MP47-02 DAPOXETINE INHIBITS ERECTILE RESPONSES TO STIMULATION OF THE CAVERNOUS NERVE IN RATS: A NEW HYPOTHESIS FOR ITS EFFECTS ON EJACULATION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-02 DAPOXETINE INHIBITS ERECTILE RESPONSES TO STIMULATION OF THE CAVERNOUS NERVE IN RATS: A NEW HYPOTHESIS FOR ITS EFFECTS ON EJACULATION Stefano Palea, Celine Rouget, Philippe Lluel, and Julien Allard Stefano PaleaStefano Palea More articles by this author , Celine RougetCeline Rouget More articles by this author , Philippe LluelPhilippe Lluel More articles by this author , and Julien AllardJulien Allard More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1455AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Selective Serotonin Reuptake Inhibitors (SSRI) like paroxetine and fluoxetine are known to induce erectile dysfunction in humans and rats. Dapoxetine, a selective SSRI, is approved in Europe for the management of premature ejaculation. The aim of this study was to assess the impact of dapoxetine on (1) erectile responses induced by electrical stimulation (ES) of the cavernous nerve and (2) on smooth muscle relaxations induced by sodium nitroprusside (SNP) or sildenafil (SF) in the isolated corpus cavernosum (CC). Methods Wistar rats were anaesthetized with urethane. The carotid artery, penis and jugular vein were catheterized for blood pressure and intracavernous pressure recordings (BP and ICP) and drug injection, respectively. The right cavernous nerve was mounted on bipolar stimulating electrodes. ES (3, 6 and 9 Hz) were performed before and at 4, 24, 44 and 64 min after intravenous (i.v.) injection of 1 or 3 mg/kg dapoxetine or saline in 3 independent groups of 6 animals. ICP values were normalized to BP. For in vitro experiments, CC strips from Wistar rats were mounted under 0.5 g of tension in organ baths with a modified Krebs solution. After 60 min of equilibration, dapoxetine 1 μM (or its solvent) was incubated for 20 min. Strips were then exposed to norepinephrine 30 μM. When contractions reached a plateau, cumulative concentration-response curves to SNP, SF or their common solvent were constructed. Results Erectile responses were dose-dependently decreased by dapoxetine from 4 to 44 min post-dosing at all frequencies of ES. The mean of ICPmean/BP at 6 Hz was 0.47±0.01 in the 3 groups before injection. At 44 min post-injection, ICPmean/BP at 6 Hz was 0.43±0.06, 0.30±0.08 and 0.13±0.04 after vehicle, 1 mg/kg and 3 mg/kg dapoxetine (P<0.01 vs vehicle) respectively. Similar decreases were observed for ICPmax/BP. On the isolated CC, dapoxetine had no inhibitory effect on SNP or SF-mediated relaxations up to 1 μM. In addition, dapoxetine had no contractile or relaxant effects on the basal smooth muscle tone up to 10 and 100 μM, respectively Conclusions Erectile responses were inhibited by dapoxetine at 1 and 3 mg/kg i.v. This inhibitory activity might be one of the mechanisms by which dapoxetine delays ejaculation in patients suffering from premature ejaculation. Furthermore, in vitro studies demonstrated that the inhibitory activity of dapoxetine on penile erection cannot be explained by an action at the peripheral level, suggesting a central nervous system-related mechanism. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e519 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Stefano Palea More articles by this author Celine Rouget More articles by this author Philippe Lluel More articles by this author Julien Allard More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...