Identification

Name
Paliperidone
Accession Number
DB01267
Type
Small Molecule
Groups
Approved
Description

Paliperidone 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.

Structure
Thumb
Synonyms
  • 9-hydroxyrisperidone
  • Paliperidona
External IDs
R-76477 / RO-76477 / RO76477
Product Ingredients
IngredientUNIICASInChI Key
Paliperidone palmitateR8P8USM8FR199739-10-1VOMKSBFLAZZBOW-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InvegaTablet, extended release3 mgOralJanssen Pharmaceuticals2007-10-02Not applicableCanada
InvegaTablet, extended release9 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release12 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release3 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release6 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release6 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release3 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release9 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release6 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
InvegaTablet, extended release1.5 mgOralJanssen Cilag International Nv2007-06-25Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-paliperidoneTablet, extended release6 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-paliperidoneTablet, extended release3 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
PaliperidoneTablet, film coated, extended release6 mg/1OralMylan Institutional Inc.2016-09-15Not applicableUs
PaliperidoneTablet, extended release3 mg/1OralSun Pharmaceutical Industries, Inc.2018-08-01Not applicableUs
PaliperidoneTablet, extended release9 mg/1OralNorthstar RxLLC2018-10-15Not applicableUs
PaliperidoneTablet, film coated, extended release3 mg/1OralMylan Pharmaceuticals Inc.2015-09-24Not applicableUs
PaliperidoneTablet, extended release9 mg/1OralSun Pharmaceutical Industries, Inc.2018-08-01Not applicableUs
PaliperidoneTablet, film coated, extended release3 mg/1OralActavis Pharma, Inc.2015-09-24Not applicableUs
PaliperidoneTablet, film coated, extended release6 mg/1OralCarilion Materials Management2015-09-24Not applicableUs
PaliperidoneTablet, film coated, extended release6 mg/1OralAmerican Health Packaging2018-08-302018-09-01Us
International/Other Brands
Invega
Categories
UNII
838F01T721
CAS number
144598-75-4
Weight
Average: 426.4839
Monoisotopic: 426.206718955
Chemical Formula
C23H27FN4O3
InChI Key
PMXMIIMHBWHSKN-UHFFFAOYSA-N
InChI
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
IUPAC Name
3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-4H,6H,7H,8H,9H-pyrido[1,2-a]pyrimidin-4-one
SMILES
CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCC(O)C2=N1

Pharmacology

Indication

For the treatment of schizophrenia.

Associated Conditions
Pharmacodynamics

Paliperidone is an atypical antipsychotic developed by Janssen Pharmaceutica. Chemically, paliperidone is primary active metabolite of the older antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone). While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not the same, pathways.

Mechanism of action

Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown, but 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.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Human
AD(2) dopamine receptor
antagonist
Human
UHistamine H1 receptor
agonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
AD(4) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 1D
antagonist
Human
AD(3) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2C
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
agonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 7Not AvailableHuman
Absorption

The absolute oral bioavailability of paliperidone following paliperidone administration is 28%.

Volume of distribution
  • 487 L
Protein binding

The plasma protein binding of racemic paliperidone is 74%.

Metabolism

Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, in vivo results indicate that these isozymes play a limited role in the overall elimination of paliperidone. Four primary metabolic pathways have been identified in vivo, none of which could be shown to account for more than 10% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Paliperidone does not undergo extensive metabolism and a significant portion of its metabolism occurs in the kidneys.

Route of elimination

One week following administration of a single oral dose of 1 mg immediate-release 14C-paliperidone to 5 healthy volunteers, 59% (range 51% – 67%) of the dose was excreted unchanged into urine, 32% (26% – 41%) of the dose was recovered as metabolites, and 6% – 12% of the dose was not recovered.

Half life

The terminal elimination half-life of paliperidone is approximately 23 hours.

Clearance
Not Available
Toxicity

The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Paliperidone is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Paliperidone is combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Paliperidone.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Paliperidone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Paliperidone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Paliperidone is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Paliperidone.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Paliperidone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Paliperidone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Paliperidone.
Food Interactions
  • Avoid alcohol.

