2021 Oct;18(10):1677-1689. doi: 10.1016/j.jsxm.2021.07.010. Epub 2021 Sep 5.
Premature ejaculation is the most common sexual dysfunction in young men, and it often leads to reduced relationship satisfaction and quality of life.
To determine the role of central and peripheral α-adrenoceptors in the control of ejaculation and sexual incentive motivation in rats.
Sexual incentive motivation was studied in a large arena in which a male subject could choose between approaching and remaining close to a sexually receptive female or another male. Sexual behavior was studied in standard observation cages in which a male was allowed to freely interact with a receptive female for 30 minutes. Two highly selective agonists at the α-adrenoceptors, tasipimidine and fadolmidine, were administered before the tests. Low peripheral doses of fadolmidine have been reported to have effects mainly outside of the central nervous system, whereas at large doses also the central effects are evident.
The time spent close to the receptive female in relation to the time spent with the male and measures of ambulatory activity were obtained from the test for sexual incentive motivation, while the habitual parameters of sexual behavior were recorded with the copulation test.
Tasipimidine prolonged ejaculation latency and the interintromission interval at the dose of 200 µg/kg when data from fast-ejaculating rats were used. No other sexual parameter was modified. A dose of 100 µg/kg was ineffective. There was no consistent effect on sexual incentive motivation, although modest sedation was observed. Fadolmidine, a drug that does not easily penetrate the blood-brain barrier, had no effect on sexual incentive motivation at any of the doses used (3, 30, and 100 µg/kg). The largest dose had clear sedative effects. The lower doses had no systematic effect on sexual behavior, not even when only fast or very fast ejaculating males were analyzed.
The findings are relevant to the search for treatments for premature ejaculation that are specific enough to selectively delay ejaculation.
STRENGTHS & LIMITATIONS: The procedures used here are standard in the field and yield the most reliable data. Whether the effects observed in male rats are directly transferrable to men can only be determined through clinical studies.
The observation that drugs acting at central but not peripheral α-adrenoceptors prolong ejaculation latency without affecting any other parameter of sexual behavior or sexual incentive motivation suggests that this kind of drug may be suitable for treating premature ejaculation. Jyrki L., Elisa V.-A., Xi C., et al. Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. J Sex Med 2021;18:1677-1689.
早泄是年轻男性最常见的性功能障碍，常导致性关系满意度和生活质量下降。
确定中枢和外周 α-肾上腺素能受体在控制大鼠射精和性激励动机中的作用。
在一个大型竞技场中研究性激励动机，雄性实验对象可以选择接近和靠近性接受的雌性或另一只雄性。在标准观察箱中研究性行为，雄性可以自由地与接受的雌性互动 30 分钟。两种高度选择性的 α-肾上腺素能受体激动剂，塔西皮米丁和法多米定，在测试前给药。据报道，外周低剂量的法多米定会对中枢神经系统以外的部位产生影响，而大剂量时也会产生中枢效应。
从性激励动机测试中获得接近接受雌性的时间与接近雄性的时间以及活动量的测量值，而习惯性性行为参数则通过交配测试记录。
观察到，当使用快速射精的大鼠数据时，药物塔西皮米丁在 200μg/kg 剂量下延长了射精潜伏期和间隔期。其他性参数没有改变。剂量为 100μg/kg 时无效。没有对性激励动机产生一致的影响，尽管观察到适度镇静。法多米定不易穿透血脑屏障，在使用的任何剂量（3、30 和 100μg/kg）下均对性激励动机没有影响。最大剂量有明显的镇静作用。较低剂量对性行为没有系统影响，即使只分析快速或非常快速射精的雄性也是如此。
这些发现与寻找特异性足以延迟射精的治疗早泄的方法有关。
这里使用的程序是该领域的标准程序，可产生最可靠的数据。在雄性大鼠中观察到的效果是否可以直接转移到男性身上，只能通过临床研究来确定。
观察到作用于中枢而非外周 α-肾上腺素能受体的药物延长射精潜伏期而不影响性行为或性激励动机的任何其他参数，表明这种药物可能适合治疗早泄。
