Identification

Name
Vortioxetine
Accession Number
DB09068  (DB05700)
Type
Small Molecule
Groups
Approved, Investigational
Description

Vortioxetine is an atypical antipsychotic and antidepressant indicated for the treatment of major depressive disorder (MDD). It is classified as a serotonin modulator and simulator (SMS) as it has a multimodal mechanism of action towards the serotonin neurotransmitter system whereby it simultaneously modulates one or more serotonin receptors and inhibits the reuptake of serotonin. More specifically, vortioxetine acts via the following biological mechanisms: as a serotonin reuptake inhibitor (SRI) through inhibition of the serotonin transporter, as a partial agonist of the 5-HT1B receptor, an agonist of 5-HT1A, and an antagonist of the 5-HT3, 5-HT1D, and 5-HT7 receptors. SMSs were developed because there are many different subtypes of serotonin receptors, however, not all of these receptors appear to be involved in the antidepressant effects of SRIs. Some serotonin receptors seem to play a relatively neutral or insignificant role in the regulation of mood, but others, such as 5-HT1A autoreceptors and 5-HT7 receptors, appear to play an oppositional role in the efficacy of SRIs in treating depression.

Structure
Thumb
Synonyms
  • Vortioxetina
  • Vortioxétine
  • vortioxetinum
External IDs
Lu AA21004 / Lu-AA21004 / LuAA21004
Product Ingredients
IngredientUNIICASInChI Key
Vortioxetine hydrobromideTKS641KOAY960203-27-4VNGRUFUIHGGOOM-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BrintellixTablet, film coated10 mg/1OralAvera McKennan Hospital2015-06-05Not applicableUs69189 056020180907 15195 gvj4rl
BrintellixTablet, film coated10 mg/1OralTakeda2013-10-02Not applicableUs64764 0560 30 nlmimage10 5a3a2d71
BrintellixTablet, film coated20 mg/1OralTakeda2013-10-02Not applicableUs
BrintellixTablet, film coated5 mg/1OralTakeda2013-10-02Not applicableUs
BrintellixTablet, film coated15 mg/1OralTakeda2013-10-02Not applicableUs
TrintellixTablet15 mgOralLundbeck Inc.Not applicableNot applicableCanada
TrintellixTablet5 mgOralLundbeck Inc.2014-10-28Not applicableCanada
TrintellixTablet, film coated15 mg/1OralTakeda Pharmaceuticals America, Inc.2013-10-022016-08-05Us
TrintellixTablet, film coated10 mg/1OralTakeda2013-10-02Not applicableUs
TrintellixTablet20 mgOralLundbeck Inc.2014-10-28Not applicableCanada
Categories
UNII
3O2K1S3WQV
CAS number
508233-74-7
Weight
Average: 298.45
Monoisotopic: 298.15036989
Chemical Formula
C18H22N2S
InChI Key
YQNWZWMKLDQSAC-UHFFFAOYSA-N
InChI
InChI=1S/C18H22N2S/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20/h3-8,13,19H,9-12H2,1-2H3
IUPAC Name
1-{2-[(2,4-dimethylphenyl)sulfanyl]phenyl}piperazine
SMILES
CC1=CC=C(SC2=CC=CC=C2N2CCNCC2)C(C)=C1

Pharmacology

Indication

Vortioxetine is indicated for the treatment of major depressive disorder (MDD).

Associated Conditions
Pharmacodynamics

Vortioxetine binds with high affinity to the human serotonin transporter (Ki=1.6 nM), but not to the norepinephrine (Ki=113 nM) or dopamine (Ki>1000 nM) transporters. Vortioxetine potently and selectively inhibits reuptake of serotonin by inhibition of the serotonin transporter (IC50=5.4 nM). Specifically, vortioxetine binds to 5­HT3 (Ki=3.7 nM), 5­HT1A (Ki=15 nM), 5­HT7 (Ki=19 nM), 5­HT1D (Ki=54 nM), and 5­HT1B (Ki=33 nM), receptors and is a 5­HT3, 5­HT1D, and 5­HT7 receptor antagonist, 5­HT1B receptor partial agonist, and 5­HT1A receptor agonist.