References

Synthesis Reference

Santiago Ini, Naama Chasid, Kobi Chen, Osnat Porter-Kleks, "Pure paliperidone and processes for preparing thereof." U.S. Patent US20080171876, issued July 17, 2008.

US20080171876
General References
  1. Jones MP, Nicholl D, Trakas K: Efficacy and tolerability of paliperidone ER and other oral atypical antipsychotics in schizophrenia. Int J Clin Pharmacol Ther. 2010 Jun;48(6):383-99. [PubMed:20497747]
  2. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. [PubMed:18537577]
External Links
Human Metabolome Database
HMDB0015396
KEGG Drug
D05339
PubChem Compound
115237
PubChem Substance
46506296
ChemSpider
103109
BindingDB
50252513
ChEBI
83804
ChEMBL
CHEMBL1621
Therapeutic Targets Database
DAP000847
PharmGKB
PA163518919
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Paliperidone
ATC Codes
N05AX13 — Paliperidone
AHFS Codes
  • 28:16.08.04 — Atypical Antipsychotics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableEpilepsies / Schizophrenic Disorders1
1CompletedBasic ScienceBipolar Disorder (BD) / Depressive Disorders / Psychotic Disorder NOS / Schizophrenic Disorders1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherAntipsychotics / Immunoassay1
1CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders2
1CompletedTreatmentSchizophrenic Disorders8
1, 2Active Not RecruitingOtherSchizophrenic Disorders1
2CompletedTreatmentChronic Schizophrenia / Schizoaffective Disorders1
2CompletedTreatmentObsessive Compulsive Disorder (OCD)1
2CompletedTreatmentSchizophrenic Disorders2
2CompletedTreatmentSchizophrenic Disorders / Sleeplessness1
2RecruitingTreatmentSchizophrenic Disorders1
2TerminatedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
2, 3Not Yet RecruitingTreatmentPharmacotherapy / Schizophrenia and Related Disorders / Stimulant Abuse / Stimulant Dependence / Stimulant Use With Stimulant-Induced Psychotic Disorder (Diagnosis)1
3Active Not RecruitingTreatmentAmphetamine Dependence / Heroin Dependence1
3Active Not RecruitingTreatmentPsychotic Disorder NOS / Schizophrenic Disorders1
3Active Not RecruitingTreatmentSchizophrenic Disorders2
3CompletedPreventionSchizoaffective Disorders1
3CompletedPreventionSchizophrenic Disorders1
3CompletedTreatmentAffective Psychosis, Bipolar / Bipolar Disorder (BD) / Mania1
3CompletedTreatmentAutism, Early Infantile1
3CompletedTreatmentBipolar Disorder (BD)1
3CompletedTreatmentBipolar Disorder (BD) / Moods Disorders1
3CompletedTreatmentPsychotic Disorder NOS / Schizoaffective Disorders2
3CompletedTreatmentPsychotic Disorder NOS / Schizophrenic Disorders1
3CompletedTreatmentSchizophrenic Disorders29
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedNot AvailableSchizophrenic Disorders3
4CompletedPreventionSchizophrenic Disorders1
4CompletedTreatmentAcute Disease / Psychomotor Agitation1
4CompletedTreatmentFirst Episode Psychosis1
4CompletedTreatmentMajor Depressive Disorder (MDD) / Suicidal Thoughts1
4CompletedTreatmentMethamphetamine Dependence1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders3
4CompletedTreatmentSchizophrenic Disorders20
4Not Yet RecruitingTreatmentSchizophrenic Disorders2
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4RecruitingTreatmentSchizophrenia (Recent-onset)1
4RecruitingTreatmentSchizophrenic Disorders2
4TerminatedNot AvailableSchizophrenic Disorders1
4TerminatedPreventionSchizophrenic Disorders1
4TerminatedTreatmentPediatric Bipolar Disorder1
4TerminatedTreatmentSchizophrenic Disorders2
4Unknown StatusTreatmentSchizophrenic Disorders1
4WithdrawnPreventionSchizophrenic Disorders1
4WithdrawnTreatmentBipolar Disorder (BD)1
4WithdrawnTreatmentPosttraumatic Stress Disorders1
Not AvailableActive Not RecruitingTreatmentSchizophrenia Relapse1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedTreatmentMethamphetamine Dependence1
Not AvailableCompletedTreatmentSchizophrenic Disorders1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableEnrolling by InvitationNot AvailableSchizophrenia Spectrum and Other Psychotic Disorders1
Not AvailableRecruitingNot AvailableSchizophrenic Disorders1
Not AvailableUnknown StatusTreatmentSchizophrenic Disorders / Schizophreniform1
Not AvailableWithdrawnTreatmentSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alza Corp.
  • Interquim SA
  • Janssen-Ortho Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Physician Partners Ltd.
  • Quality Care
  • Rebel Distributors Corp.
Dosage forms
FormRouteStrength
Tablet, extended releaseOral1.5 mg
Tablet, extended releaseOral12 mg
Tablet, extended releaseOral3 mg
Tablet, extended releaseOral3 mg/1
Tablet, extended releaseOral6 mg
Tablet, extended releaseOral6 mg/1
Tablet, extended releaseOral9 mg
InjectionIntramuscular117 mg/0.75mL
InjectionIntramuscular156 mg/1mL
InjectionIntramuscular234 mg/1.5mL
InjectionIntramuscular39 mg/0.25mL
InjectionIntramuscular78 mg/0.5mL
Suspension, extended releaseIntramuscular100 mg
Suspension, extended releaseIntramuscular150 mg
Suspension, extended releaseIntramuscular25 mg
Suspension, extended releaseIntramuscular50 mg
Suspension, extended releaseIntramuscular75 mg
Injection, suspension, extended releaseIntramuscular273 mg/0.875mL
Injection, suspension, extended releaseIntramuscular410 mg/1.315mL
Injection, suspension, extended releaseIntramuscular546 mg/1.75mL
Injection, suspension, extended releaseIntramuscular819 mg/2.625mL
Suspension, extended releaseIntramuscular175 mg
Suspension, extended releaseIntramuscular263 mg
Suspension, extended releaseIntramuscular350 mg
Suspension, extended releaseIntramuscular525 mg
Tablet, extended releaseOral1.5 mg/1
Tablet, extended releaseOral9 mg/1
Tablet, film coated, extended releaseOral1.5 mg/1
Tablet, film coated, extended releaseOral3 mg/1
Tablet, film coated, extended releaseOral6 mg/1
Tablet, film coated, extended releaseOral9 mg/1
Injection, suspension, extended releaseIntramuscular100 mg
Injection, suspension, extended releaseIntramuscular150 mg
Injection, suspension, extended releaseIntramuscular25 mg
Injection, suspension, extended releaseIntramuscular50 mg
Injection, suspension, extended releaseIntramuscular75 mg
Prices
Unit descriptionCostUnit
Invega sustenna 39 mg pref syringe296.45USD syringe
Invega er 6 mg tablet28.62USD tablet
Invega er 9 mg tablet23.59USD tablet
Invega er 3 mg tablet23.09USD tablet
Invega er 1.5 mg tablet15.72USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5254556No1993-10-192010-10-27Us
CA2494234No2009-10-272023-07-28Canada
CA2000786No1999-01-262009-10-16Canada
US6077843Yes2000-06-202017-11-12Us
US6555544Yes2003-04-292019-05-10Us
US9439906No2016-09-132031-01-26Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insoluble in waterNot Available
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.297 mg/mLALOGPS
logP2.3ALOGPS
logP1.76ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)13.74ChemAxon
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.17 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity116.04 m3·mol-1ChemAxon
Polarizability45.95 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7928
Caco-2 permeable-0.5496
P-glycoprotein substrateSubstrate0.7449
P-glycoprotein inhibitor IInhibitor0.7011
P-glycoprotein inhibitor IIInhibitor0.8229
Renal organic cation transporterNon-inhibitor0.6231
CYP450 2C9 substrateNon-substrate0.7721
CYP450 2D6 substrateSubstrate0.5131
CYP450 3A4 substrateSubstrate0.7154
CYP450 1A2 substrateNon-inhibitor0.7379
CYP450 2C9 inhibitorNon-inhibitor0.7395
CYP450 2D6 inhibitorNon-inhibitor0.5326
CYP450 2C19 inhibitorNon-inhibitor0.7815
CYP450 3A4 inhibitorNon-inhibitor0.6468
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7558
Ames testNon AMES toxic0.518
CarcinogenicityNon-carcinogens0.7995
BiodegradationNot ready biodegradable0.9908
Rat acute toxicity3.7859 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8366
hERG inhibition (predictor II)Inhibitor0.7061
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0000900000-455daaf1442d16f7bdaa
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0010900000-dfa5205279a00e3db1e5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090300000-40916890e9a9a7068fa9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090000000-e69a1027f43e06f96a84
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090000000-5a71379b6aa632f43ea0

