VORTIOXETINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22N2S
Molecular Weight	298.446
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(C)=C(SC2=CC=CC=C2N3CCNCC3)C=C1

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
5-hydroxytryptamine receptor 3A 6 Target ID: P46098 Gene ID: 3359.0 Gene Symbol: HTR3A Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Antagonist 2778	3.7 nM [Ki]
5-hydroxytryptamine receptor 7 15 Target ID: P34969 Gene ID: 3363.0 Gene Symbol: HTR7 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Antagonist 2778	19.0 nM [Ki]
5-hydroxytryptamine receptor 1D 17 Target ID: P28221 Gene ID: 3352.0 Gene Symbol: HTR1D Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Antagonist 2778	54.0 nM [Ki]
5-hydroxytryptamine receptor 1B 21 Target ID: P28222 Gene ID: 3351.0 Gene Symbol: HTR1B Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Antagonist 2778	33.0 nM [Ki]
5-hydroxytryptamine receptor 1A 54 Target ID: P08908 Gene ID: 3350.0 Gene Symbol: HTR1A Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Antagonist 2778	15.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 173 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204447s011lbl.pdf	Primary		Approved 8429	BRINTELLIX Approved Use Indicated for the treatment of major depressive disorder (MDD). Launch Date 2013

C_max

Value	Dose	Analyte	Population
17.92 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29189941/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/29189941/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/204447s013lbl.pdf	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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

Value	Dose	Analyte	Population
344 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29189941/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/29189941/	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02170220	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:

T_1/2

Value	Dose	Analyte	Population
58.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29189941/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/29189941/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/204447s013lbl.pdf	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

F_unbound

Value	Dose	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29189941/	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% REVIEW https://pubmed.ncbi.nlm.nih.gov/29189941/	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% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/204447s013lbl.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/22448783	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: https://pubmed.ncbi.nlm.nih.gov/22448783	Sources: https://pubmed.ncbi.nlm.nih.gov/22448783
75 mg single, oral Highest studied dose Dose: 75 mg Route: oral Route: single Dose: 75 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22448783	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: https://pubmed.ncbi.nlm.nih.gov/22448783	Sources: https://pubmed.ncbi.nlm.nih.gov/22448783
9 mg single, intravenous Dose: 9 mg Route: intravenous Route: single Dose: 9 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22448783	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: https://pubmed.ncbi.nlm.nih.gov/22448783	Sources: https://pubmed.ncbi.nlm.nih.gov/22448783
250 mg single, oral Overdose Dose: 250 mg Route: oral Route: single Dose: 250 mg Co-administed with:: clonazepam(10 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/29923970	unhealthy, 50 years n = 1 Health Status: unhealthy Condition: major depressive disorder Age Group: 50 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29923970	Other AEs: Suicide attempt... Other AEs: Suicide attempt Sources: https://pubmed.ncbi.nlm.nih.gov/29923970
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf	Disc. AE: Nausea... Other AEs: Suicidal ideation, Suicidal behavior... AEs leading to discontinuation/dose reduction: Nausea Other AEs: Suicidal ideation Suicidal behavior Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97	Disc. AE: Reaction skin, Vomiting... AEs leading to discontinuation/dose reduction: Reaction skin Vomiting Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97

AEs

AE	Significance	Dose	Population
Suicide attempt		250 mg single, oral Overdose Dose: 250 mg Route: oral Route: single Dose: 250 mg Co-administed with:: clonazepam(10 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/29923970	unhealthy, 50 years n = 1 Health Status: unhealthy Condition: major depressive disorder Age Group: 50 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29923970
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97	unhealthy, adult Health Status: unhealthy Condition: major depressive disorder Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000MedR.pdf Page: p. 97

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037 inducer 389 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2E1 882 CYP3A4/5 278 CYP2C8 911 BCRP 699 BSEP 402 MATE1 306 MATE2 263 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647	P-gp 1537 CYP3A4/5 85 CYP2C19 991 CYP2A6 543 CYP2C8 693 CYP2B6 664	CYP1A2 701 CYP2A6 79 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	moderate [IC50 4.4 uM]	no (co-administration study) Comment: no dose adjustment needed for vortioxetine coadministration with digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no [IC50 >34 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no [IC50 >34 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no [IC50 >34 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no [IC50 >34 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 76.0	no [IC50 >34 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 76.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204447s017lbl.pdf Page: 13.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	yes [Ki 15 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	yes [Ki 9.34 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 45, 47, 48, 56	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 45, 47, 48, 56
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 27.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56	yes
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80	yes	unlikely (co-administration study) Comment: no dose adjustment need with CYP2B6 substrate e.g. bupropion Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80	yes	unlikely (co-administration study) Comment: no dose adjustment need with CYP2C19 substrate e.g. diazepam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80	yes	unlikely (co-administration study) Comment: no dose adjustment need with CYP2C9 substrate e.g. S-warfarin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80	yes	unlikely (co-administration study) Comment: no dose adjustment need with CYP3A substrate e.g. midazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000ClinPharmR.pdf Page: 48, 56, 80