Mechanism of action

Vortioxetine is classified as a serotonin modulator and simulator (SMS) as it has a multimodal mechanism of action towards the serotonin neurotransmitter system whereby it simultaneously modulates one or more serotonin receptors and inhibits the reuptake of serotonin. More specifically, vortioxetine acts via the following biological mechanisms: as a serotonin reuptake inhibitor (SRI) through inhibition of the serotonin transporter, while also acting as a partial agonist of the 5-HT1B receptor, an agonist of 5-HT1A, and antagonist of the 5-HT3, 5-HT1D, and 5-HT7 receptors.

TargetActionsOrganism
ASodium-dependent serotonin transporter
inhibitor
Human
A5-hydroxytryptamine receptor 3A
antagonist
Human
A5-hydroxytryptamine receptor 7
antagonist
Human
A5-hydroxytryptamine receptor 1B
partial agonist
Human
A5-hydroxytryptamine receptor 1A
agonist
Human
UBeta-1 adrenergic receptor
ligand
Human
Usolute carrier family 6 member 2
blocker
Human
Absorption

The maximal plasma vortioxetine concentration (Cmax) after dosing is reached within 7 to 11 hours postdose. Absolute bioavailability is 75%. No effect of food on the pharmacokinetics was observed.

Volume of distribution

The apparent volume of distribution of vortioxetine is approximately 2600 L, indicating extensive extravascular distribution.

Protein binding

The plasma protein binding of vortioxetine in humans is 98%, independent of plasma concentrations. No apparent difference in the plasma protein binding between healthy subjects and subjects with hepatic (mild, moderate) or renal (mild, moderate, severe, ESRD) impairment is observed.

Metabolism

Vortioxetine is extensively metabolized primarily through oxidation via cytochrome P450 isozymes CYP2D6, CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8 and CYP2B6 and subsequent glucuronic acid conjugation. CYP2D6 is the primary enzyme catalyzing the metabolism of vortioxetine to its major, pharmacologically inactive, carboxylic acid metabolite, and poor metabolizers of CYP2D6 have approximately twice the vortioxetine plasma concentration of extensive metabolizers.

Route of elimination

Following a single oral dose of [14C]­labeled vortioxetine, approximately 59% and 26% of the administered radioactivity was recovered in the urine and feces, respectively as metabolites. Negligible amounts of unchanged vortioxetine were excreted in the urine up to 48 hours.

Half life

Mean terminal half­life is approximately 66 hours

Clearance
Not Available
Toxicity

The most commonly reported adverse effects during clinical trials were nausea, diarrhea, and dry mouth. The FDA label includes a blackbox warning for the following risks and complications: serotonin syndrome, especially when combined with other serotonergic agents; increased risk of abnormal bleeding, especially when combined with NSAIDs, aspirin, or other drugs that affect coagulation; activation of mania/hypomania; hyponatremia; and suicidal thoughts and behaviour in children, adolescents, and young adults.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower maximum dose.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Vortioxetine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Vortioxetine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Vortioxetine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Vortioxetine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Vortioxetine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Vortioxetine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Vortioxetine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Vortioxetine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Vortioxetine is combined with 5-methoxy-N,N-dimethyltryptamine.
6-Deoxyerythronolide BThe metabolism of Vortioxetine can be decreased when combined with 6-Deoxyerythronolide B.
Food Interactions
Not Available

