Identification

Name
Thioridazine
Accession Number
DB00679  (APRD00596)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

A phenothiazine antipsychotic used in the management of psychoses, including schizophrenia, and in the control of severely disturbed or agitated behavior. It has little antiemetic activity. Thioridazine has a higher incidence of antimuscarinic effects, but a lower incidence of extrapyramidal symptoms, than chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p618).

Thioridazine was withdrawn worldwide in 2005 due to it's association with cardiac arrythmias.

Structure
Thumb
Synonyms
  • 10-[2-(1-methyl-2-piperidyl)ethyl]-2-methylsulfanyl-phenothiazine
  • 2-Methylmercapto-10-(2-(N-methyl-2-piperidyl)ethyl)phenothiazine
  • 3-Methylmercapto-N-(2'-(N-methyl-2-piperidyl)ethyl)phenothiazine
  • Thioridazin
  • Thioridazinum
  • Tioridazina
External IDs
TP-21
Product Ingredients
IngredientUNIICASInChI Key
Thioridazine Hydrochloride4WCI67NK8M130-61-0NZFNXWQNBYZDAQ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MellarilLiquid30 mgOralNovartis1997-08-152001-07-30Canada
MellarilSuspension10 mgOralNovartis1964-12-312001-07-30Canada
Mellaril Tab 100mgTablet100 mgOralSandoz1959-12-311996-09-05Canada
Mellaril Tab 10mgTablet10 mgOralSandoz1959-12-311997-08-12Canada
Mellaril Tab 200mgTablet200 mgOralSandoz1959-12-311996-09-05Canada
Mellaril Tab 25mgTablet25 mgOralSandoz1959-12-311996-09-05Canada
Mellaril Tab 50mgTablet50 mgOralSandoz1959-12-311996-09-23Canada
PMS Thioridazine Tab 50mgTablet50 mgOralPharmascience Inc1984-12-312004-05-24Canada
Thioridazine Oral Sus 2mg/mlSuspension2 mgOralSands Pharm1972-12-311996-09-10Canada
Thioridazine Tab 10mgTablet10 mgOralDuchesnay Inc.1978-12-312003-07-18Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Novo-ridazine (thioridazine Oral Suspension) - 2 mg/mlSuspension2 mgOralNovopharm Limited1996-09-182005-08-10Canada
Novo-ridazine 100mgTablet100 mgOralNovopharm Limited1972-12-312005-08-10Canada
Novo-ridazine 10mgTablet10 mgOralNovopharm Limited1972-12-312005-08-10Canada
Novo-ridazine 25mgTablet25 mgOralNovopharm Limited1972-12-312005-08-10Canada
Novo-ridazine 50mgTablet50 mgOralNovopharm Limited1972-12-312005-08-10Canada
Novo-ridazine Tab 200mgTablet200 mgOralNovopharm Limited1973-12-312005-08-10Canada
PMS-thioridazine 100mg/tab USPTablet100 mgOralPharmascience Inc1984-12-312004-05-24Canada
PMS-thioridazine 10mg/tab USPTablet10 mgOralPharmascience Inc1984-12-312004-05-24Canada
PMS-thioridazine Solution 30mg/mlSolution30 mgOralPharmascience Inc1988-12-312004-05-24Canada
PMS-thioridazine Solution 5mg/mlSolution5 mgOralPharmascience Inc1988-12-311996-09-09Canada
International/Other Brands
Aldazine / Mallorol / Malloryl / Meleril / Mellaril-S / Mellerets / Mellerette / Melleretten / Melleril / Novoridazine / Orsanil / Ridazin / Ridazine / Sonapax / Thioril
Categories
UNII
N3D6TG58NI
CAS number
50-52-2
Weight
Average: 370.575
Monoisotopic: 370.153740222
Chemical Formula
C21H26N2S2
InChI Key
KLBQZWRITKRQQV-UHFFFAOYSA-N
InChI
InChI=1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3
IUPAC Name
10-[2-(1-methylpiperidin-2-yl)ethyl]-2-(methylsulfanyl)-10H-phenothiazine
SMILES
CSC1=CC2=C(SC3=CC=CC=C3N2CCC2CCCCN2C)C=C1

Pharmacology

Indication

For the treatment of schizophrenia and generalized anxiety disorder.

