Identification

Name
Perphenazine
Accession Number
DB00850  (APRD00429)
Type
Small Molecule
Groups
Approved
Description

An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine.

Structure
Thumb
Synonyms
  • 2-(4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazinyl)ethanol
  • 2-chloro-10-(3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)phenothiazine
  • 4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazineethanol
  • 4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol
  • Chlorpiprazine
  • Etaperazin
  • Etaperazine
  • Ethaperazine
  • Perfenazina
  • Perfenazine
  • Perphenazin
  • Perphénazine
  • Perphenazinum
  • γ-(4-(β-hydroxyethyl)piperazin-1-yl)propyl-2-chlorophenothiazine
External IDs
SC 7105 / Sch 3940
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PerphenazineTablet2 mgOralAa Pharma Inc1976-12-31Not applicableCanada
PerphenazineTablet, sugar coated4 mg/1OralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
PerphenazineTablet16 mgOralAa Pharma Inc1976-12-31Not applicableCanada
PerphenazineTablet, sugar coated16 mg/1OralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
PerphenazineTablet4 mgOralAa Pharma Inc1976-12-31Not applicableCanada
PerphenazineTablet, sugar coated8 mg/1OralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
PerphenazineTablet8 mgOralAa Pharma Inc1976-12-31Not applicableCanada
PerphenazineTablet, sugar coated2 mg/1OralVintage Pharmaceuticals, LLC2007-09-132007-09-13Us
Perphenazine 16 TabTablet16 mgOralPro Doc Limitee1982-12-312010-07-13Canada
Perphenazine 2 Tab 2mgTablet2 mgOralPro Doc Limitee1982-12-312010-07-13Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PerphenazineTablet, film coated8 mg/1OralContract Pharmacy Services Pa2010-04-07Not applicableUs
PerphenazineTablet, film coated4 mg/1OralPar Pharmaceutical1998-12-31Not applicableUs0603 506120180913 8702 15auhoe
PerphenazineTablet, film coated2 mg/1OralSandoz Inc1988-12-08Not applicableUs0781 104620180913 8702 1ef9qia
PerphenazineTablet, film coated8 mg/1OralMajor1998-12-31Not applicableUs
PerphenazineTablet, film coated4 mg/1OralClinical Solutions Wholsesale1998-12-31Not applicableUs58118 506120180913 8702 x7b8v5
PerphenazineTablet, film coated16 mg/1OralState of Florida DOH Central Pharmacy2014-01-01Not applicableUs53808 088520180907 15195 1g34biw
PerphenazineTablet, film coated2 mg/1OralIVAX Pharmaceuticals, Inc.1987-11-012008-11-30Us
PerphenazineTablet, film coated4 mg/1OralRemedy Repack2018-04-19Not applicableUs
PerphenazineTablet, film coated16 mg/1OralClinical Solutions Wholsesale2017-10-30Not applicableUs
PerphenazineTablet, film coated4 mg/1OralRemedy Repack2017-08-23Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Apo Peram Tab 2-25Perphenazine (2 mg) + Amitriptyline Hydrochloride (25 mg)TabletOralApotex Corporation1977-12-312011-08-05Canada
Apo Peram Tab 3-15Perphenazine (3 mg) + Amitriptyline Hydrochloride (15 mg)TabletOralApotex Corporation1977-12-312011-08-05Canada
Elavil Plus TabPerphenazine (2 mg) + Amitriptyline Hydrochloride (25 mg)TabletOralTriton Pharma Inc1973-12-312003-03-08Canada
Etrafon 2 10Perphenazine (2 mg) + Amitriptyline Hydrochloride (10 mg)TabletOralSchering Plough1970-12-312006-08-01Canada
Etrafon A TabPerphenazine (4 mg) + Amitriptyline Hydrochloride (10 mg)TabletOralSchering Plough1963-12-312007-08-03Canada
Etrafon D TabPerphenazine (2 mg) + Amitriptyline Hydrochloride (25 mg)TabletOralSchering Plough1963-12-312007-08-03Canada
Etrafon F TabPerphenazine (4 mg) + Amitriptyline Hydrochloride (25 mg)TabletOralSchering Plough1963-12-312006-08-01Canada
Perphenazine and Amitriptyline HydrochloridePerphenazine (2 mg/1) + Amitriptyline Hydrochloride (10 mg/1)Tablet, film coatedOralMylan Pharmaceuticals1988-11-10Not applicableUs00378 0330 01 nlmimage10 e4087273
Perphenazine and Amitriptyline HydrochloridePerphenazine (2 mg/1) + Amitriptyline Hydrochloride (25 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.1992-08-192010-10-31Us
Perphenazine and Amitriptyline HydrochloridePerphenazine (4 mg/1) + Amitriptyline Hydrochloride (10 mg/1)Tablet, film coatedOralMylan Pharmaceuticals1988-11-10Not applicableUs
International/Other Brands
Decentan (Merck) / Emesinal / Fentazin (Mercury) / Perphenan (Taro) / PZC (Tanabe Mitsubishi Pharma) / Trilafon (Schering-Plough) / Trilifan
Categories
UNII
FTA7XXY4EZ
CAS number
58-39-9
Weight
Average: 403.969
Monoisotopic: 403.148510866
Chemical Formula
C21H26ClN3OS
InChI Key
RGCVKNLCSQQDEP-UHFFFAOYSA-N
InChI
InChI=1S/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2
IUPAC Name
2-{4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazin-1-yl}ethan-1-ol
SMILES
OCCN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1

Pharmacology

Indication

For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults.

