title: The triple monoaminergic reuptake inhibitor DOV 216,303 has antidepressant effects in the rat olfactory bulbectomy model and lacks sexual side effects.
abstract: Current antidepressants have a delayed onset of action and disturbing side effects, including inhibition of sexual behavior. It is hypothesized that novel drugs, hitting multiple disease-relevant targets, may yield a new generation of superior antidepressants. One such approach is simultaneous inhibition of serotonin, norepinephrine and dopamine transporters. We tested the triple uptake inhibitor (TUI), DOV 216,303 (5, 10 and 20 mg/kg) after 1, 7 and 14 days administration in the olfactory bulbectomized (OBX) rat depression model, and in a model of rat sexual behavior to detect putative sexual side effects. Chronic, but not acute treatment of DOV 216,303 (20 mg/kg) normalized OBX-induced hyperactivity in the open field, similar to the effect of imipramine (20 mg/kg). None of the doses of DOV 216,303 had any effect on sexual behavior at any time point. The results indicate that DOV 216,303 displays antidepressant efficacy and is devoid of sexual side effects.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Breuer
authors.forename: J S W
authors.initials: JS
authors.lastname: Chan
authors.forename: R S
authors.initials: RS
authors.lastname: Oosting
authors.forename: L
authors.initials: L
authors.lastname: Groenink
authors.forename: S M
authors.initials: SM
authors.lastname: Korte
authors.forename: U
authors.initials: U
authors.lastname: Campbell
authors.forename: R
authors.initials: R
authors.lastname: Schreiber
authors.forename: T
authors.initials: T
authors.lastname: Hanania
authors.forename: E M S
authors.initials: EM
authors.lastname: Snoeren
authors.forename: M
authors.initials: M
authors.lastname: Waldinger
authors.forename: B
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009830:Olfactory Bulb / Q000601:surgery*; D017374:Paroxetine / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018709:Statistics, Nonparametric
chemical_list: C474071:1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride; D000928:Antidepressive Agents; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017374:Paroxetine