Identification

Name
Iloperidone
Accession Number
DB04946
Type
Small Molecule
Groups
Approved
Description

Iloperidone is an atypical antipsychotic for the treatment of schizophrenia symptoms. Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights to Titan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals announced that the Phase III development rights have been acquired by Vanda Pharmaceuticals. FDA approved on May 9, 2009.

Structure
Thumb
Synonyms
  • 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone
  • 4'-(3-(4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino)propoxy)-3'-methoxyacetophenone
  • Fanapta
  • Iloperidona
  • Iloperidone
  • Iloperidonum
  • Zomaril
External IDs
HP 873 / HP-873
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FanaptTablet6 mg/1OralVanda Pharmaceuticals Inc.2016-07-01Not applicableUs
FanaptTablet12 mg/1OralNovartis2009-10-012017-08-31Us
FanaptTablet1 mg/1OralNovartis2009-10-012017-08-31Us
FanaptTablet4 mg/1OralAvera McKennan Hospital2016-07-01Not applicableUs
FanaptTablet4 mg/1OralNovartis2009-10-012017-08-31Us00078 0597 20 nlmimage10 cd45e6af
FanaptTablet8 mg/1OralVanda Pharmaceuticals Inc.2015-09-15Not applicableUs
FanaptTablet8 mg/1OralNovartis2009-10-012017-08-31Us00078 0599 20 nlmimage10 6e3db77d
FanaptTablet10 mg/1OralVanda Pharmaceuticals Inc.2016-01-15Not applicableUs
FanaptTablet2 mg/1OralVanda Pharmaceuticals Inc.2016-08-01Not applicableUs
FanaptTablet2 mg/1OralNovartis2009-10-012017-08-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IloperidoneTablet1 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet12 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet4 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet8 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet2 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet6 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
IloperidoneTablet10 mg/1OralMylan Pharmaceuticals2017-03-20Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralNovartis2009-10-012017-08-31Us
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2015-12-01Not applicableUs
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2018-09-24Not applicableUs
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralNovartis2009-10-012017-08-31Us
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2015-12-01Not applicableUs
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2018-09-24Not applicableUs
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralNovartis2009-10-012017-08-31Us
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2015-12-01Not applicableUs
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralNovartis2009-10-012017-08-31Us
FanaptIloperidone (1 mg/1) + Iloperidone (2 mg/1) + Iloperidone (4 mg/1) + Iloperidone (6 mg/1)KitOralVanda Pharmaceuticals Inc.2018-09-24Not applicableUs
International/Other Brands
Fanapt / Fiapta / Zomaril
Categories
UNII
VPO7KJ050N
CAS number
133454-47-4
Weight
Average: 426.4806
Monoisotopic: 426.195485567
Chemical Formula
C24H27FN2O4
InChI Key
XMXHEBAFVSFQEX-UHFFFAOYSA-N
InChI
InChI=1S/C24H27FN2O4/c1-16(28)18-4-7-21(23(14-18)29-2)30-13-3-10-27-11-8-17(9-12-27)24-20-6-5-19(25)15-22(20)31-26-24/h4-7,14-15,17H,3,8-13H2,1-2H3
IUPAC Name
1-(4-{3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy}-3-methoxyphenyl)ethan-1-one
SMILES
COC1=C(OCCCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C=CC(=C1)C(C)=O

Pharmacology

Indication

Treatment of acute schizophrenia.

Associated Conditions
Pharmacodynamics

Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors.

Mechanism of action

Iloperidone is a dopamine D2 and 5-HT2A receptor antagonist and acts as a neuroleptic agent.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Human
AD(2) dopamine receptor
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
UD(4) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
U5-hydroxytryptamine receptor 6
antagonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UHistamine H1 receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
Absorption

Well absorbed from the GI tract and Cmax is reached within 2-4 hours. Steady-state concentration is achieved in 3-4 days post-administration of iloperidone. Relative bioavailability of the tablet formulation compared to oral solution is 96%. Accumulation occurs in a predictable fashion.

