Vortioxetine-d8 (Synonyms: Lu AA 21004 D8)

Vortioxetine-d₈ is intended for use as an internal standard for the quantification of vortioxetine by GC- or LC-MS. Vortioxetine is a multimodal serotonergic agent that acts as a serotonin reuptake inhibitor (K_i = 1.6 nM) and binds to the 5-HT_1A, 5-HT_1B, 5-HT_3A, and 5-HT₇ receptors (K_is = 15, 33, 3.7, and 19 nM, respectively).¹ It also binds to the β₁-adrenergic receptor (K_i = 46 nM). It acts as an antagonist at 5-HT_3A and 5-HT₇, a partial agonist at 5-HT_1B, and a full agonist at 5-HT_1A receptors. Vortioxetine is selective for the serotonin transporter (SERT) over the dopamine and norepinephrine transporters (IC₅₀s = 5.3, 890, and 140 nM, respectively). It has affinity for histamine H₂, melanocortin 4, β₂-adrenergic, 5-HT_2C, and 5-HT₆ receptors with K_i values greater than 180 nM, but it is selective over the majority of targets in a panel of 75 ion channels, G protein-coupled receptors, enzymes, and transporters. Vortioxetine (5 or 10 mg/kg per day) increases 5-HT levels in vivo in rat brain and decreases occupancy at SERT. At acute and chronic doses of 5 mg/kg, but not 10 mg/kg, it increases the time mice spend in the center of the open field test, increases mobility in the forced swim test, and decreases the latency to feed in the novelty suppressed feeding test.² It also increases proliferation and survival of adult-born granule cells in the hippocampus. Formulations containing vortioxetine have been used in the treatment of major depressive disorder.

1.Bang-Andersen, B., Ruhland, T., JØrgensen, M., et al.Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A novel multimodal compound for the treatment of major depressive disorderJ. Med Chem.54(9)3206-3221(2011) 2.Guilloux, J.P., Mendez-David, I., Pehrson, A., et al.Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in miceNeuropharmacology73147-159(2013)