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Identification
NameFluphenazine
Accession NumberDB00623  (APRD00633)
TypeSmall Molecule
GroupsApproved
Description

A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(2-Hydroxyethyl)-4-(3-(trifluoromethyl-10-phenothiazinyl)propyl)-piperazineNot AvailableNot Available
10-(3-(2-Hydroxyethyl)piperazinopropyl)-2-(trifluoromethyl)phenothiazineNot AvailableNot Available
10-(3'-(4''-(beta-hydroxyethyl)-1''-piperazinyl)-propyl)-3-trifluoromethylphenothiazineNot AvailableNot Available
2-(4-(3-[2-(Trifluoromethyl)-10H-phenothiazin-10-yl]propyl)-1-piperazinyl)ethanolNot AvailableNot Available
2-(Trifluoromethyl)-10-(3-(1-(beta-hydroxyethyl)-4-piperazinyl)propyl)phenothiazineNot AvailableNot Available
4-(3-(-Trifluoromethyl-10-phenothiazyl)-propyl)-1-piperazineethanolNot AvailableNot Available
4-(3-(2-(Trifluoromethyl)-10H-phenothiazin-10-yl)propyl)-1-piperazineethanolNot AvailableNot Available
4-(3-(2-Trifluoromethyl-10-phenothiazyl)-propyl)-1-piperazineethanolNot AvailableNot Available
FlufenazinaSpanishINN
FluorfenazineNot AvailableNot Available
FluorophenazineNot AvailableNot Available
FluorphenazineNot AvailableNot Available
FluphenazinGermanINN
FluphénazineFrenchINN
FluphenazinumLatinINN
TriflumethazineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fluphenazine Decanoateinjection, solution25 mg/mLintramuscular; subcutaneousPar Pharmaceutical, Inc.2014-07-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Fluphenazine Decanoateinjection, solution25 mg/mLintramuscular; subcutaneousAPP Pharmaceuticals, LLC2010-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Fluphenazine Decanoateinjection, solution25 mg/mLintramuscular; subcutaneousTYA Pharmaceuticals2010-12-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AnatensolBristol-Myers Squibb
Dapotum DNot Available
FludecasinTanabe Mitsubishi Pharma
FludecateRafa
FlumezinTanabe Mitsubishi Pharma
FunazineJohnson
LyogenLundbeck
Lyogen DepotLundbeck
Lyogen RetardLundbeck
MetotenHemofarm
ModecateBristol-Myers Squibb
ModitenBristol-Myers Squibb
Moditen DepoKrka
PermitilNot Available
ProlixinBristol-Myers Squibb
Brand mixtures
Brand NameIngredients
AtevalFluphenazine and Nortriptyline
DiserimFluphenazine and Bendroflumethiazide
EuphorFluphenazine and Nortriptyline
Salts
Name/CASStructureProperties
Fluphenazine decanoate
5002-47-1
Thumb
  • InChI Key: VIQCGTZFEYDQMR-UHFFFAOYSA-N
  • Monoisotopic Mass: 591.310632972
  • Average Mass: 591.771
DBSALT000776
Fluphenazine dihydrochloride
146-56-5
Thumb
  • InChI Key: MBHNWCYEGXQEIT-UHFFFAOYSA-N
  • Monoisotopic Mass: 509.128223252
  • Average Mass: 510.443
DBSALT000288
Fluphenazine enanthate
2746-81-8
Thumb
  • InChI Key: LRWSFOSWNAQHHW-UHFFFAOYSA-N
  • Monoisotopic Mass: 549.26368278
  • Average Mass: 549.691
DBSALT000777
Categories
CAS number69-23-8
WeightAverage: 437.522
Monoisotopic: 437.174867774
Chemical FormulaC22H26F3N3OS
InChI KeyPLDUPXSUYLZYBN-UHFFFAOYSA-N
InChI
InChI=1S/C22H26F3N3OS/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29/h1-2,4-7,16,29H,3,8-15H2
IUPAC Name
2-(4-{3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl}piperazin-1-yl)ethan-1-ol
SMILES
OCCN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(C=C3)C(F)(F)F)CC1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • N-alkylpiperazine
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • 1,2-aminoalcohol
  • Azacycle
  • Thioether
  • Alkanolamine
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor management of manifestations of psychotic disorders.
PharmacodynamicsFluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.
Mechanism of actionFluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9837
Blood Brain Barrier+0.975
Caco-2 permeable-0.5387
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor IInhibitor0.923
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.7669
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.7091
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateNon-inhibitor0.907
CYP450 2D6 substrateInhibitor0.8931
CYP450 2C19 substrateNon-inhibitor0.937
CYP450 3A4 substrateNon-inhibitor0.715
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7056
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8828
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8990 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9146
hERG inhibition (predictor II)Inhibitor0.8157
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Claris lifesciences ltd
  • Hospira inc
  • Teva parenteral medicines inc
  • Bristol myers squibb co
  • Apothecon inc div bristol myers squibb
  • Pharmaceutical assoc inc div beach products
  • Teva pharmaceuticals usa
  • Lannett holdings inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintramuscular; subcutaneous25 mg/mL
Prices
Unit descriptionCostUnit
Fluphenazine Omega 100 mg/ml31.2USD ml
Modecate Concentrate 100 mg/ml31.2USD ml
Pms-Fluphenazine Decanoate 100 mg/ml31.2USD ml
Fluphenazine Decanoate 25 mg/ml Solution14.0USD ml
Fluphenazine 2.5 mg/ml vial7.82USD ml
Fluphenazine Omega 25 mg/ml5.22USD ml
Prolixin 10 mg tablet3.1USD tablet
Prolixin 5 mg tablet2.38USD tablet
Fluphenazine dec 25 mg/ml vial1.92USD ml
Prolixin 2.5 mg tablet1.63USD tablet
Fluphenazine 10 mg tablet1.25USD tablet
Fluphenazine HCl 10 mg tablet1.19USD tablet
Fluphenazine 5 mg tablet0.97USD tablet
Fluphenazine HCl 5 mg tablet0.94USD tablet
Fluphenazine 2.5 mg tablet0.84USD tablet
Fluphenazine HCl 2.5 mg tablet0.79USD tablet
Fluphenazine 1 mg tablet0.55USD tablet
Fluphenazine HCl 1 mg tablet0.52USD tablet
Apo-Fluphenazine 2 mg Tablet0.24USD tablet
Apo-Fluphenazine 1 mg Tablet0.18USD tablet
Apo-Fluphenazine 5 mg Tablet0.18USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point224-226 (Salt)U.S. Patent 3,058,979
boiling point268-274 °C at 5.00E-01 mm HgPhysProp
water solubility31.1 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.36HANSCH,C ET AL. (1995)
logS-4.15ADME Research, USCD
pKa7.9EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.019 mg/mLALOGPS
logP4.4ALOGPS
logP3.97ChemAxon
logS-4.4ALOGPS
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 Count7ChemAxon
Refractivity117.27 m3·mol-1ChemAxon
Polarizability44.92 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.44 KB)
SpectraMS
References
Synthesis Reference