References

General References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
  2. Stenkrona P, Halldin C, Lundberg J: 5-HTT and 5-HT(1A) receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects. Eur Neuropsychopharmacol. 2013 Oct;23(10):1190-8. doi: 10.1016/j.euroneuro.2013.01.002. Epub 2013 Feb 18. [PubMed:23428337]
  3. Mork A, Montezinho LP, Miller S, Trippodi-Murphy C, Plath N, Li Y, Gulinello M, Sanchez C: Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav. 2013 Apr;105:41-50. doi: 10.1016/j.pbb.2013.01.019. Epub 2013 Feb 1. [PubMed:23380522]
  4. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
External Links
KEGG Drug
D10184
PubChem Compound
71768094
PubChem Substance
310265001
ChemSpider
8141643
BindingDB
50400902
ChEBI
76016
ChEMBL
CHEMBL2104993
PharmGKB
PA166122595
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vortioxetine
ATC Codes
N06AX26 — Vortioxetine
AHFS Codes
  • 28:16.04.24 — Serotonin Modulators
FDA label
Download (749 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnTreatmentCoronary Artery Disease / Major Depressive Disorder (MDD)1
1CompletedNot AvailableHealthy Volunteers1
1CompletedOtherHealthy Adult Participants1
1CompletedTreatmentDepression1
1CompletedTreatmentHealthy Men1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentPharmacokinetics1
1CompletedTreatmentSevere Hepatic Impairment1
2CompletedTreatmentAnxiety Disorders / Depressive Disorders1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
2CompletedTreatmentMajor Depressive Disorder (MDD)4
2RecruitingTreatmentBinge Eating Disorder (BED)1
2RecruitingTreatmentBipolar Disorder Depression1
2, 3CompletedTreatmentMajor Depressive Disorder (MDD)1
2, 3Not Yet RecruitingOtherCognitive Change / Major Depressive Disorder (MDD)1
2, 3RecruitingTreatmentAnxiety Disorders / Anxiety States / Cannabis Use Disorders / Depression / Pharmacotherapy1
3Active Not RecruitingTreatmentMajor Depressive Disorder (MDD)1
3CompletedTreatmentGeneralized Anxiety Disorder (GAD)5
3CompletedTreatmentMajor Depressive Disorder (MDD)22
3CompletedTreatmentTreatment Outcomes1
3Enrolling by InvitationTreatmentMajor Depressive Disorder (MDD)2
3RecruitingTreatmentMajor Depressive Disorder (MDD)2
3WithdrawnTreatmentMajor Depressive Disorder (MDD) / Tbi1
4Active Not RecruitingTreatmentMajor Depressive Disorder (MDD)1
4Active Not RecruitingTreatmentMajor Depressive Disorder (MDD) / Social Anxiety Disorder (SAD)1
4CompletedTreatmentDepression / Menopausal Hot Flushes / Menopause / Sleep / Vasomotor Disturbance1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentMajor Depressive Disorder (MDD)2
4CompletedTreatmentPanic Disorders1
4Not Yet RecruitingDiagnosticMajor Depressive Disorder (MDD)1
4Not Yet RecruitingTreatmentMajor Depressive Disorder (MDD) / Type2 Diabetes1
4RecruitingBasic ScienceDepression / Depressive Disorders / Major Depressive Disorder (MDD) / Unipolar Depression1
4RecruitingOtherMajor Depressive Disorder (MDD)1
4RecruitingTreatmentAge-Related Cognitive Decline1
4RecruitingTreatmentMajor Depressive Disorder (MDD)1
4RecruitingTreatmentNegative Symptoms / Schizophrenic Disorders1
4RecruitingTreatmentPost-Traumatic Stress Disorder (PTSD)1
4WithdrawnTreatmentStage I, II or III Breast Cancer / Unipolar Major Depression1
Not AvailableRecruitingNot AvailableMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral5 mg/1
TabletOral10 mg
TabletOral15 mg
TabletOral20 mg
TabletOral5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8476279No2002-10-022022-10-02Us
US7144884No2003-01-092023-01-09Us
US8969355No2007-06-152027-06-15Us
US9227946No2007-06-152027-06-15Us
US8722684No2011-06-302031-06-30Us
US9861630No2007-06-152027-06-15Us
US9125909No2007-06-152027-06-15Us
US9125908No2007-06-152027-06-15Us
US9125910No2007-06-152027-06-15Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00362 mg/mLALOGPS
logP4.51ALOGPS
logP4.76ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area15.27 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity94.01 m3·mol-1ChemAxon
Polarizability34.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
  2. Kamei K, Maeda N, Nomura K, Shibata M, Katsuragi-Ogino R, Koyama M, Nakajima M, Inoue T, Ohno T, Tatsuoka T: Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan. Bioorg Med Chem. 2006 Mar 15;14(6):1978-92. doi: 10.1016/j.bmc.2005.10.046. Epub 2005 Nov 14. [PubMed:16290165]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Ligand
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]
7. solute carrier family 6 member 2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Blocker
References
  1. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [PubMed:21486038]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Chen G, Hojer AM, Areberg J, Nomikos G: Vortioxetine: Clinical Pharmacokinetics and Drug Interactions. Clin Pharmacokinet. 2018 Jun;57(6):673-686. doi: 10.1007/s40262-017-0612-7. [PubMed:29189941]
  3. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65. doi: 10.1124/dmd.112.044610. Epub 2012 Apr 11. [PubMed:22496396]
  2. Brintellix (Vortioxetine) FDA Label [Link]

Drug created on May 12, 2015 11:03 / Updated on October 21, 2018 20:36