Details of the Drug

General Information of Drug (ID: DM6F1PU)

Drug Name

Vortioxetine

Synonyms

VORTIOXETINE; 508233-74-7; 1-(2-((2,4-Dimethylphenyl)thio)phenyl)piperazine; Lu AA21004; UNII-3O2K1S3WQV; 3O2K1S3WQV; CHEBI:76016; Trintellix; 1-{2-[(2,4-dimethylphenyl)sulfanyl]phenyl}piperazine; Piperazine, 1-[2-[(2,4-dimethylphenyl)thio]phenyl]-; Brintellix (TN); 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine; 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine; 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine; CHEMBL2204360; 1-[2-[(2,4-Dimethylphenyl)thio]phenyl]piperazine; Lu-AA21004

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[1]
Mood disorder	6A60-6E23	Phase 3	[2]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

298.4

Logarithm of the Partition Coefficient (xlogp)

4.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 5.8 mL/min/kg [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 66 hours [3]
Metabolism: The drug is metabolized via the cytochrome P450 isozymes []
Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [3]
Vd: The volume of distribution (Vd) of drug is 2600 L []

Chemical Identifiers

Formula: C18H22N2S
IUPAC Name: 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine
Canonical SMILES: CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C
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
InChIKey: YQNWZWMKLDQSAC-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 9966051
ChEBI ID: CHEBI:76016
CAS Number: 508233-74-7
DrugBank ID: DB09068
TTD ID: D03WEX
VARIDT ID: DR01102
INTEDE ID: DR1712
ACDINA ID: D00735

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[5]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[6]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[5]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[5]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Protein Interaction/Cellular Processes	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Major depressive disorder

ICD Disease Classification

6A70.3

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	5.57E-01	-7.89E-02	-7.93E-01
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	4.32E-01	4.39E-02	4.30E-01
Cytochrome P450 2A6 (CYP2A6)	DME	CYP2A6	8.99E-01	4.59E-03	2.19E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.57E-01	9.43E-03	1.29E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	9.62E-01	2.57E-02	1.10E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.35E-01	2.78E-02	2.09E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Vortioxetine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Vortioxetine and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[8]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Vortioxetine caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Vortioxetine caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Oliceridine	DM6MDCF	Moderate	Additive serotonergic effects by the combination of Vortioxetine and Oliceridine.	Acute pain [MG31]	[10]
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Inotersen.	Amyloidosis [5D00]	[11]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Vortioxetine caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Vortioxetine caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[9]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Vortioxetine and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[12]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Tazemetostat.	Follicular lymphoma [2A80]	[11]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[11]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Vortioxetine caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[13]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Vortioxetine caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[14]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Vortioxetine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[15]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Vortioxetine caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Dacomitinib	DMOH8VY	Major	Decreased metabolism of Vortioxetine caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[9]
Acalabrutinib	DM7GCVW	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[11]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Vortioxetine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[16]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Vortioxetine and Ozanimod.	Multiple sclerosis [8A40]	[17]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Vortioxetine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[18]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of Vortioxetine caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[19]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[11]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Vortioxetine and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[20]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Vortioxetine caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Betrixaban.	Venous thromboembolism [BD72]	[11]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Vortioxetine 15 mg tablet	15 mg	Oral Tablet	Oral
Vortioxetine 10 mg tablet	10 mg	Oral Tablet	Oral
Vortioxetine 20 mg tablet	20 mg	Oral Tablet	Oral
Vortioxetine 5 mg tablet	5 mg	Oral Tablet	Oral
Vortioxetine Hydrobromide eq 15mg base tablet	eq 15mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 10mg base tablet	eq 10mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 5mg base tablet	eq 5mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 20mg base tablet	eq 20mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7351).
2	Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav. 2013 Apr;105:41-50.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
5	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.
6	Vortioxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2018 Jun;57(6):673-686.
7	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.
8	Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
9	Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL.
10	Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
11	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
12	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
13	Product Information. Givlaari (givosiran). Alnylam Pharmaceuticals, Cambridge, MA.
14	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
15	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
16	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
17	Alvine G, Black DW, Tsuang D "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry 51 (1990): 311. [PMID: 2365671]
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
20	Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7. [PMID: 11678792]