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyridopyrimidines. These are compounds containing a pyridopyrimidine, which consists of a pyridine fused to a pyrimidine. Pyridine is 6-membered ring consisting of five carbon atoms and a nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridopyrimidines
Sub Class
Not Available
Direct Parent
Pyridopyrimidines
Alternative Parents
Benzisoxazoles / Aralkylamines / Pyrimidones / Aryl fluorides / Benzenoids / Piperidines / Pyridines and derivatives / Isoxazoles / Heteroaromatic compounds / Lactams
show 8 more
Substituents
Pyridopyrimidine / Benzisoxazole / Pyrimidone / Aralkylamine / Aryl fluoride / Aryl halide / Benzenoid / Piperidine / Pyridine / Pyrimidine
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, secondary alcohol, pyridopyrimidine, 1,2-benzoxazoles, heteroarylpiperidine (CHEBI:83804)

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. Cohen LJ: Risperidone. Pharmacotherapy. 1994 May-Jun;14(3):253-65. [PubMed:7524043]
  2. He H, Richardson JS: A pharmacological, pharmacokinetic and clinical overview of risperidone, a new antipsychotic that blocks serotonin 5-HT2 and dopamine D2 receptors. Int Clin Psychopharmacol. 1995 Mar;10(1):19-30. [PubMed:7542676]
  3. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  4. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
  5. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
  6. Yamada Y, Ohno Y, Nakashima Y, Fukuda M, Takayanagi R, Sato H, Tsuchiya F, Sawada Y, Iga T: Prediction and assessment of extrapyramidal side effects induced by risperidone based on dopamine D(2) receptor occupancy. Synapse. 2002 Oct;46(1):32-7. [PubMed:12211096]
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. Cohen LJ: Risperidone. Pharmacotherapy. 1994 May-Jun;14(3):253-65. [PubMed:7524043]
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
  3. Regenthal R, Kunstler U, Hesse S, Sabri O, Preiss R: D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients. Int J Clin Pharmacol Ther. 2005 Aug;43(8):370-8. [PubMed:16119512]
  4. Remington G, Mamo D, Labelle A, Reiss J, Shammi C, Mannaert E, Mann S, Kapur S: A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry. 2006 Mar;163(3):396-401. [PubMed:16513859]
  5. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
  6. Yamada Y, Ohno Y, Nakashima Y, Fukuda M, Takayanagi R, Sato H, Tsuchiya F, Sawada Y, Iga T: Prediction and assessment of extrapyramidal side effects induced by risperidone based on dopamine D(2) receptor occupancy. Synapse. 2002 Oct;46(1):32-7. [PubMed:12211096]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Details
3. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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. Cohen LJ: Risperidone. Pharmacotherapy. 1994 May-Jun;14(3):253-65. [PubMed:7524043]
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
  3. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
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. Cohen LJ: Risperidone. Pharmacotherapy. 1994 May-Jun;14(3):253-65. [PubMed:7524043]
  2. Eltze M: In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1996 Jan 4;295(1):69-73. [PubMed:8925876]
  3. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. [PubMed:15907153]
  4. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. [PubMed:15992090]
  5. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
  6. Nourian Z, Mow T, Muftic D, Burek S, Pedersen ML, Matz J, Mulvany MJ: Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of alpha1-adrenoceptor function. Psychopharmacology (Berl). 2008 Jul;199(1):15-27. doi: 10.1007/s00213-007-1064-9. Epub 2008 Jun 10. [PubMed:18542932]
  7. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
  8. Sleight AJ, Koek W, Bigg DC: Binding of antipsychotic drugs at alpha 1A- and alpha 1B-adrenoceptors: risperidone is selective for the alpha 1B-adrenoceptors. Eur J Pharmacol. 1993 Jul 20;238(2-3):407-10. [PubMed:7691623]
