A new approach to 'on-demand' treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT 1A receptor antagonist and SSRI in rats.

Autor: Olivier JDA; Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands., Janssen JA; Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands., Esquivel-Franco DC; Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands., de Prêtre S; Atlas Pharmaceuticals BV, Bruges, Belgium., Olivier B; Atlas Pharmaceuticals BV, Bruges, Belgium.; Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
Jazyk: angličtina
Zdroj: Frontiers in neuroscience [Front Neurosci] 2023 Sep 13; Vol. 17, pp. 1224959. Date of Electronic Publication: 2023 Sep 13 (Print Publication: 2023).
DOI: 10.3389/fnins.2023.1224959
Abstrakt: Lifelong premature ejaculation (PE) in men lacks an adequate on-demand pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are used for PE they only work after chronic treatment, or if used on-demand, less adequately than chronic SSRI treatment. It has been shown that the addition of a behaviorally silent 5-HT 1A -receptor antagonist to an SSRI can generate acute inhibitory effects on male rat sexual behavior. Atlas987 is a selective 5-HT 1A -receptor antagonist with equal potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT 1A receptors in rat and human brain. To investigate whether Atlas987 together with the SSRI paroxetine, a combination called Enduro, induces acute inhibitory effects on male rat sexual behavior, we tested Enduro in Wistar rats in a dose-dependent manner. We first tested the 5-HT 1A receptor antagonist Atlas987 in 8-OH-DPAT induced serotonergic behavior in rats. Second, we tested Enduro in a dose-dependent manner in male sexual behavior. Third, we tested the effective time window of Enduro's action, and lastly, we measured the plasma levels of Atlas987 and paroxetine over an 8-h period. Results showed that Enduro acutely and dose-dependently reduced the number of ejaculations and increased the ejaculation latencies. The behavioral pattern induced reflected a specific effect on sexual behavior excluding non-specific effects like sedation or sensoric-motoric disturbances. The time-window of activity of Enduro showed that this sexual inhibitory activity was at least found in a 1-4 h' time window after administration. Plasma levels showed that in this time frame both Atlas987 and paroxetine are present. In conclusion, in rats, Enduro is successful in acutely inhibiting sexual behavior. These results may be therapeutically attractive as "on demand" treatment for life-long premature ejaculation in men.
Competing Interests: SP and BO were employed by the company Atlas Pharmaceuticals BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Olivier, Janssen, Esquivel-Franco, de Prêtre and Olivier.)
Databáze: MEDLINE
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