title: Histamine may contribute to vortioxetine's procognitive effects; possibly through an orexigenic mechanism.
abstract: Vortioxetine is a novel multimodal antidepressant that acts as a serotonin (5-HT)3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B receptor partial agonist; 5-HT1A receptor agonist; and 5-HT transporter inhibitor in vitro. In preclinical and clinical studies vortioxetine demonstrates positive effects on cognitive dysfunction. Vortioxetine's effect on cognitive function likely involves the modulation of several neurotransmitter systems. Acute and chronic administration of vortioxetine resulted in changes in histamine concentrations in microdialysates collected from the rat prefrontal cortex and ventral hippocampus. Based on these results and a literature review of the current understanding of the interaction between the histaminergic and serotonergic systems and the role of histamine on cognitive function, we hypothesize that vortioxetine through an activation of the orexinergic system stimulates the tuberomammilary nucleus and enhances histaminergic neurotransmission, which contributes to vortioxetine's positive effects on cognitive function.
authors.affiliation: Neuroinflammation Biology In vivo, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: Gennady N
authors.initials: GN
authors.lastname: Smagin
authors.affiliation: Neuroinflammation Biology In vivo, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: Dekun
authors.initials: D
authors.lastname: Song
authors.affiliation: Bioanalysis, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Budac
authors.affiliation: Brintellix Science Team, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Waller
authors.affiliation: Brintellix Science Team, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Brintellix Science Team, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Pehrson
authors.affiliation: Brintellix Science Team, Lundbeck Research USA, 215 College Rd, Paramus, NJ, USA. Electronic address: cs@lundbeck.com.
authors.forename: Connie
authors.initials: C
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D006632:Histamine / Q000378:metabolism*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects*; D000068797:Orexins / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D000078784:Vortioxetine
chemical_list: D000068797:Orexins; D010879:Piperazines; D018490:Serotonin Agents; D013440:Sulfides; D000078784:Vortioxetine; D006632:Histamine
keywords: 5-HT receptors; Antidepressant; Cognition; Histamine