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
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Cohen LJ: Risperidone. Pharmacotherapy. 1994 May-Jun;14(3):253-65. [PubMed:7524043]
  2. Eltze M: In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1996 Jan 4;295(1):69-73. [PubMed:8925876]
  3. Fenton C, Scott LJ: Risperidone: a review of its use in the treatment of bipolar mania. CNS Drugs. 2005;19(5):429-44. [PubMed:15907153]
  4. Keks NA, Culhane C: Risperidone (Risperdal): clinical experience with a new antipsychosis drug. Expert Opin Investig Drugs. 1999 Apr;8(4):443-52. [PubMed:15992090]
  5. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
  6. Nourian Z, Mow T, Muftic D, Burek S, Pedersen ML, Matz J, Mulvany MJ: Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of alpha1-adrenoceptor function. Psychopharmacology (Berl). 2008 Jul;199(1):15-27. doi: 10.1007/s00213-007-1064-9. Epub 2008 Jun 10. [PubMed:18542932]
  7. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
  8. Sleight AJ, Koek W, Bigg DC: Binding of antipsychotic drugs at alpha 1A- and alpha 1B-adrenoceptors: risperidone is selective for the alpha 1B-adrenoceptors. Eur J Pharmacol. 1993 Jul 20;238(2-3):407-10. [PubMed:7691623]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
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 ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
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. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
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. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [PubMed:7520908]
  2. Megens AA, Awouters FH, Schotte A, Meert TF, Dugovic C, Niemegeers CJ, Leysen JE: Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology (Berl). 1994 Feb;114(1):9-23. [PubMed:7531353]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Acts as an inactivating antagonist competing for the ligand binding site and producing lasting inactivation of the receptor.
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. Knight JA, Smith C, Toohey N, Klein MT, Teitler M: Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists. Mol Pharmacol. 2009 Feb;75(2):374-80. doi: 10.1124/mol.108.052084. Epub 2008 Nov 7. [PubMed:18996971]
  2. Toohey N, Klein MT, Knight J, Smith C, Teitler M: Human 5-HT7 receptor-induced inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and other "inactivating antagonists". Mol Pharmacol. 2009 Sep;76(3):552-9. doi: 10.1124/mol.109.056283. Epub 2009 Jun 9. [PubMed:19509219]
  3. Teitler M, Toohey N, Knight JA, Klein MT, Smith C: Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions. Psychopharmacology (Berl). 2010 Dec;212(4):687-97. doi: 10.1007/s00213-010-2001-x. Epub 2010 Sep 9. [PubMed:20827463]

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. Gunes A, Spina E, Dahl ML, Scordo MG: ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety. Ther Drug Monit. 2008 Oct;30(5):628-33. doi: 10.1097/FTD.0b013e3181858ca9. [PubMed:18708991]
  2. Invega (Paliperidone) FDA label [Link]
  3. Invega Trinza (Paliperidone palmitate) FDA Label [Link]
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. Boerth JM, Caley CF, Goethe JW: Interpreting serum risperidone concentrations. Pharmacotherapy. 2005 Feb;25(2):299-302. [PubMed:15767244]
  2. Invega Trinza (Paliperidone palmitate) FDA Label [Link]
  3. Invega (Paliperidone) FDA label [Link]
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. Yasui-Furukori N, Hidestrand M, Spina E, Facciola G, Scordo MG, Tybring G: Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes. Drug Metab Dispos. 2001 Oct;29(10):1263-8. [PubMed:11560868]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Invega Trinza (Paliperidone palmitate) FDA Label [Link]
  2. Invega (Paliperidone) FDA label [Link]

Drug created on May 16, 2007 14:09 / Updated on December 10, 2018 06:10