Histamine may contribute to vortioxetine's procognitive effects; possibly through an orexigenic mechanism.
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.
['Smagin|Gennady N|GN|', 'Song|Dekun|D|', 'Budac|David P|DP|', 'Waller|Jessica A|JA|', 'Li|Yan|Y|', 'Pehrson|Alan L|AL|', 'Sánchez|Connie|C|']
D000818:Animals D003071:Cognition D060825:Cognitive Dysfunction D006632:Histamine D007026:Hypothalamic Area, Lateral D000068797:Orexins D010879:Piperazines D018490:Serotonin Agents D013440:Sulfides D009435:Synaptic Transmission D000078784:Vortioxetine
Histamine Antidepressant Cognition 5-HT receptors