5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. Type: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7. They mediate both excitatory and inhibitory neurotransmission. Serotonin elicits its effects on sleep and waking by interacting with the seven major families of 5-HT receptors. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.

Vortioxetine (Lu AA 21004) is a 5-HT receptor modulator with high affinity for recombinant human 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7, noradrenergic β1 receptors and SERT.

Specifically, Vortioxetine is a 5-HT3A and 5-HT7 receptors antagonist. However, Vortioxetine exhibits partial agonist properties at the 5-HT1B receptor and agonist properties at the 5-HT1A receptor and has potent inhibitory effects on SERT. Importantly, Vortioxetine has the potential for neurological disease research, such as major depressive disorder. For example, Vortioxetine (2.5, 5, or 10 mg/kg sc) increases the extracellular levels of 5-HT in the ventral hippocampus in conscious rats. In addition, in rat microdialysis experiments, Vortioxetine (2.5-10.0 mg/kg s.c.) increases extracellular 5-HT, dopamine, and Noradrenaline in the medial prefrontal cortex and ventral hippocampus.

Vortioxetine (5 or 10 mg/kg/day; for 3 days) also results in significantly higher basal levels of 5-HT in the medial prefrontal cortex (mPFC). Furthermore, Vortioxetine shows a robust antidepressant- and anxiolytic-like profile in multiple preclinical assays, such as the mouse forced-swim and tail-suspension tests and the rat social interaction and conditioned-fear paradigms. In conclusion, Vortioxetine mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation.

To sum up, Vortioxetine is a 5-HT receptor modulator, and has the potential for neurological disease research.


[1] Benny Bang-Andersen, et al. J Med Chem. 2011 May 12;54(9):3206-21.
[2] A Mørk, et al. J Pharmacol Exp Ther. 2012 Mar;340(3):666-75.