Ullyot, G.E.; U.S. Patent 3,058,979; October 16, 1962; assigned to Smith Kline & French
Laboratories.

US3058979
General ReferenceNot Available
External Links
ATC CodesN05AB02
AHFS Codes
  • 28:16.08.24
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmphetamineDecreased anorexic effect, may increase psychotic symptoms
AtomoxetineRisk of additive CNS depressant effects. Monitor for increased CNS depression during concomitant therapy.
BenzphetamineAntipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
BromocriptineThe phenothiazine decreases the effect of bromocriptine
CisaprideIncreased risk of cardiotoxicity and arrhythmias
DexfenfluramineDecreased anorexic effect, may increase psychotic symptoms
DextroamphetamineDecreased anorexic effect, may increase psychotic symptoms
DiethylpropionDecreased anorexic effect, may increase psychotic symptoms
FenfluramineDecreased anorexic effect, may increase psychotic symptoms
GatifloxacinIncreased risk of cardiotoxicity and arrhythmias
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
GuanethidineFluphenazine may decrease the effect of guanethidine.
LevofloxacinIncreased risk of cardiotoxicity and arrhythmias
MazindolDecreased anorexic effect, may increase psychotic symptoms
MethamphetamineDecreased anorexic effect, may increase psychotic symptoms
MetrizamideIncreased risk of convulsions
PhendimetrazineDecreased anorexic effect, may increase psychotic symptoms
PhenmetrazineDecreased anorexic effect, may increase psychotic symptoms
PhentermineDecreased anorexic effect, may increase psychotic symptoms
PhenylpropanolamineDecreased anorexic effect, may increase psychotic symptoms
SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Fluphenazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
TerbinafineTerbinafine may reduce the metabolism and clearance of Fluphenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluphenazine if Terbinafine is initiated, discontinued or dose changed.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TetrabenazineMay cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
TrimethobenzamideTrimethobenzamide and Fluphenazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineThe antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Fluphenazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Fluphenazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

Targets

1. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Van Kampen JM, Stoessl AJ: Dopamine D(1A) receptor function in a rodent model of tardive dyskinesia. Neuroscience. 2000;101(3):629-35. Pubmed
  3. Cai G, Gurdal H, Smith C, Wang HY, Friedman E: Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein. Mol Pharmacol. 1999 Nov;56(5):989-96. Pubmed
  4. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed

3. Calmodulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Calmodulin P62158 Details

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
  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
  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
  4. Nakabayashi H, Komada H, Yoshida T, Takanari H, Izutsu K: Lymphocyte calmodulin and its participation in the stimulation of T lymphocytes by mitogenic lectins. Biol Cell. 1992;75(1):55-9. Pubmed
  5. Kauss H: Sensing of Volume Changes by Poterioochromonas Involves a Ca-Regulated System Which Controls Activation of Isofloridoside-Phosphate Synthase. Plant Physiol. 1981 Aug;68(2):420-424. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 17:18