A New Approach for On-Demand Premature Ejaculation

For quite some time, off-label use of selective serotonin reuptake inhibitors (SSRIs) is the primary choice of pharmacological treatment of lifelong premature ejaculation (PE). Unfortunately these treatments do not exert on-demand effects and have to be taken chronically. Although several new approaches have been introduced the last decade, on-demand treatment appears a big bottleneck (Olivier and Olivier, 2019). In our research on sexual behavior in male rats, we developed a model for male sexual behavior that is able to replicate the effects of SSRIs in men with lifelong premature ejaculation. After extensive weekly sexual training of large cohorts of male Wistar rats, a portion of them displays stable and high levels of sexual behavior in 30-min. tests with an estrus female, presented by very stable levels of high ejaculation frequencies and short ejaculation latencies. These fast-ejaculating rats are used for drug testing. SSRIs exert the profile as shown in men with lifelong PE, no acute effects but only sexual inhibition after chronic administration. We found that adding a very selective 5-HT1A receptor antagonist Atlas987 (10-mg/kg IP) to the SSRI paroxetine (5-mg/kg IP) led to acute (on-demand) inhibition of sexual behavior in male rats, evidenced by a strong reduction in the ejaculation frequency and doubling of ejaculation latency. A similar profile was found with the reference 5-HT1A-receptor antagonist WAY100,635 (0.3 mg/kg IP) plus 5 mg/kg paroxetine.