Associated Conditions
Pharmacodynamics

Thioridazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Thioridazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

Mechanism of action

Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(1A) dopamine receptor
antagonist
Human
AAlpha-1A adrenergic receptor
antagonist
Human
AAlpha-1B adrenergic receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
Absorption

60%

Volume of distribution
Not Available
Protein binding

95%

Metabolism

Hepatic

Route of elimination
Not Available
Half life

21-25 hours

Clearance
Not Available
Toxicity

LD50=956-1034 mg/kg (Orally in rats); Agitation, blurred vision, coma, confusion, constipation, difficulty breathing, dilated or constricted pupils, diminished flow of urine, dry mouth, dry skin, excessively high or low body temperature, extremely low blood pressure, fluid in the lungs, heart abnormalities, inability to urinate, intestinal blockage, nasal congestion, restlessness, sedation, seizures, shock

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 InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*9Not Available2615-2617delAAGADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*10Not Available100C>T / 1661G>C  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*14BNot Available1758G>AADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*17Not Available1023C>T / 2850C>TADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*18Not Available4133dupGTGCCCACTADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*29Not Available1659G>A / 1661G>C  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*41Not Available2988G>AADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*49Not Available100C>T / -1426C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*50Not Available1720A>CADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*54Not Available100C>T / 1039C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*55Not Available1661G>C / 2850C>T  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*59Not Available1661G>C / 2291G>A  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details
Cytochrome P450 2D6CYP2D6*72Not Available-1426C>T / -1235A>G  … show all ADR InferredReduced CYP2D6 activity associated with Torsades de pointes and/or sudden death.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Thioridazine.
(R)-warfarinThe risk or severity of adverse effects can be increased when Thioridazine is combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Thioridazine.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Thioridazine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Thioridazine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Thioridazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Thioridazine is combined with 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Thioridazine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Thioridazine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Thioridazine is combined with 4-hydroxycoumarin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014817
KEGG Drug
D00373
PubChem Compound
5452
PubChem Substance
46509070
ChemSpider
5253
BindingDB
50002338
ChEBI
9566
ChEMBL
CHEMBL479
Therapeutic Targets Database
DAP000476
PharmGKB
PA451666
IUPHAR
100
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Thioridazine
ATC Codes
N05AC02 — Thioridazine
MSDS
Download (44.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedNot AvailableHealthy Volunteers1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Actavis mid atlantic llc
  • Alpharma us pharmaceuticals division
  • Hi tech pharmacal co inc
  • Pharmaceutical assoc inc div beach products
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
  • Roxane laboratories inc
  • Ivax pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Heartland Repack Services LLC
  • Interpharm Pharmaceutical Products Inc.
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Novartis AG
  • Pharmaceutical Packaging Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Professional Co.
  • Qualitest
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
Dosage forms
FormRouteStrength
LiquidOral30 mg
SuspensionOral10 mg
TabletOral100 mg
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
TabletOral200 mg
SolutionOral30 mg
SolutionOral5 mg
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
SuspensionOral2 mg
Prices
Unit descriptionCostUnit
Thioridazine hcl powder11.16USD g
Thioridazine HCl 200 mg tablet1.14USD tablet
Thioridazine HCl 150 mg tablet1.01USD tablet
Thioridazine HCl 100 mg tablet0.69USD tablet
Thioridazine 100 mg tablet0.67USD tablet
Thioridazine HCl 50 mg tablet0.61USD tablet
Thioridazine 50 mg tablet0.58USD tablet
Thioridazine HCl 25 mg tablet0.49USD tablet
Thioridazine 25 mg tablet0.47USD tablet
Thioridazine HCl 15 mg tablet0.45USD tablet
Thioridazine HCl 10 mg tablet0.35USD tablet
Thioridazine 10 mg tablet0.33USD 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)73 °CPhysProp
boiling point (°C)230 °C at 2.00E-02 mm HgPhysProp
water solubility0.0336 mg/LNot Available
logP5.90HANSCH,C ET AL. (1995)
pKa9.5EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.000855 mg/mLALOGPS
logP5.93ALOGPS
logP5.47ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity113.52 m3·mol-1ChemAxon
Polarizability43.26 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9068
Blood Brain Barrier+0.9901
Caco-2 permeable+0.7912
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.9115
Renal organic cation transporterInhibitor0.7943
CYP450 2C9 substrateNon-substrate0.7981
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.5068
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.908
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.7697
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5826
Ames testNon AMES toxic0.8703
CarcinogenicityNon-carcinogens0.9528
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5395 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.906
hERG inhibition (predictor II)Inhibitor0.8384
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.15 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0002-9110000000-042dbd4f525abce007c0
GC-MS Spectrum - EI-BGC-MSsplash10-0002-9112000000-03a53f455eb75bee12b1
GC-MS Spectrum - CI-BGC-MSsplash10-00di-4539000000-9b298eff08d8aae4d50c
Mass Spectrum (Electron Ionization)MSsplash10-006t-9552000000-ea4c5c56ee4333d0815a
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/MSsplash10-00di-0009000000-72ae3160baada68a101c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-1409000000-ca7f19c9476403b237f6
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004j-8920000000-1ac0f55aa083ad77c72b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-002b-9320000000-494b15b3b671ebe76be9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-9220000000-e3e4ef2154cbee0f6852
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0109000000-0729d6c8c352282a1d00

