Identification

Name
Vilazodone
Accession Number
DB06684
Type
Small Molecule
Groups
Approved
Description

Vilazodone is a novel compound with combined high affinity and selectivity for the 5-hydroxytryptamine (5-HT) transporter and 5-HT(1A) receptors. It has been shown to be equally efficacious as other antidepressants with similar gastrointestinal side effects and possibly with reduced sexual side effects and weight gain. Vilazodone is an antidepressant agent that can used as an alternative for patients who cannot tolerate therapy with other antidepressant classes such as selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors. Treatment should be titrated towards the target dose, which is 40mg per day.

Structure
Thumb
Synonyms
  • Vilazodona
  • Vilazodonum
External IDs
EMD 515259 / EMD-68843 / SB 659746A
Product Ingredients
IngredientUNIICASInChI Key
Vilazodone hydrochlorideU8HTX2GK8J163521-08-2RPZBRGFNBNQSOP-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ViibrydTablet, film coated10 mg/1OralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydTablet10 mgOralForest Laboratories2018-01-31Not applicableCanada
ViibrydTablet20 mg/1OralAllergan, Inc.2011-04-29Not applicableUs00456 1120 30 nlmimage10 123d0918
ViibrydTablet20 mg/1OralCardinal Health2011-04-29Not applicableUs
ViibrydTablet, film coated40 mg/1OralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydTablet40 mgOralForest Laboratories2018-01-31Not applicableCanada
ViibrydTablet10 mg/1OralAllergan, Inc.2011-04-29Not applicableUs
ViibrydTablet10 mg/1OralAvera McKennan Hospital2015-03-03Not applicableUs
ViibrydTablet, film coated20 mg/1OralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydTablet20 mgOralForest Laboratories2018-01-31Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ViibrydVilazodone hydrochloride (10 mg) + Vilazodone hydrochloride (20 mg) + Vilazodone hydrochloride (40 mg)Kit; TabletOralForest LaboratoriesNot applicableNot applicableCanada
ViibrydVilazodone hydrochloride (10 mg) + Vilazodone hydrochloride (20 mg)Kit; TabletOralForest LaboratoriesNot applicableNot applicableCanada
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1)KitOralAllergan, Inc.2011-04-29Not applicableUs
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1) + Vilazodone hydrochloride (40 mg/1)KitOralAllergan, Inc.2011-04-29Not applicableUs
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1) + Vilazodone hydrochloride (40 mg/1)KitOralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1)KitOralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydVilazodone hydrochloride (10 mg) + Vilazodone hydrochloride (20 mg) + Vilazodone hydrochloride (40 mg)Kit; TabletOralForest LaboratoriesNot applicableNot applicableCanada
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1) + Vilazodone hydrochloride (40 mg/1)KitOralAllergan, Inc.2011-04-29Not applicableUs
ViibrydVilazodone hydrochloride (10 mg/1) + Vilazodone hydrochloride (20 mg/1) + Vilazodone hydrochloride (40 mg/1)KitOralTrovis Pharmaceuticals LLC2011-04-182011-04-18Us
ViibrydVilazodone hydrochloride (10 mg) + Vilazodone hydrochloride (20 mg) + Vilazodone hydrochloride (40 mg)Kit; TabletOralForest LaboratoriesNot applicableNot applicableCanada
Categories
UNII
S239O2OOV3
CAS number
163521-12-8
Weight
Average: 441.5249
Monoisotopic: 441.216475133
Chemical Formula
C26H27N5O2
InChI Key
SGEGOXDYSFKCPT-UHFFFAOYSA-N
InChI
InChI=1S/C26H27N5O2/c27-16-18-4-6-23-22(13-18)19(17-29-23)3-1-2-8-30-9-11-31(12-10-30)21-5-7-24-20(14-21)15-25(33-24)26(28)32/h4-7,13-15,17,29H,1-3,8-12H2,(H2,28,32)
IUPAC Name
5-{4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl}-1-benzofuran-2-carboxamide
SMILES
NC(=O)C1=CC2=C(O1)C=CC(=C2)N1CCN(CCCCC2=CNC3=C2C=C(C=C3)C#N)CC1

Pharmacology

Indication

Vilazodone is approved for treatment of acute episodes of major depression. Labeling of vilazodone describes an increased risk of suicidal thoughts in children, adolescents and young adults. The use of vilazodone in pediatrics is not indicated. Its use with monoamine oxidase inhibitors (MAOI) is contraindicated due to increased risk of serotonin syndome. Once the MAOI is discontinued, a 14-day washout period must pass before starting vilazodone.