Volume of distribution

Apparent Vd = 1340-2800 L

Protein binding

95% of iloperidone is bound to protein. Percent bound is not altered by renal or hepatic impairment or combination therapy with ketoconazole.

Metabolism

Iloperidone is hepatically metabolized by cytochrome enzymes which mediates O-dealkylation (CYP3A4), hydroxylation (CYP2D6), and decarboxylation/reduction processes. Metabolites formed are P89, P95, and P88. The minor metabolite is P89, whereas P95 and P88 are the major ones. The affinity of the iloperidone metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEα1A, NEα1B, NEα1D, and NEα2C receptors (Ki values of 4.7, 2.7, 8.8 and 4.7 nM respectively).

Route of elimination

Renal (in which <1% of iloperidone is excreted unchanged).

Half life

The observed mean elimination half-lives for iloperidone, P88 and P95 in CYP2D6 extensive metabolizers (EM) are 18, 26 and 23 hours, respectively, and in poor metabolizers (PM) are 33, 37 and 31 hours, respectively.

Clearance

Apparent clearance (clearance/bioavilability) = 47-102 L/h.

Toxicity

Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

Affected organisms
  • Humans and other mammals
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 dose requirement.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.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 dose requirement.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Iloperidone is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Iloperidone is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid is combined with Iloperidone.
1-benzylimidazoleThe risk or severity of hypertension can be increased when 1-benzylimidazole is combined with Iloperidone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Iloperidone.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Iloperidone.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Iloperidone 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 Iloperidone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Iloperidone.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Iloperidone.
Food Interactions
  • Administration of iloperidone with a standard high-fat meal did not significantly affect the Cmax or AUC of iloperidone, P88, or P95, but delayed Tmax by 1 hour for iloperidone, 2 hours for P88 and 6 hours for P95.
  • Can be taken with or without meals

References

Synthesis Reference
US5364866
General References
  1. Strupczewski JT, Bordeau KJ, Chiang Y, Glamkowski EJ, Conway PG, Corbett R, Hartman HB, Szewczak MR, Wilmot CA, Helsley GC: 3-[[(Aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles as D2/5-HT2 antagonists with potential atypical antipsychotic activity: antipsychotic profile of iloperidone (HP 873). J Med Chem. 1995 Mar 31;38(7):1119-31. [PubMed:7707315]
  2. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [PubMed:8997630]
  3. Hesselink JM: Iloperidone (Novartis). IDrugs. 2002 Jan;5(1):84-90. [PubMed:12861482]
  4. Hesselink JM: Iloperidone (Hoechst Marion Roussel Inc). IDrugs. 1999 Jun;2(6):584-90. [PubMed:16127622]
  5. Szewczak MR, Corbett R, Rush DK, Wilmot CA, Conway PG, Strupczewski JT, Cornfeldt M: The pharmacological profile of iloperidone, a novel atypical antipsychotic agent. J Pharmacol Exp Ther. 1995 Sep;274(3):1404-13. [PubMed:7562515]
  6. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
  7. Citrome L: Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1551-64. doi: 10.1517/17425255.2010.531259. Epub 2010 Nov 1. [PubMed:21034370]
External Links
KEGG Drug
D02666
PubChem Compound
71360
PubChem Substance
175426913
ChemSpider
64459
BindingDB
50034043
ChEBI
65173
ChEMBL
CHEMBL14376
PharmGKB
PA161199368
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Iloperidone
ATC Codes
N05AX14 — Iloperidone
FDA label
Download (352 KB)
MSDS
Download (480 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentBioequivalence1
1CompletedNot AvailableHepatic Impairment1
1CompletedTreatmentSafety and Tolerability of Iloperidone1
1, 2CompletedTreatmentSchizophrenic Disorders1
2CompletedTreatmentEfficacy / Iloperidone / Schizophrenic Disorders1
2CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
3CompletedTreatmentSchizophrenic Disorders2
3RecruitingTreatmentSchizophrenic Disorders1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentSchizophrenic Disorders1
4TerminatedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitOral
TabletOral1 mg/1
TabletOral10 mg/1
TabletOral12 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral6 mg/1
TabletOral8 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE39198No2006-07-182016-11-15Us
US8586610No2013-11-192027-11-02Us
US9074255No2015-07-072030-12-17Us
US9072742No2015-07-072031-01-16Us
US9074256No2015-07-072031-02-10Us
US9157121No2015-10-132030-04-05Us
US9138432No2015-09-222025-09-30Us
US8999638No2015-04-072030-10-28Us
US9074254No2015-07-072031-12-28Us
US8652776No2014-02-182030-08-31Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.0304 mg/mLALOGPS
logP4.26ALOGPS
logP3.22ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)16.14ChemAxon
pKa (Strongest Basic)7.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area64.8 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity116.65 m3·mol-1ChemAxon
Polarizability46.51 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9848
Caco-2 permeable+0.5513
P-glycoprotein substrateSubstrate0.6668
P-glycoprotein inhibitor IInhibitor0.8242
P-glycoprotein inhibitor IIInhibitor0.9268
Renal organic cation transporterInhibitor0.5726
CYP450 2C9 substrateNon-substrate0.9051
CYP450 2D6 substrateSubstrate0.892
CYP450 3A4 substrateSubstrate0.7409
CYP450 1A2 substrateNon-inhibitor0.6111
CYP450 2C9 inhibitorNon-inhibitor0.5061
CYP450 2D6 inhibitorNon-inhibitor0.886
CYP450 2C19 inhibitorInhibitor0.6257
CYP450 3A4 inhibitorInhibitor0.6777
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9008
Ames testNon AMES toxic0.6314
CarcinogenicityNon-carcinogens0.8699
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7862 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6563
hERG inhibition (predictor II)Inhibitor0.7945
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 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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0059-1591700000-642ca68996469c31b6b8