Associated Conditions
Pharmacodynamics

Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol.

Mechanism of action

Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(1A) dopamine receptor
antagonist
Human
UCalmodulin
inhibitor
Human
Absorption

Absolute bioavailability is 40% following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination

Perphenazine is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation.

Half life

8-12 hours, but ranges up to 20 hours.

Clearance
Not Available
Toxicity

Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours. Oral LD50=318 mg/kg (rat); IPR LD50=64 mg/kg (mouse)

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 alleleADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, more side effects.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, more side effects.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Perphenazine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Perphenazine can be decreased when combined with (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Perphenazine.
2,5-Dimethoxy-4-ethylamphetaminePerphenazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetaminePerphenazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Perphenazine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Perphenazine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Perphenazine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Perphenazine.
4-Bromo-2,5-dimethoxyamphetaminePerphenazine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
Food Interactions
  • Avoid alcohol.
  • Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
  • Take with food.

References

Synthesis Reference
US2860138
General References
Not Available
External Links
Human Metabolome Database
HMDB0014988
KEGG Drug
D00503
KEGG Compound
C07427
PubChem Compound
4748
PubChem Substance
46507058
ChemSpider
4586
BindingDB
50130273
ChEBI
8028
ChEMBL
CHEMBL567
Therapeutic Targets Database
DAP000100
PharmGKB
PA450882
IUPHAR
209
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Perphenazine
ATC Codes
N05AB03 — Perphenazine
AHFS Codes
  • 28:16.08.24 — Phenothiazines
FDA label
Download (360 KB)
MSDS
Download (74.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2Unknown StatusTreatmentDependence, Cocaine / Schizophrenic Disorders1
3Active Not RecruitingTreatmentPsychotic Disorder NOS / Schizophrenic Disorders1
3CompletedTreatmentAlzheimer's Disease (AD) / Dementia, Vascular / Dementias1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedPreventionSchizophrenic Disorders1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4CompletedTreatmentSchizophrenic Disorders2
4WithdrawnPreventionSchizophrenic Disorders1
Not AvailableActive Not RecruitingTreatmentSchizophrenia Relapse1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedTreatmentSchizophrenic Disorders2
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1

Pharmacoeconomics

Manufacturers
  • Pharmaceutical assoc inc
  • Schering corp sub schering plough corp
  • Ivax pharmaceuticals inc
  • Sandoz inc
  • Vintage pharmaceuticals inc
Packagers
  • Amerisource Health Services Corp.
  • Comprehensive Consultant Services Inc.
  • Coupler Enterprises Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Goldline Laboratories Inc.
  • Heartland Repack Services LLC
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • PD-Rx Pharmaceuticals Inc.
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Richmond Pharmacy
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Tya Pharmaceuticals
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • Warrick Pharmaceuticals Corp.
Dosage forms
FormRouteStrength
TabletOral
TabletOral16 mg
TabletOral2 mg
TabletOral4 mg/1
TabletOral4 mg
TabletOral8 mg
TabletOral8 mg/1
Tablet, film coatedOral16 mg/1
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral4 mg/1
Tablet, film coatedOral8 mg/1
Tablet, sugar coatedOral16 mg/1
Tablet, sugar coatedOral2 mg/1
Tablet, sugar coatedOral4 mg/1
Tablet, sugar coatedOral8 mg/1
Tablet, film coatedOral
LiquidOral3.2 mg
LiquidOral16 mg
SolutionIntramuscular; Intravenous5 mg
SyrupOral2 mg
Prices
Unit descriptionCostUnit
Perphenazine 16 mg tablet1.73USD tablet
Perphenazine 8 mg tablet1.28USD tablet
Perphenazine 4 mg tablet1.05USD tablet
Perphenazine 2 mg tablet0.77USD tablet
Apo-Perphenazine 16 mg Tablet0.13USD tablet
Apo-Perphenazine 8 mg Tablet0.09USD tablet
Apo-Perphenazine 4 mg Tablet0.08USD tablet
Apo-Perphenazine 2 mg Tablet0.07USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)97 °CPhysProp
boiling point (°C)278-281 °C at 1.00E+00 mm HgPhysProp
water solubility28.3 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.20HANSCH,C ET AL. (1995)
logS-4.16ADME Research, USCD
pKa7.94SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0237 mg/mLALOGPS
logP4.15ALOGPS
logP3.69ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)15.59ChemAxon
pKa (Strongest Basic)8.21ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.95 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity116.1 m3·mol-1ChemAxon
Polarizability44.77 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9476
Blood Brain Barrier+0.9683
Caco-2 permeable-0.5126
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.7689
Renal organic cation transporterInhibitor0.5807
CYP450 2C9 substrateNon-substrate0.7442
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.6813
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.9278
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9089
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7548
Ames testNon AMES toxic0.8093
CarcinogenicityNon-carcinogens0.8836
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0725 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7745
hERG inhibition (predictor II)Inhibitor0.7066
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.95 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9450000000-c13808005c7ad3a43067
Mass Spectrum (Electron Ionization)MSsplash10-0002-4591100000-97d36958b3e0fe519db6
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/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0zfr-0410900000-0910eefd789edd7f94c9
MS/MS Spectrum - , positiveLC-MS/MSsplash10-006x-3940100000-e722b009e1511bd2bb57
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0f6t-2930000000-57d820b40a3c2c072840

