Vilazodone-d₈ hydrochloride  (Synonyms: EMD 68843-d8; SB659746A-d8)

Vilazodone-d₈ hydrochloride is deuterated labeled Vilazodone (HY-14262). Vilazodone (EMD 68843; SB 659746A) is a potent, selective and orally active serotonin reuptake inhibitor (SSRI) and partial 5-HT₁A receptor agonist. Vilazodone exhibits antidepressant efficacy in vivo can be used for the research of major depressive disorder (MDD) and affective disorders^[1][2].

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Vilazodone shows an IC₅₀ of 0.2 nM at the human 5-HT₁A receptor and 0.5 nM for the SERT. Vilazodone preferentially binds to the high agonist affinity state of human 5-HT₁A receptors, and it displays high affinity (pK_i≥9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5-HT_1A receptors.
Vilazodone acts as a high efficacy partial agonist at 5-HT₁A receptors. In [³⁵S]GTPγS binding studies in Sf9 cells expressing h5-HT₁A receptors, a single concentration of Vilazodone (100nM) increases basal binding by approximately 70% of that produced by the full 5-HT₁A receptor agonist, 8‐OH‐PIPAT.
In [³⁵S]GTPγS binding studies in rat hippocampal membranes, Vilazodone acts as a potent 5‐HT_1A receptor partial agonist with a pEC₅₀ of 8.1 and an intrinsic activity of 0.61.
Vilazodone acts as a potent 5‐HT reuptake inhibitor in rat and guinea pig cortex. In LLCPK cells expressing human SERT, whereby vilazodone inhibits [³H]5‐HT uptake with a pIC₅₀ of 8.8^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Vilazodone (intraperitoneal injection; 3 mg/kg ; single dose) produces increases in extracellular levels of 5‐HT in both the frontal cortex (FC) and ventral hippocampus (vHipp) of rats in vivo microdialysis studies. Maximum increases are observed at 3 mg/kg and reaches 527% and 558% of preinjection baseline values in the FC and vHipp, respectively^[3].
Vilazodone (oral gavage ;55 mg/kg ; single dose) inhibits stress‐induced vocalizations in the rat ultrasonic vocalizations test at 120 and 210 min post dose^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

486.04

C₂₆H₂₀D₈ClN₅O₂

163521-12-8

NC(C1=CC2=C(C=CC(N3CCN(C([2H])([2H])C([2H])([2H])C([2H])([2H])C([2H])([2H])C4=CNC5=CC=C(C=C54)C#N)CC3)=C2)O1)=O.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Cruz MP. Vilazodone HCl (Viibryd): A Serotonin Partial Agonist and Reuptake Inhibitor For the Treatment of Major Depressive Disorder. P T. 2012 Jan;37(1):28-31.  [Content Brief]

  [3]. Lee A. Dawson et al. Vilazodone: A 5-HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders CNS Neuroscience & Therapeutics Volume 15, Issue 2, pages 107-117, June 2009