title: [Pharmacological properties of vortioxetine and its pre-clinical consequences].
abstract: Selective Serotonin Reuptake Inhibitors (SSRIs) are extensively used for the treatment of major depressive disorder (MDD). SSRIs are defined as indirect receptor agonists since the activation of postsynaptic receptors is a consequence of an increase in extracellular concentrations of serotonin (5-HT) mediated by the blockade of serotonin transporter. The activation of some serotoninergic receptors (5-HT1A, post-synaptic, 5-HT1B post-synaptic, 5-HT2B, and 5-HT4), but not all (5-HT1A, pre-synaptic, 5-HT1B pre-synaptic, 5-HT2A, 5-HT2C, 5-HT3, and probably 5-HT6), induces anxiolytic/antidepressive - like effects. Targetting specifically some of them could potentially improve the onset of action and/or efficacy and/or prevent MD relapse. Vortioxetine (Brintellix, 1- [2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a novel multi-target antidepressant drug approved by the Food and Drug Administration (FDA) and by European Medicines Agency. Its properties are markedly different from the extensively prescribed SSRIs. Compared to the SSRIs, vortioxetine is defined as a multimodal antidepressant drug since it is not only a serotonin reuptake inhibitor, but also a 5-HT1D, 5-HT3, 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist and 5-HT1A receptor agonist. This specific pharmacological profile enables vortioxetine to affect not only the serotoninergic and noradrenergic systems, but also the histaminergic, cholinergic, gamma-butyric acid (GABA) ergic and glutamatergic ones. Thus, vortioxetine not only induces antidepressant-like or anxiolytic-like activity but also improves cognitive parameters in several animal models. Indeed, vortioxetine was shown to improve working memory, episodic memory, cognitive flexibility and spatial memory in young adult rodents and also in old animal models. These specific effects of the vortioxetine are of interest considering that cognitive dysfunction is a common comorbidity to MDD. Altogether, even though this molecule still needs to be investigated further, especially in the insufficient-response to antidepressant drugs, vortioxetine is already an innovative therapeutic option for the treatment of major depression.
authors.affiliation: Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France; DJD et LT ont contribué de façon équivalente à l'élaboration du manuscrit.
authors.forename: D J
authors.initials: DJ
authors.lastname: David
authors.affiliation: Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France; DJD et LT ont contribué de façon équivalente à l'élaboration du manuscrit.
authors.forename: L
authors.initials: L
authors.lastname: Tritschler
authors.affiliation: Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Guilloux
authors.affiliation: Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Gardier
authors.affiliation: Lundbeck Research USA, Inc., 215 College Road, 07652 Paramus, NJ, United States.
authors.forename: C
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Service Hospitalo-Universitaire - Addictologie, Centre Hospitalier Sainte Anne, 1, rue Cabanis, 75674 Paris cedex 14, France. Electronic address: raphael.gaillard@normalesup.org.
authors.forename: R
authors.initials: R
authors.lastname: Gaillard
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy; D006801:Humans; D010879:Piperazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D000078784:Vortioxetine
chemical_list: D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Antidepressant; Antidépresseur; Cognition; Depression; Dépression; Multimodal; Preclinical; Préclinique; Vortioxetine