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / N-alkylpiperazines / Benzenoids / Aryl chlorides / 1,4-thiazines / Trialkylamines / 1,2-aminoalcohols / Azacyclic compounds / Primary alcohols
show 3 more
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / N-alkylpiperazine / Para-thiazine / Aryl chloride / Aryl halide / 1,4-diazinane
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, N-(2-hydroxyethyl)piperazine, organochlorine compound, N-alkylpiperazine (CHEBI:8028)

Targets

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. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
  2. Hoyberg OJ, Fensbo C, Remvig J, Lingjaerde O, Sloth-Nielsen M, Salvesen I: Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. Acta Psychiatr Scand. 1993 Dec;88(6):395-402. [PubMed:7508675]
  3. Qin ZH, Weiss B: Dopamine receptor blockade increases dopamine D2 receptor and glutamic acid decarboxylase mRNAs in mouse substantia nigra. Eur J Pharmacol. 1994 Sep 15;269(1):25-33. [PubMed:7828655]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Talvik M, Nordstrom AL, Larsen NE, Jucaite A, Cervenka S, Halldin C, Farde L: A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration. Psychopharmacology (Berl). 2004 Sep;175(2):148-53. Epub 2004 Mar 6. [PubMed:15007534]
  6. Farde L, Wiesel FA, Nordstrom AL, Sedvall G: D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology (Berl). 1989;99 Suppl:S28-31. [PubMed:2573104]
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 activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Dolzan V, Plesnicar BK, Serretti A, Mandelli L, Zalar B, Koprivsek J, Breskvar K: Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment. Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):809-15. [PubMed:17455212]
  2. Farde L, Wiesel FA, Nordstrom AL, Sedvall G: D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology (Berl). 1989;99 Suppl:S28-31. [PubMed:2573104]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Titin binding
Specific Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name
CALM1
Uniprot ID
P0DP23
Uniprot Name
Calmodulin
Molecular Weight
16837.47 Da
References
  1. Mongin AA, Cai Z, Kimelberg HK: Volume-dependent taurine release from cultured astrocytes requires permissive [Ca(2+)](i) and calmodulin. Am J Physiol. 1999 Oct;277(4 Pt 1):C823-32. [PubMed:10516112]
  2. Kawai M, Nakashima A, Ueno M, Ushimaru T, Aiba K, Doi H, Uritani M: Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature. Curr Genet. 2001 May;39(3):166-74. [PubMed:11409178]
  3. Edlind T, Smith L, Henry K, Katiyar S, Nickels J: Antifungal activity in Saccharomyces cerevisiae is modulated by calcium signalling. Mol Microbiol. 2002 Oct;46(1):257-68. [PubMed:12366848]
  4. Natochin YuV, Shakhmatova EI, Bakos P: Water and sodium transport: effects of calcium channel blocker and calmodulin antagonists on the apical and basolateral membranes of amphibian epithelia. Gen Physiol Biophys. 1987 Feb;6(1):35-44. [PubMed:2885243]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Otani K, Aoshima T: Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit. 2000 Feb;22(1):118-21. [PubMed:10688273]
  2. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression]. Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. [PubMed:16910628]
  3. Linnet K, Wiborg O: Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Clin Pharmacol Ther. 1996 Jul;60(1):41-7. [PubMed:8689810]
  4. Ozdemir V, Naranjo CA, Herrmann N, Reed K, Sellers EM, Kalow W: Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo. Clin Pharmacol Ther. 1997 Sep;62(3):334-47. [PubMed:9333110]
  5. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. [PubMed:9616188]
  6. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data supporting this enzyme action are limited to in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Olesen OV, Linnet K: Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol. 2000 Dec;50(6):563-71. [PubMed:11136295]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:31