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Details

Stereochemistry ACHIRAL
Molecular Formula C24H27FN2O4
Molecular Weight 426.4806
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ILOPERIDONE

SMILES

COC1=CC(=CC=C1OCCCN2CCC(CC2)C3=NOC4=C3C=CC(F)=C4)C(C)=O

InChI

InChIKey=XMXHEBAFVSFQEX-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C24H27FN2O4
Molecular Weight 426.4806
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Iloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia. 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. Iloperidone is indicated for the treatment of acute schizophrenia.

CNS Activity

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FANAPT
PubMed

PubMed

TitleDatePubMed
The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs.
1989
3-[[(Aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles as D2/5-HT2 antagonists with potential atypical antipsychotic activity: antipsychotic profile of iloperidone (HP 873).
1995 Mar 31
The pharmacological profile of iloperidone, a novel atypical antipsychotic agent.
1995 Sep
Iloperidone binding to human and rat dopamine and 5-HT receptors.
1996 Dec 19
Iloperidone (Hoechst Marion Roussel Inc).
1999 Jun
Treatments for chronic psychosis.
2001 Dec
Iloperidone (Novartis).
2002 Jan
Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: an in vitro study.
2003
Functional characterization of the novel antipsychotic iloperidone at human D2, D3, alpha 2C, 5-HT6, and 5-HT1A receptors.
2003 Jul 18
Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm.
2003 Sep
Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions.
2004 Feb
Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats.
2006 Sep
Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability.
2008
Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies.
2008 Apr
Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia.
2008 Apr
Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia.
2008 Apr
Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials.
2008 Apr
New advances in the treatment of schizophrenia. Introduction.
2008 Apr
Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market?
2008 Jan
Gateways to clinical trials. July-August 2008.
2008 Jul-Aug
American psychiatric association.
2008 Jun
Effect of a ciliary neurotrophic factor polymorphism on schizophrenia symptom improvement in an iloperidone clinical trial.
2008 Mar
Gateways to clinical trials.
2008 Oct
Further characterization of the discriminative stimulus properties of the atypical antipsychotic drug clozapine in C57BL/6 mice: role of 5-HT(2A) serotonergic and alpha (1) adrenergic antagonism.
2009 Apr
Genome-wide association studies in pharmacogenomics: untapped potential for translation.
2009 Apr 28
Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychotic.
2009 Aug
Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study.
2009 Aug
Iloperidone: a new option for the treatment of schizophrenia.
2009 Dec
Pharmacogenomics: the promise of personalized medicine for CNS disorders.
2009 Jan
Applicability of a genetic signature for enhanced iloperidone efficacy in the treatment of schizophrenia.
2009 Jun
Akathisia and second-generation antipsychotic drugs.
2009 May
Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia.
2009 Nov
Iloperidone: in schizophrenia.
2009 Oct
Iloperidone for the treatment of schizophrenia.
2010 Aug
Iloperidone for schizophrenia.
2010 Aug
A review of new atypical antipsychotic launches in the United States.
2010 Dec
Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion.
2010 Dec
New atypical antipsychotics for schizophrenia: iloperidone.
2010 Feb 18
Iloperidone (Fanapt)--another second-generation antipsychotic.
2010 Feb 22
Absence of weight gain association with the HTR2C -759C/T polymorphism in patients with schizophrenia treated with iloperidone.
2010 Feb 28
Gateways to clinical trials.
2010 Jan-Feb
New drugs: asenapine, iloperidone, and bepotastine besilate.
2010 Jan-Feb
Atypical antipsychotic metabolism and excretion.
2010 Jul
Iloperidone for the treatment of schizophrenia.
2010 May
Iloperidone redux: a dissection of the Drug Approval Package for this newly commercialised second-generation antipsychotic.
2010 May
The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis.
2010 Oct
New antipsychotic drugs: how do their receptor-binding profiles compare?
2010 Sep
Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults.
2013 Jan
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013 Nov
Patents

Sample Use Guides

In Vivo Use Guide
The recommended target dosage is 12 to 24 mg/day administered twice daily. This target dosage range is achieved by daily dosage adjustments, alerting patients to symptoms of orthostatic hypotension, starting at a dose of 1 mg twice daily, then moving to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg twice daily on Days 2, 3, 4, 5, 6, and 7 respectively, to reach the 12 mg/day to 24 mg/day dose range.
Route of Administration: Oral
In Vitro Use Guide
While pacing the hearts at stimulation cycle lengths of 200 or 250 ms, or during natural sinus rhythm (no external pacing), iloperidone 100 nmol/L prolonged MAPD(90) by respectively 9.2 ± 0.9, 11.2 ± 1.6 and 21.4 ± 2.3 ms.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:17:45 UTC 2019
Edited
by admin
on Mon Oct 21 20:17:45 UTC 2019
Record UNII
VPO7KJ050N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ILOPERIDONE
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ILOPERIDONE [VANDF]
Common Name English
HP-873
Code English
ILOPERIDONE [USAN]
Common Name English
4'-(3-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)PIPERIDINO)PROPOXY)-3'-METHOXYACETOPHENONE
Systematic Name English
ILOPERIDONE [ORANGE BOOK]
Common Name English
ILOPERIDONE [WHO-DD]
Common Name English
ILOPERIDONE [MART.]
Common Name English
HP 873
Code English
ETHANONE, 1-(4-(3-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)PROPOXY)-3-METHOXYPHENYL)-
Systematic Name English
ILOPERIDONE [INN]
Common Name English
FANAPT
Brand Name English
ILOPERIDONE [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175430
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
LIVERTOX 498
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
WHO-VATC QN05AX14
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
NCI_THESAURUS C29710
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
WHO-ATC N05AX14
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
Code System Code Type Description
DRUG BANK
DB04946
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
EVMPD
SUB08135MIG
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
WIKIPEDIA
Iloperidone
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
ChEMBL
CHEMBL14376
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
INN
7045
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
MERCK INDEX
M6211
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY Merck Index
NCI_THESAURUS
C83784
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
LactMed
133454-47-4
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
EPA CompTox
133454-47-4
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
PUBCHEM
71360
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
CAS
133454-47-4
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
HSDB
133454-47-4
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
RXCUI
73178
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY RxNorm
MESH
C081732
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
IUPHAR
87
Created by admin on Mon Oct 21 20:17:45 UTC 2019 , Edited by admin on Mon Oct 21 20:17:45 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
MAJOR
Ki
EXCRETED UNCHANGED
Iloperidone counted 0.7 % of dose in excreta from all six human subjects following a single oral dose of 3 mg 14C ILO522.
TARGET -> INHIBITOR
MAJOR
Ki
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
MAJOR
Ki
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
This metabolite counted 4.8 % of dose in excreta from all six human subjects following a single oral dose of 3 mg 14C ILO522.
MINOR
METABOLITE -> PARENT
FECAL; URINE
METABOLITE -> PARENT
This metabolite counted <3.1 % of dose in excreta from all six human subjects following a single oral dose of 3 mg 14C ILO522.
MINOR
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
METABOLITE ACTIVE -> PARENT
The active metabolite P88 accounts for 19.5% and 34.0% of total plasma exposure in EM and PM, respectively.
MAJOR
PLASMA; URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC HIGH-FAT MEAL

FED CONDITION

ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION