title: Vilazodone does not inhibit sexual behavior in male rats in contrast to paroxetine: A role for 5-HT1A receptors?
abstract: Vilazodone (VLZ) is a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. In preclinical studies, VLZ had significantly lower sexual side effects than SSRIs and reduced serotonin transporter (SERT) levels in forebrain regions. In the current study, once-daily paroxetine (PAR, 10 mg/kg), VLZ (10 mg/kg), PAR + buspirone (BUS, 3 mg/kg; a 5-HT1A partial agonist), or vehicle (VEH) was administered to male rats for 2 weeks then switched for 7 days (eg, PAR switched to VLZ, PAR + BUS, or VEH). Sexual behavior (eg, ejaculation frequency and latency) was evaluated 1-hr postdose on days 1, 7, 14, and 21. After 2 weeks, treatment with PAR but not VLZ resulted in a significant decrease in sexual behavior. In a 30-min test, the range of ejaculation frequency was 3.08-3.5 with VLZ and 1.00-1.92 with PAR (P < 0.05 vs VEH). After switching from PAR to VEH, PAR + BUS, or VEH, sexual behaviors were normalized to control levels. In contrast, the switch from VLZ to PAR resulted in reduced sexual behaviors. This preclinical study showed that unlike PAR, an SSRI with no 5-HT1A receptor activity, initial treatment with VLZ did not result in sexual side effects at therapeutically relevant doses. Results in male rats switched from PAR to VLZ or PAR + BUS strongly suggest that activation of 5-HT1A receptors may mitigate the sexual side effects associated with conventional SSRIs.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: R.S.Oosting@uu.nl.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Johnny S W
authors.initials: JSW
authors.lastname: Chan
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Groningen Institute for Evolutionary Life Sciences (GELIFES), Rijksuniversiteit Groningen, The Netherlands.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Forest Research Institute (an Allergan affiliate), 1900 Plaza Five, Jersey City, NJ 07311, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D054333:Drug Partial Agonism; D005260:Female; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000069503:Vilazodone Hydrochloride / Q000494:pharmacology*
chemical_list: D017374:Paroxetine; D044282:Receptor, Serotonin, 5-HT1A; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride
keywords: Antidepressant; Partial agonism; Preclinical; Serotonin receptor