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Details

Stereochemistry RACEMIC
Molecular Formula C23H27FN4O3
Molecular Weight 426.4839
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PALIPERIDONE

SMILES

CC1=C(CCN2CCC(CC2)C3=NOC4=C3C=CC(F)=C4)C(=O)N5CCCC(O)C5=N1

InChI

InChIKey=PMXMIIMHBWHSKN-UHFFFAOYSA-N
InChI=1S/C23H27FN4O3/c1-14-17(23(30)28-9-2-3-19(29)22(28)25-14)8-12-27-10-6-15(7-11-27)21-18-5-4-16(24)13-20(18)31-26-21/h4-5,13,15,19,29H,2-3,6-12H2,1H3

HIDE SMILES / InChI
Molecular Formula C23H27FN4O3
Molecular Weight 426.4839
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

Paliperidone (9-OH-risperidone) is the primary active metabolite of the older antipsychotic risperidone. While its specific mechanism of action is unknown, it is believed that paliperidone and risperidone act via similar if not the same pathways. It has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism. Paliperidone is also active as an antagonist at alpha 1 and alpha 2 adrenergic receptors and H1 histaminergic receptors, which may explain some of the other effects of the drug. Paliperidone was approved by the FDA for treatment of schizophrenia on December 20, 2006. Very common adverse effects are: headache, tachycardia, somnolence and insomnia.

CNS Activity

Originator

Approval Year

2006
49
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2438
Schizophrenia
Antagonist
2438
Schizophrenia
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Dopamine D2 receptor
Serotonin 2a (5-HT2a) receptor
Approved
7777
INVEGA
Approved (off-label)
7
PubMed

PubMed

TitleDatePubMed
Effects of CYP2D6 genotypes on plasma concentrations of risperidone and enantiomers of 9-hydroxyrisperidone in Japanese patients with schizophrenia.
2003 Feb
Risperidone plasma levels, clinical response and side-effects.
2005 Aug
Dose-dependent interaction of paroxetine with risperidone in schizophrenic patients.
2005 Dec
Serum concentrations of risperidone and 9-hydroxyrisperidone after administration of the long-acting injectable form of risperidone: evidence from a routine therapeutic drug monitoring service.
2005 Feb
Effect of verapamil on pharmacokinetics and pharmacodynamics of risperidone: in vivo evidence of involvement of P-glycoprotein in risperidone disposition.
2005 Jul
Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6.
2005 Mar
Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia.
2005 Mar
Cytochrome P450 3A inhibitor itraconazole affects plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients.
2005 Nov
P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments.
2005 Oct
Membrane transporter proteins: a challenge for CNS drug development.
2006
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
Intestinal uptake and biodistribution of novel polymeric micelles after oral administration.
2006 Mar 10
Optimization of the separation of some psychotropic drugs and their respective metabolites by liquid chromatography.
2006 May 3
Forty years of antipsychotic Drug research--from haloperidol to paliperidone--with Dr. Paul Janssen.
2007
Paliperidone extended release.
2007
Paliperidone: quo vadis?
2007 Apr
Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study.
2007 Dec 15
Rapidly disintegrating risperidone in subjects with schizophrenia or schizoaffective disorder: a summary of ten phase I clinical trials assessing taste, tablet disintegration time, bioequivalence, and tolerability.
2007 Feb
Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study.
2007 Feb
Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial.
2007 Feb
FDA approves new antipsychotic.
2007 Feb 1
Valproic acid improves psychotic agitation without influencing plasma risperidone levels in schizophrenic patients.
2007 Jan
Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval.
2007 Jan 29
Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study.
2007 Jul
Pharmacokinetics study for hyperprolactinemia among schizophrenics switched from risperidone to risperidone long-acting injection.
2007 Jun
Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS.
2007 Jun 1
Paliperidone (Invega) for schizophrenia.
2007 Mar 12
New drug for schizophrenia.
2007 Mar-Apr
New drugs: paliperidone, dasatinib, and decitabine.
2007 Mar-Apr
A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels.
2007 May
Paliperidone extended-release tablets: a new atypical antipsychotic.
2007 May
A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia.
2007 Sep
Analytical and semipreparative enantioseparation of 9-hydroxyrisperidone, the main metabolite of risperidone, using high-performance liquid chromatography and capillary electrophoresis. Validation and determination of enantiomeric purity.
2007 Sep 7
Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability.
2008
Long-term therapeutic drug monitoring of risperidone and olanzapine identifies altered steady-state pharmacokinetics: a clinical, two-group, naturalistic study.
2008
Gateways to clinical trials. July-August 2008.
2008 Jul-Aug
Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials.
2008 Jun
Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions.
2008 Jun
Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies.
2008 Nov
Apparent seizure and atrial fibrillation associated with paliperidone.
2008 Nov 15
Gateways to clinical trials.
2008 Oct
Antipsychotic drugs inhibit the function of breast cancer resistance protein.
2008 Oct
Paliperidone extended-release for the treatment of schizophrenia.
2008 Oct
ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety.
2008 Oct
Paliperidone as a mood stabilizer: a pre-frontal cortex synaptoneurosomal proteomics comparison with lithium and valproic acid after chronic treatment reveals similarities in protein expression.
2008 Oct 3
Choreatic symptoms during and after treatment with paliperidone and escitalopram.
2008 Sep
Secondary delusional parasitosis treated with paliperidone.
2009 Apr
Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists.
2009 Feb
Paliperidone suppresses the development of the aggressive phenotype in a developmentally sensitive animal model of escalated aggression.
2009 May
Effects of quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone on the survival of human neuronal and immune cells in vitro.
2010 Mar
Patents