Associated Conditions
Pharmacodynamics

Vilazodone increases serotonin levels in the brain by inhibiting the reuptake of serotonin while acting as a partial agonist on serotonin-1A receptors. It has therefore been coined by scientists as a selective partial agonist and reuptake inhibitor (SPARI). Because of its partial agonist activity for serotonin-1A, vilazodone helps to reduce anxiety.

Mechanism of action

Since serotonin is believed to be one of the three main neurotransmitters that is low or imbalanced in patients with depression- pathways seeking to increase serotonin levels are targeted by pharmaceutical companies. As a selective serotonin reuptake inhibitor, vilazodone prevents serotonin from re-entering cell bodies. Hence, they will remain longer in the synapse. Vilazodone also has an inherent selectivity for serotonin-1A receptors, acting as a partial agonist which stimulates the production of serotonin. The end result is increased serotonin in the synaptic cleft, allowing serotonin to resume its action on nearby cells. The mechanism of the antidepressant effect of vilazodone is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake.

TargetActionsOrganism
U5-hydroxytryptamine receptor 1A
agonist
Human
Absorption

Vilazodone's absorption is improved when taken with food to 72%.

Volume of distribution
Not Available
Protein binding

96-99% protein bound

Metabolism

Major: CYP3A4. Minor: CYP2C19 and CYP2D6

Route of elimination

1% recovered in urine. 2% unchanged in feces.

Half life

25.4h

Clearance

21.1L/h

Toxicity

Vomiting, serotonin syndrome.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe metabolism of Vilazodone can be decreased when combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbirateroneThe serum concentration of Vilazodone can be increased when it is combined with Abiraterone.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Vilazodone.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Vilazodone.
AceprometazineThe risk or severity of adverse effects can be increased when Vilazodone is combined with Aceprometazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Vilazodone is combined with Acetophenazine.
Acetyl sulfisoxazoleThe serum concentration of Vilazodone can be increased when it is combined with Acetyl sulfisoxazole.
AlaproclateAlaproclate may increase the serotonergic activities of Vilazodone.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Vilazodone.
AlfuzosinThe metabolism of Vilazodone can be decreased when combined with Alfuzosin.
Food Interactions
  • Caution taking vilazodone with foods/herbal product with antiplatelet/anticoagulant properties
  • Gingko bilboa, ginger, garlic, green tea, licorice, horseradish