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204447Orig1s000PharmR.pdf Page: 20, 145

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	NO15845	https://www.001chemical.com/chem/508233-74-7
AA Blocks	AA00DB50	https://www.aablocks.com/goods/Goods/detail?id=AA00DB50
AEchem Scientific Corp., USA	AE1-013736	http://www.aechemsc.com/info_products/AE1-013736.php
AK Scientific, Inc. (AKSCI)	7034AB	http://www.aksci.com/item_detail.php?cat=7034AB
Aaron Chemicals	AR00DBWS	http://www.aaronchem.com/508233-74-7
AbMole Bioscience	M6058	http://www.abmole.com/products/vortioxetine.html
Acadechem	ACDS-056587	http://www.acadechemical.com/product/131286
Achemo Scientific Limited	AC-78836	http://www.achemo.com/search/?Keyword= 508233-74-7
Achemtek	0102-013931	http://www.achemtek.com/508233-74-7
Acorn PharmaTech	ACN-036290	http://www.acornpharmatech.com/
Alsachim	3603	http://www.alsachim.com/product-C4887-glo.bal-view.html
Ambinter	Amb21926577	http://www.ambinter.com/reference/21926577
Angel Pharmatech	AG-26242	http://www.angelpharmatech.com/508233-74-7.html
Ansion Pharma	508233-74-7	http://www.ansionpharma.com/English/Product/1870421349.html
ApexBio Technology	A3926	http://www.apexbt.com/vortioxetine.html
Ark Pharm	AK110506	http://www.arkpharminc.com/products/508233-74-7.html
Ark Pharma Scientific Limited	H-009279	http://www.arkpharmtech.com/product/14334.html
Aurora Fine Chemicals LLC	A13.110.975	http://online.aurorafinechemicals.com/info?ID=A13.110.975
Aurum Pharmatech LLC	W-5909	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5909
AvaChem Scientific	3380	http://www.avachem.com/productSearch.asp?3380
BioChemPartner	BCP05996	http://www.biochempartner.com/508233-74-7-BCP05996
BioCrick	BCC2046	http://www.biocrick.com/Vortioxetine-BCC2046.html
Chem Scene	CS-1471	http://www.chemscene.com/508233-74-7.html
Chemspace	CSSB00020618850	https://chem-space.com/CSSB00020618850
DC Chemicals	DC8613	http://www.dcchemicals.com/product_show-Vortioxetine_Lu_AA21004_.html
Debye Scientific	DA-42264	http://www.debyesci.com/cas_508233-74-7.html
Finetech	FT-0686961	http://www.finetechnology-ind.com/prod/detail/pub/508233-74-7.html
Fragmenta	PIP107	http://www.fragmenta.com/productDetails.asp?cellC=++style%3D%27background%3A%23E8F8FF%3B+color%3A%23fff%3B%27+&productID=PIP107
Hairui	HR118576	http://www.hairuichem.com/en/product/508233-74-7.html
Hefei Hirisun Pharmatech Co., Ltd	HR010072	http://www.hirisunpharm.com/508233-74-7.html
LGC Standards	LGCFOR3264.00	https://www.lgcstandards.com/US/en/p/LGCFOR3264.00
LGC Standards	MM3264.00	https://www.lgcstandards.com/US/en/p/MM3264.00
Lab Network	LN00201852	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00201852
Matrix Scientific	98153	https://www.matrixscientific.com/098153.html
MedChem Express	HY-15414	https://www.medchemexpress.com/Vortioxetine.html
Molcore	CS15845	https://www.molcore.com/product/508233-74-7
Sinfoo Biotech	S040930	http://www.sinfoobiotech.com/product/1044328
Smolecule	S546869	http://www.smolecule.com/products/s546869
Specs	AR-270/43507985	http://www.specs.net/enter.php?specsid=AR-270/43507985
Synblock Inc	SB16506	http://www.synblock.com/product/508233-74-7.html
THE BioTek	bt-286496	https://www.thebiotek.com/product/inhibitors/bt-286496
THE BioTek	bt-464311	https://www.thebiotek.com/product/others/bt-464311
Vitas-M Laboratory	STL483777	http://www.request.vitasmlab.com/index.php?option=com_search_stk&Itemid=22&stk=STL483777&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
abcr GmbH	AB459995	http://www.abcr.de/shop/en/AB459995
eNovation Chemicals	D541250	http://www.enovationchem.com/productDetails.asp?productID=D541250
iChemical	EBD555355	http://www.ichemical.com/products/508233-74-7.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
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	21486038

Patents

Sample Use Guides

In Vivo Use Guide

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

Name

Type

Language

VORTIOXETINE

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

Vortioxetine [WHO-DD]

Common Name

English

LUAA21004

Code

English

vortioxetine [INN]

Common Name

English

VORTIOXETINE [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N06AX26