product name Vortioxetine
Description: Vortioxetine (as known as Lu AA21004) is a multimodal serotonergic agent, inhibits 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7 receptor and SERT with IC50 of 15 nM, 33 nM, 3.7 nM, 19 nM and 1.6 nM, respectively. Vortioxetine is an atypical antidepressant, and was approved in 2013 by the FDA for the treatment of major depressive disorder (MDD) in adults. Vortioxetine is a so-called “serotonin modulator and stimulator”.
References: J Med Chem. 2011 May 12;54(9):3206-21; J Pharmacol Exp Ther. 2012 Mar;340(3):666-75.
298.45
Formula
C18H22N2S
CAS No.
508233-74-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 10 mM
Water: <1 mg/mL
Ethanol:
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Lu-AA21004 inhibits recombinant human CYP1A2, CYP2C9, CYP2D6 and CYP3A4 with IC50 of 40 μM, 39 μM, 9.8 μM and 10 μM, respectively. Lu AA21004 is a partial h5-HT1B receptor agonist with EC50 of 460 nM and intrinsic activity of 22% using a whole-cell cAMP-based assay. Lu AA21004 binds to the r5-HT7 receptor with a Ki value of 200 nM and is a functional antagonist at the r5-HT7 receptor with an IC50 of 2 μM in an in vitro whole-cell cAMP assay. Kinase Assay: Cell Assay: |
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| In Vivo | For Lu-AA21004 the hepatic clearances and oral bioavailabilities in rats are found to be 7.1 (L/h)/kg and 16%. Lu-AA21004 (2.5 mg/kg, 5 mg/kg, or 10 mg/kg sc) increases the extracellular levels of 5-HT in the ventral hippocampus in conscious rats. Lu-AA21004 (5 mg/kg, or 10 mg/kg sc) also results in significantly higher basal levels of 5-HT in the medial prefrontal cortex (mPFC) after 3 days of treatment. Lu-AA21004 occupies SERT by 43% and 57% after 3 days of treatment with 5 mg/kg or 10 mg/kg in the rat medial prefrontal cortex. Lu AA21004 dose-dependent occupies 5-HT1B receptor and the SERT with ED50 of 3.2 mg/kg and 0.4 mg/kg in rats one hour after subcutaneous administration. Lu AA21004 affects the Bezold-Jarisch reflex in the rat dose dependently, inhibiting transient bradycardia with ED50 of 0.11 mg/kg. Lu AA21004 (2.5-10.0 mg/kg s.c.) increases extracellular levels of 5-HT, DA, and NA in the medial prefrontal cortex and in the ventral hippocampus in rats. Lu AA21004 (5 mg/kg s.c.) increases in the extracellular levels of 5-HT (200%) in the ventral hippocampus of rats with 41% occupancy at the SERT. Lu AA21004 (7.8 mg/kg s.c.) significantly decreases the immobility time in the FSL rats but not in the FRL rats. Lu AA21004 (8.0 mg/kg p.o.) produces an increase in social interaction as well as a small, but significant, increase in locomotor activity in rats. Lu AA21004 (7.9 mg/kg s.c.) shows a dose-dependent anxiolytic-like effect in the conditioned fear assay in rats. Vortioxetine (10 mg/kg) significantly increases freezing 60 min before acquisition in male Sprague-Dawley rats, suggesting enhanced contextual memory formation during acquisition and/or consolidation. Vortioxetine (5 mg/kg) also causes increased freezing rates during retention, an effect that reached statistical significance by post hoc tests. Vortioxetine (2.5 mg/kg or 5 mg/kg) prior to acquisition shows average exploration times of 29s and 33s for the novel object, respectively. Vortioxetine (10 mg/kg) significantly reduces nociception in rats, assessed as increased paw withdrawal latency. Vortioxetine at 5 and 10 mg/kg increases the levels of ACh to 224% and 204% of baseline 20 min after injection. |
| Animal model | Rats |
| Formulation & Dosage | Dissolved in 10% hydroxypropyl-β-cyclodextrin; 10 mg/kg; s.c. administration |
| References | J Med Chem. 2011 May 12;54(9):3206-21; J Pharmacol Exp Ther. 2012 Mar;340(3):666-75. |