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Alkyl-phenylketones
Alternative Parents
Acetophenones / Benzisoxazoles / Phenoxy compounds / Anisoles / Methoxybenzenes / Benzoyl derivatives / Aryl alkyl ketones / Alkyl aryl ethers / Aralkylamines / Piperidines
show 10 more
Substituents
Alkyl-phenylketone / Acetophenone / Benzisoxazole / Phenoxy compound / Anisole / Benzoyl / Phenol ether / Aryl alkyl ketone / Methoxybenzene / Alkyl aryl ether
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, organofluorine compound, tertiary amino compound, aromatic ether, methyl ketone, aromatic ketone, monoamine, 1,2-benzoxazoles (CHEBI:65173)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [PubMed:8997630]
  2. Hesselink JM: Iloperidone (Novartis). IDrugs. 2002 Jan;5(1):84-90. [PubMed:12861482]
Details
2. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [PubMed:8997630]
  2. Hesselink JM: Iloperidone (Novartis). IDrugs. 2002 Jan;5(1):84-90. [PubMed:12861482]
Details
3. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Details
10. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Bobo WV: Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. [PubMed:23272794]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Mutlib AE, Klein JT: Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93. [PubMed:9732390]
  2. Citrome L: Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1551-64. doi: 10.1517/17425255.2010.531259. Epub 2010 Nov 1. [PubMed:21034370]
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. Mutlib AE, Klein JT: Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93. [PubMed:9732390]
  2. Citrome L: Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1551-64. doi: 10.1517/17425255.2010.531259. Epub 2010 Nov 1. [PubMed:21034370]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Mutlib AE, Klein JT: Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93. [PubMed:9732390]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Mutlib AE, Klein JT: Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93. [PubMed:9732390]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Mutlib AE, Klein JT: Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther. 1998 Sep;286(3):1285-93. [PubMed:9732390]

Drug created on October 21, 2007 16:23 / Updated on December 14, 2018 17:10