Vortioxetine is a 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 has shown positive effects on cognitive dysfunction which likely involve 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 data and a literature review of the current understanding of the interaction between the histaminergic and serotonergic systems as well as the role of histamine on cognitive function, the authors propose that vortioxetine stimulates the tuberomammilary nucleus and enhances histaminergic neurotransmission via the orexinergic system. This, in turn, may contribute to vortioxetine’s positive effects on cognitive function.
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Smagin GN, Song D, Budac DP, Waller JA, Li Y, Pehrson AL, Sánchez C: Histamine may contribute to vortioxetine’s procognitive effects; possibly through an orexigenic mechanism. Prog. Neuropsychopharmacol. Biol. Psychiatry [ Epub ahead of print; March 2, 2016; doi: 10.1016/j.pnpbp.2016.03.001 ].
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http://www.ncbi.nlm.nih.gov/pubmed/26945513