References

General References
  1. Khan A, Cutler AJ, Kajdasz DK, Gallipoli S, Athanasiou M, Robinson DS, Whalen H, Reed CR: A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry. 2011 Apr;72(4):441-7. doi: 10.4088/JCP.10m06596. [PubMed:21527122]
  2. Traynor K: Vilazodone approved for major depression. Am J Health Syst Pharm. 2011 Mar 1;68(5):366. doi: 10.2146/news110009. [PubMed:21330672]
  3. Howland RH: Vilazodone: another novel atypical antidepressant drug. J Psychosoc Nurs Ment Health Serv. 2011 Mar;49(3):19-22. doi: 10.3928/02793695-20110203-98. Epub 2011 Feb 16. [PubMed:21323263]
  4. Dawson LA, Watson JM: Vilazodone: a 5-HT1A receptor agonist/serotonin transporter inhibitor for the treatment of affective disorders. CNS Neurosci Ther. 2009 Summer;15(2):107-17. [PubMed:19499624]
  5. de Paulis T: Drug evaluation: Vilazodone--a combined SSRI and 5-HT1A partial agonist for the treatment of depression. IDrugs. 2007 Mar;10(3):193-201. [PubMed:17351874]
  6. Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I: Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1220-7. [PubMed:12183683]
  7. Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU: A review of current evidence for vilazodone in major depressive disorder. Int J Psychiatry Clin Pract. 2013 Aug;17(3):160-9. doi: 10.3109/13651501.2013.794245. Epub 2013 May 29. [PubMed:23578403]
  8. Dopheide JA: Vilazodone's comparative merits yet to be demonstrated. Am J Health Syst Pharm. 2012 Sep 15;69(18):1549. doi: 10.2146/ajhp110570. [PubMed:22935936]
External Links
Human Metabolome Database
HMDB0015637
KEGG Drug
D09698
PubChem Compound
6918314
PubChem Substance
175427083
ChemSpider
5293518
BindingDB
50151982
ChEBI
70707
ChEMBL
CHEMBL439849
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vilazodone
ATC Codes
N06AX24 — Vilazodone
AHFS Codes
  • 28:16.04.24 — Serotonin Modulators
FDA label
Download (164 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2CompletedPreventionMemory Disturbances1
2CompletedTreatmentMajor Depressive Disorder (MDD)2
2CompletedTreatmentMarijuana Dependence1
3Active Not RecruitingTreatmentMajor Depressive Disorder (MDD)1
3CompletedTreatmentGeneralized Anxiety Disorder (GAD)2
3CompletedTreatmentMajor Depressive Disorder (MDD)5
3RecruitingTreatmentMajor Depressive Disorder (MDD)1
4CompletedOtherHealthy Controls / Major Depressive Disorder (MDD)1
4CompletedTreatmentDepression / PTSD1
4CompletedTreatmentMajor Depressive Disorder (MDD)4
4CompletedTreatmentSeparation Anxiety Disorder1
4TerminatedTreatmentMajor Depressive Disorder (MDD) / Sexual Dysfunctions1
4WithdrawnTreatmentComorbidity / Feeling Anxious / Major Depressive Disorder (MDD)1
Not AvailableCompletedTreatmentMenopausal Hot Flushes1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableUnknown StatusTreatmentSocial Anxiety Disorder (SAD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitOral
Kit; tabletOral
TabletOral10 mg
TabletOral10 mg/1
TabletOral20 mg
TabletOral20 mg/1
TabletOral40 mg/1
TabletOral40 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral40 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7834020No2002-06-052022-06-05Us
US8193195No2002-06-052022-06-05Us
US8236804No2002-06-052022-06-05Us
US8673921No2002-06-052022-06-05Us
US5532241No1999-09-292019-09-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityAqueous solubility is 0.32 mg/mLNot Available
pKa7.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.123 mg/mLALOGPS
logP4.21ALOGPS
logP3.72ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)14.19ChemAxon
pKa (Strongest Basic)8.6ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area102.29 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity129.71 m3·mol-1ChemAxon
Polarizability50.02 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.9694
Caco-2 permeable-0.6764
P-glycoprotein substrateSubstrate0.6362
P-glycoprotein inhibitor IInhibitor0.581
P-glycoprotein inhibitor IIInhibitor0.9022
Renal organic cation transporterNon-inhibitor0.527
CYP450 2C9 substrateNon-substrate0.9138
CYP450 2D6 substrateNon-substrate0.5431
CYP450 3A4 substrateSubstrate0.5983
CYP450 1A2 substrateNon-inhibitor0.5637
CYP450 2C9 inhibitorInhibitor0.5397
CYP450 2D6 inhibitorNon-inhibitor0.7021
CYP450 2C19 inhibitorInhibitor0.6998
CYP450 3A4 inhibitorNon-inhibitor0.6258
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8731
Ames testNon AMES toxic0.6088
CarcinogenicityNon-carcinogens0.9181
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6208 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8967
hERG inhibition (predictor II)Inhibitor0.87
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
3-alkylindoles / Benzofurans / 2-heteroaryl carboxamides / Furoic acid and derivatives / Dialkylarylamines / N-alkylpiperazines / Aralkylamines / Substituted pyrroles / Benzenoids / Heteroaromatic compounds
show 10 more
Substituents
N-arylpiperazine / 3-alkylindole / Benzofuran / Indole / Indole or derivatives / 2-heteroaryl carboxamide / Furoic acid or derivatives / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aralkylamine
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monocarboxylic acid amide, 1-benzofurans, indoles, nitrile, N-alkylpiperazine (CHEBI:70707)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I: Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1220-7. [PubMed:12183683]
  2. Adamec R, Bartoszyk GD, Burton P: Effects of systemic injections of vilazodone, a selective serotonin reuptake inhibitor and serotonin 1A receptor agonist, on anxiety induced by predator stress in rats. Eur J Pharmacol. 2004 Nov 3;504(1-2):65-77. [PubMed:15507223]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Link [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, Lucki I: Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1220-7. [PubMed:12183683]
  2. Adamec R, Bartoszyk GD, Burton P: Effects of systemic injections of vilazodone, a selective serotonin reuptake inhibitor and serotonin 1A receptor agonist, on anxiety induced by predator stress in rats. Eur J Pharmacol. 2004 Nov 3;504(1-2):65-77. [PubMed:15507223]

Drug created on March 19, 2008 10:49 / Updated on September 21, 2018 00:14