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 / Thiophenol ethers / Alkylarylthioethers / Piperidines / 1,4-thiazines / Trialkylamines / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds
show 1 more
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Thiophenol ether / Alkylarylthioether / Piperidine / Para-thiazine / Benzenoid
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, piperidines (CHEBI:9566)

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Seeman P: Atypical neuroleptics: role of multiple receptors, endogenous dopamine, and receptor linkage. Acta Psychiatr Scand Suppl. 1990;358:14-20. [PubMed:1978482]
  2. Assie MB, Sleight AJ, Koek W: Biphasic displacement of [3H]YM-09151-2 binding in the rat brain by thioridazine, risperidone and clozapine, but not by other antipsychotics. Eur J Pharmacol. 1993 Jun 24;237(2-3):183-9. [PubMed:7689973]
  3. Dimpfel W, Spuler M, Wessel K: Different neuroleptics show common dose and time dependent effects in quantitative field potential analysis in freely moving rats. Psychopharmacology (Berl). 1992;107(2-3):195-202. [PubMed:1352051]
  4. Barth VN, Chernet E, Martin LJ, Need AB, Rash KS, Morin M, Phebus LA: Comparison of rat dopamine D2 receptor occupancy for a series of antipsychotic drugs measured using radiolabeled or nonlabeled raclopride tracer. Life Sci. 2006 May 22;78(26):3007-12. Epub 2006 Jan 24. [PubMed:16434058]
  5. Carey GJ, Bergman J: Discriminative-stimulus effects of clozapine in squirrel monkeys: comparison with conventional and novel antipsychotic drugs. Psychopharmacology (Berl). 1997 Aug;132(3):261-9. [PubMed:9292626]
Details
2. D(1A) dopamine receptor
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. Hammock RG, Schroeder SR, Levine WR: The effect of clozapine on self-injurious behavior. J Autism Dev Disord. 1995 Dec;25(6):611-26. [PubMed:8720030]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. 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]
  2. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]
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. Andree TH, Mikuni M, Tong CY, Koenig JI, Meltzer HY: Differential effect of subchronic treatment with various neuroleptic agents on serotonin2 receptors in rat cerebral cortex. J Neurochem. 1986 Jan;46(1):191-7. [PubMed:2866233]
  2. Canton H, Verriele L, Millan MJ: Competitive antagonism of serotonin (5-HT)2C and 5-HT2A receptor-mediated phosphoinositide (PI) turnover by clozapine in the rat: a comparison to other antipsychotics. Neurosci Lett. 1994 Nov 7;181(1-2):65-8. [PubMed:7898773]
  3. Burki HR: Binding of psychoactive drugs to rat brain amine receptors, measured ex vivo, and their effects on the metabolism of biogenic amines. Naunyn Schmiedebergs Arch Pharmacol. 1986 Mar;332(3):258-66. [PubMed:2423886]
  4. Costall B, Naylor RJ: Behavioural interactions between 5-hydroxytryptophan, neuroleptic agents and 5-HT receptor antagonists in modifying rodent responding to aversive situations. Br J Pharmacol. 1995 Dec;116(7):2989-99. [PubMed:8680734]
  5. Morisset S, Sahm UG, Traiffort E, Tardivel-Lacombe J, Arrang JM, Schwartz JC: Atypical neuroleptics enhance histamine turnover in brain via 5-Hydroxytryptamine2A receptor blockade. J Pharmacol Exp Ther. 1999 Feb;288(2):590-6. [PubMed:9918563]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Milnes JT, Witchel HJ, Leaney JL, Leishman DJ, Hancox JC: hERG K+ channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656. Biochem Biophys Res Commun. 2006 Dec 8;351(1):273-80. Epub 2006 Oct 23. [PubMed:17056009]

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. 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]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Manerix (Moclobemide) Prescribing Information [Link]
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]
  2. Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J: Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010 Mar;69(3):222-30. doi: 10.1111/j.1365-2125.2009.03578.x. [PubMed:20233192]
  3. Wu Z, Lee D, Joo J, Shin JH, Kang W, Oh S, Lee do Y, Lee SJ, Yea SS, Lee HS, Lee T, Liu KH: CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob Agents Chemother. 2013 Nov;57(11):5448-56. doi: 10.1128/AAC.00843-13. Epub 2013 Aug 19. [PubMed:23959307]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. 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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Drug created on June 13, 2005 07:24 / Updated on October 18, 2018 17:02