Patents

20020146456
2

Sample Use Guides

In Vivo Use Guide
In adults is 6 mg administered once daily In adolescents 12-17 years of age is 3 mg administered once daily
Route of Administration: Oral
In Vitro Use Guide
Paliperidone has dual hyperprolactinemic actions in lactotrophs i) by preserving the coupling of spontaneous electrical activity and prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic dopamine receptor activity in the absence of dopamine, leading to enhanced calcium signaling and secretion.
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:03:58 UTC 2019
Edited
by admin
on Mon Oct 21 21:03:58 UTC 2019
Record UNII
838F01T721
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALIPERIDONE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
PALIPERIDONE [USAN]
Common Name English
4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE, 3-(2-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)ETHYL)-6,7,8,9-TETRAHYDRO-9-HYDROXY-2-METHYL-
Systematic Name English
3-(2-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)ETHYL)-6,7,8,9-TETRAHYDRO-9-HYDROXY-2-METHYL-4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE
Systematic Name English
PALIPERIDONE [MART.]
Common Name English
PALIPERIDONE [EMA EPAR]
Common Name English
9-HYDROXYRISPERIDONE
Common Name English
RISPERIDONE SPECIFIED IMPURITY C [EP]
Common Name English
RO76477
Code English
PALIPERIDONE [WHO-DD]
Common Name English
PALIPERIDONE [INN]
Common Name English
PALIPERIDONE [VANDF]
Common Name English
(9RS)-3-(2-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)PIPERIDIN-1-YL))ETHYL)-9-HYDROXY-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE
Common Name English
PALIPERIDONE [ORANGE BOOK]
Common Name English
PALIPERIDONE [USP-RS]
Common Name English
PALIPERIDONE [MI]
Common Name English
RISPERIDONE IMPURITY, 9-HYDROXYRISPERIDONE- [USP]
Common Name English
R-76477
Code English
RO-76477
Code English
PALIPERIDONE [JAN]
Common Name English
INVEGA
Brand Name English
Classification Tree Code System Code
WHO-ATC N05AX13
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
WHO-VATC QN05AX13
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
LIVERTOX 732
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
NDF-RT N0000175430
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
EMA ASSESSMENT REPORTS INVEGA (AUTHORIZED: PSYCHOTIC DISORDERS)
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
EMA ASSESSMENT REPORTS INVEGA (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
NCI_THESAURUS C66883
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL1621
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
EPA CompTox
144598-75-4
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
WIKIPEDIA
PALIPERIDONE
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
DRUG BANK
DB01267
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
INN
7977
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
CAS
144598-75-4
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
IUPHAR
7258
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
PUBCHEM
115237
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
LactMed
144598-75-4
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
RXCUI
679314
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY RxNorm
NCI_THESAURUS
C66293
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
EVMPD
SUB23268
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
MERCK INDEX
M8357
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY Merck Index
HSDB
144598-75-4
Created by admin on Mon Oct 21 21:03:58 UTC 2019 , Edited by admin on Mon Oct 21 21:03:58 UTC 2019
PRIMARY
Related Record Type Details
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EXCRETED UNCHANGED
AMOUNT EXCRETED
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PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
CYTOCHROME P450 3A4
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Structure of RISPERIDONE
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
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Structure of PALIPERIDONE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
ORAL BIOAVAILABILITY PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
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