U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H22N2S
Molecular Weight 298.4474
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VORTIOXETINE

SMILES

Cc1ccc(c(C)c1)Sc2ccccc2N3CCNCC3

InChI

InChIKey=YQNWZWMKLDQSAC-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C18H22N2S
Molecular Weight 298.4474
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=15341484; http://www.ncbi.nlm.nih.gov/pubmed/?term=21486038

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

CNS Activity

Curator's Comment:: Vortioxetine is a SSRI that binds to the presynaptic serotonin reuptake site, increasing the level of serotonin (5-HT) in the neuronal synapse, as well as selectively binding to a variety of other serotonin receptors, thus enhancing CNS serotonergic activity.

Originator

Curator's Comment:: Trintellix (vortioxetine) was discovered by Lundbeck researchers in Copenhagen, Denmark. The clinical trial program in the United States was conducted jointly by Lundbeck and Takeda, and Takeda holds the new drug application for the U.S. market. Trintellix is a trademark of H. Lundbeck A/S and used under license by Takeda Pharmaceuticals America, Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P46098
Gene ID: 3359.0
Gene Symbol: HTR3A
Target Organism: Homo sapiens (Human)
3.7 nM [Ki]
Target ID: P34969
Gene ID: 3363.0
Gene Symbol: HTR7
Target Organism: Homo sapiens (Human)
19.0 nM [Ki]
Target ID: P28221
Gene ID: 3352.0
Gene Symbol: HTR1D
Target Organism: Homo sapiens (Human)
54.0 nM [Ki]
Target ID: P28222
Gene ID: 3351.0
Gene Symbol: HTR1B
Target Organism: Homo sapiens (Human)
33.0 nM [Ki]
Target ID: P08908
Gene ID: 3350.0
Gene Symbol: HTR1A
Target Organism: Homo sapiens (Human)
15.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BRINTELLIX

Approved Use

Indicated for the treatment of major depressive disorder (MDD).

Launch Date

1.38049919E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
17.92 ng/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.6 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
33 ng/mL
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.374 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
2.654 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
0.008 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA39835 plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
0.0289999999999999 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA39835 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
1.67 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
2.078 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
344 ng × h/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
273.42 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
71.942 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
88.614 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
122.899 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
124.708 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA34443 plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
0.078 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA39835 plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
1.143 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
LU-AA39835 plasma
Homo sapiens
population: healthy
age:
sex:
food status:
166.955 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
188.662999999999 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
187.202 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: healthy
age:
sex:
food status:
288.053 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
58.84 h
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
60.62 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
66 h
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2%
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VORTIOXETINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg 1 times / day steady, oral
Highest studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
healthy, 24 years(range: 18–53) years.
n = 5
Health Status: healthy
Age Group: 24 years(range: 18–53) years.
Sex: M
Population Size: 5
Sources:
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, 24 years(range: 18–53) years.
n = 6
Health Status: healthy
Age Group: 24 years(range: 18–53) years.
Sex: M+F
Population Size: 6
Sources:
9 mg single, intravenous
Dose: 9 mg
Route: intravenous
Route: single
Dose: 9 mg
Sources:
healthy, 24 years(range: 18–53) years.
n = 22
Health Status: healthy
Age Group: 24 years(range: 18–53) years.
Sex: M+F
Population Size: 22
Sources:
250 mg single, oral
Overdose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Co-administed with::
clonazepam(10 mg)
Sources:
unhealthy, 50 years
n = 1
Health Status: unhealthy
Condition: major depressive disorder
Age Group: 50 years
Sex: M
Population Size: 1
Sources:
Other AEs: Suicide attempt...
Other AEs:
Suicide attempt
Sources:
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources:
Disc. AE: Nausea...
Other AEs: Suicidal ideation, Suicidal behavior...
AEs leading to
discontinuation/dose reduction:
Nausea
Other AEs:
Suicidal ideation
Suicidal behavior
Sources:
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources: Page: p. 97
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources: Page: p. 97
Disc. AE: Reaction skin, Vomiting...
AEs leading to
discontinuation/dose reduction:
Reaction skin
Vomiting
Sources: Page: p. 97
AEs

AEs

AESignificanceDosePopulation
Suicide attempt
250 mg single, oral
Overdose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Co-administed with::
clonazepam(10 mg)
Sources:
unhealthy, 50 years
n = 1
Health Status: unhealthy
Condition: major depressive disorder
Age Group: 50 years
Sex: M
Population Size: 1
Sources:
Suicidal behavior
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources:
Suicidal ideation
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources:
Nausea Disc. AE
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources:
Reaction skin Disc. AE
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources: Page: p. 97
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources: Page: p. 97
Vomiting Disc. AE
20 mg 1 times / day steady, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Sources: Page: p. 97
unhealthy, adult
Health Status: unhealthy
Condition: major depressive disorder
Age Group: adult
Sources: Page: p. 97
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [IC50 4.4 uM]
no (co-administration study)
Comment: no dose adjustment needed for vortioxetine coadministration with digoxin
Page: 27.0
no [IC50 >34 uM]
no [IC50 >34 uM]
no [IC50 >34 uM]
no [IC50 >34 uM]
no [IC50 >34 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [Ki 15 uM]
yes [Ki 9.34 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
likely (co-administration study)
Comment: dose decrease may be needed with CYP2D6 inhibitor such as bupropion, dose should be increased by 3 fold when administered with strong CYP inducer such as rifampacin
Page: 45, 47, 48, 56
no
yes
yes
yes
unlikely (co-administration study)
Comment: no dose adjustment need with CYP2B6 substrate e.g. bupropion
Page: 48, 56, 80
yes
unlikely (co-administration study)
Comment: no dose adjustment need with CYP2C19 substrate e.g. diazepam
Page: 48, 56, 80
yes
unlikely (co-administration study)
Comment: no dose adjustment need with CYP2C9 substrate e.g. S-warfarin
Page: 48, 56, 80
yes
unlikely (co-administration study)
Comment: no dose adjustment need with CYP3A substrate e.g. midazolam
Page: 48, 56, 80
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Synthesis and structure--activity relationship in a class of indolebutylpiperazines as dual 5-HT(1A) receptor agonists and serotonin reuptake inhibitors.
2004 Sep 9
Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder.
2011 May 12
Patents

Sample Use Guides

The recommended starting dose is 10 mg administered orally once daily without regard to meals. The dose should then be increased to 20 mg/day, as tolerated. Consider 5 mg/day for patients who do not tolerate higher doses. TRINTELLIX can be discontinued abruptly. However, it is recommended that doses of 15 mg/day or 20 mg/day be reduced to 10 mg/day for one week prior to full discontinuation if possible. The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:17:51 UTC 2021
Edited
by admin
on Fri Jun 25 23:17:51 UTC 2021
Record UNII
3O2K1S3WQV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VORTIOXETINE
DASH   INN   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
LU-AA21004
Code English
LU AA21004
Code English
VORTIOXETINE [USAN]
Common Name English
PIPERAZINE, 1-(2-((2,4-DIMETHYLPHENYL)THIO)PHENYL)-
Systematic Name English
VORTIOXETINE [MI]
Common Name English
1-(2-((2,4-DIMETHYLPHENYL)SULFANYL)PHENYL)PIPERAZINE
Systematic Name English
LUAA21004
Code English
VORTIOXETINE [WHO-DD]
Common Name English
VORTIOXETINE [INN]
Common Name English
VORTIOXETINE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-ATC N06AX26
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
WHO-VATC QN06AX26
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
NCI_THESAURUS C265
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
Code System Code Type Description
DRUG CENTRAL
4806
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
FDA UNII
3O2K1S3WQV
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
RXCUI
1455099
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY RxNorm
HSDB
8250
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
EVMPD
SUB88928
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
LACTMED
Vortioxetine
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
NCI_THESAURUS
C152917
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
INN
9279
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
MERCK INDEX
M11708
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
CAS
508233-74-7
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
ChEMBL
CHEMBL2104993
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
IUPHAR
7351
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
DRUG BANK
DB09068
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
WIKIPEDIA
VORTIOXETINE
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
PUBCHEM
9966051
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
MESH
C557874
Created by admin on Fri Jun 25 23:17:51 UTC 2021 , Edited by admin on Fri Jun 25 23:17:51 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> AGONIST
SHORT-ACTING
TARGET -> AGONIST
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
Major Enzyme for this transformation
MINOR
PLASMA
METABOLITE -> PARENT
Minor Enzyme for this transformation
MINOR
PLASMA
METABOLITE -> PARENT
MINOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC