Identification

Summary

Flupentixol is a thioxanthene neuroleptic used to treat schizophrenia and depression.

Brand Names
Fluanxol
Generic Name
Flupentixol
DrugBank Accession Number
DB00875
Background

Flupentixol is an antipsychotic drug of the thioxanthene group. It exists in two geometric isomers, the trans(E) and pharmacologically active cis(Z) forms. Flupentixol decanoate is one of the active ingredients found in injectable drug formulations: it is produced by esterification of cis(Z)‐flupentixol with decanoic acid.1 Flupentixol is an antagonist of both D1 and D2 dopamine receptors.1

Available as oral tablets or long-acting intramuscular injections, flupentixol is marketed under brand names such as Depixol and Fluanxol. It is approved for use in Canada and other countries around the world, but not in the US. It is used for the management of chronic schizophrenia in patients whose main manifestations do not include excitement, agitation or hyperactivity.11 It has been marketed to manage symptoms of depression in patients who may or may not exhibit signs of anxiety.14 In combination with melitracen, flupentixol is used to manage symptoms of anxiety, depression, and asthenia.13

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Thumb
Weight
Average: 434.52
Monoisotopic: 434.163969096
Chemical Formula
C23H25F3N2OS
Synonyms
  • Flupenthixol
  • Flupenthixole
  • Flupentixol
  • Flupentixolo
  • Flupentixolum
External IDs
  • FX 703
  • LC 44
  • LC-44
  • LU 5-110
  • N 7009
  • N-7009

Pharmacology

Indication

Flupentixol is indicated for maintenance therapy of chronic schizophrenic patients whose main manifestations do not include excitement, agitation or hyperactivity.11

It is indicated for the management of depression in adult patients who may, or may not, also be showing signs of anxiety.14

Flupentixol in combination with melitracen is indicated to manage symptoms of anxiety, depression, and asthenia in adults.13

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Flupentixol is an antipsychotic agent with anxiolytic and mild sedative actions. It exerts weak anticholinergic and adrenergic effects. It possesses antiemetic actions. As flupentixol works by antagonizing dopamine actions, it can cause extrapyramidal effects,11 mostly at doses greater than 10 mg. In clinical trials, flupentixol-induced extrapyramidal effects have been managed with anti-Parkinsonian drugs.3 Drug esterification in the intramuscular formulation of the drug results in slow release of the drug from the injection site and a prolonged duration of action.11 Flupentixol has been investigated for use in mild to moderate depression: compared to other antidepressant agents, flupentixol has a rapid onset of action, where antidepressive effects were observed within the first two to three days after administration.3

As with other antipsychotic agents, flupentixol can cause QTc prolongation and increase the risk of arrhythmias. In clinical trials, flupentixol was associated with the risk of cardiovascular disease, cerebrovascular adverse events, stroke, and venous thromboembolism. Flupentixol can elevate the levels of prolactin; however, the clinical significance of hyperprolactinemia caused by neuroleptic drugs is unclear. Long-term hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone mineral density in both female and male subjects.11

Interestingly, recent studies show that flupentixol exhibits anti-tumour properties alone or synergistically with other anticancer drugs like gefitinib. One study demonstrated that in vitro, flupentixol docks to the ATP binding pocket of phosphatidylinositol 3-kinase (PI3K), a lipid kinase that activates signalling pathways that are often hyperactivated in some cancers. Flupentixol inhibited the PI3K/AKT pathway and survival of lung cancer cells in vitro and in vivo.5

Mechanism of action

The mechanism of action of flupentixol is not completely understood. The antipsychotic actions are mainly thought to arise from cis(Z)-flupentixol, the active stereoisomer, acting as an antagonist at both dopamine D1 and D2 receptors with equal affinities.2 Schizophrenia is a mental illness characterized by positive (such as hallucinations and delusions) and negative (such as affect flattening and apathy) symptoms. While several neurotransmitter systems are implicated in the pathophysiologic processes leading to the development of symptoms, the dopamine and glutamate systems have been extensively studied. It is generally understood that positive symptoms of schizophrenia arise from a dysregulated striatal dopamine pathway, leading to hyperstimulation of D2 receptors. Many antipsychotic agents work by blocking D2 receptors as antagonists;7 similarly, cis(Z)-flupentixol, the active stereoisomer, is an antagonist at D2 receptors.2 However, there is now evidence that antipsychotic agents can work by blocking other dopamine receptor subtypes, such as D1, D3, or D4 receptors.6,9,10 One study showed that cis(Z)-flupentixol is an antagonist at both dopamine D1 and D2 receptors with equal affinities,2 and binds to D3 and D4 receptors with lower affinities. It also binds to alpha-1 adrenoceptors.1 Antidepressant effects of flupentixol are understood to be mediated by antagonism at 5-HT2A receptors, which are commonly downregulated following repeated antidepressant treatment.8 Flupentixol also binds to 5-HT2C receptors.1

TargetActionsOrganism
ADopamine D2 receptor
antagonist
Humans
ADopamine D1 receptor
antagonist
Humans
A5-hydroxytryptamine receptor 2A
antagonist
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
UDopamine D3 receptor
antagonist
Humans
UDopamine D4 receptor
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
UMuscarinic acetylcholine receptor M1
antagonist
Humans
Absorption

Following oral administration, flupentixol is readily absorbed from the gastrointestinal tract, with oral bioavailability of about 40%. Tmax ranges from three to eight hours. Steady-state plasma levels are achieved in about seven days and following once-daily oral administration of 5 mg flupentixol, the mean minimum steady-state level was about 1.7 ng/mL (3.9 nmol/L).11

From the site of intramuscular injection, esterified flupentixol diffuses slowly from the oil solution and is slowly released into the extracellular fluid and the circulation to be distributed to different tissues. Peak drug concentrations are reached between four and seven days following intramuscular injection. Intramuscularly administered flupentixol is detectable in the blood three weeks after injection and reaches steady-state concentrations after about three months of repeated administration.11

Volume of distribution

The apparent volume of distribution is about 14.1 L/kg. Following administration, the highest levels of flupentixol are found in the lungs, liver, and spleen. Lower concentrations of the drug are found in the blood and brain.11

Protein binding

Flupentixol is 99% bound to plasma proteins.11

Metabolism

Flupentixol is metabolized in the liver via sulfoxidation, dealkylation, and glucuronidation to form pharmacologically inactive metabolites. Flupentixol decanoate, the active ingredient in the intramuscular formulation, is hydrolyzed to flupentixol.11

Hover over products below to view reaction partners

Route of elimination

Fecal excretion is more predominant than renal excretion. In the feces, flupentixol is recovered in the feces mainly as the unchanged form, as well as its lipophilic metabolites, such as dealkyl-flupentixol. Flupentixol is recovered in the urine as the unchanged form as well as its hydrophilic sulfoxide and glucuronide metabolites.11

Half-life

The elimination half-life is about 35 hours following oral administration and three weeks following intramuscular administration.11

Clearance

Following oral administration, the mean systemic clearance is about 0.29 L/min.11

Adverse Effects
Adverseeffects
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Toxicity

The oral LD50 is 423 mg/kg in mice and 791 mg/kg in rats.12 The intravenous LD50 is 37 mg/kg in rats.[L31873]

Flupentixol overdose is characterized by sedation, frequently preceded by extreme agitation, excitement, confusion, somnolence, coma, convulsions, and hyperthermia or hypothermia. Extrapyramidal symptoms or respiratory and circulatory collapse may be observed. ECG changes, QT prolongation, Torsades de Pointes, cardiac arrest and ventricular arrhythmias have been reported from the combined use of drugs known to affect the heart with large doses of flupentixol. In case of overdose, symptomatic treatment should be initiated with airway management. In case of severe hypotension, epinephrine should not be used: instead, intravenous vasopressor drugs, such as levarterenol, can be used. Antiparkinsonian medication should be administered only if extrapyramidal symptoms develop. Gastric lavage should be initiated in the case of flupentixol tablet overdose. Further injections of flupentixol should be discontinued in case of an intramuscularly-administered drug overdose until the patient shows signs of relapse, in which the dosage can subsequently be decreased.11

Neuroleptic malignant syndrome is associated with neuroleptic drugs, which should be responded to with immediate discontinuation of the drug and initiation of symptomatic treatment and medical monitoring.11

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-Benzodiazepine1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Flupentixol.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Flupentixol.
AceclofenacThe risk or severity of hypertension can be increased when Flupentixol is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Flupentixol is combined with Acemetacin.
AcenocoumarolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Acenocoumarol.
AcetazolamideAcetazolamide may increase the central nervous system depressant (CNS depressant) activities of Flupentixol.
AcetophenazineAcetophenazine may increase the central nervous system depressant (CNS depressant) activities of Flupentixol.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Flupentixol is combined with Acetylsalicylic acid.
AclidiniumThe risk or severity of adverse effects can be increased when Flupentixol is combined with Aclidinium.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Flupentixol.
Interactions
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Food Interactions
  • Avoid alcohol. Flupentixol can enhance the sedative effects of alcohol.
  • Take with or without food. Food has negligible effects on drug pharmacokinetics.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Flupentixol decanoate3B2FE28C1W30909-51-4UIKWDDSLMBHIFT-UHFFFAOYSA-N
Flupentixol dihydrochloride96L0Z069N151529-01-2IOVDQEIIMOZNNA-MHKBYHAFSA-N
International/Other Brands
Depixol (Lundbeck A/S) / Fluanxol (Lundbeck A/S) / Jexit (Johnson)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Fluanxol 0.5mg - TabTablet0.5 mgOralLundbeck Inc.1995-12-31Not applicableCanada flag
Fluanxol 3mg - TabTablet3 mgOralLundbeck Inc.1995-12-31Not applicableCanada flag
Fluanxol Depot 10%- Liq Im 100mg/mlSolution100 mg / mLIntramuscularLundbeck Inc.1995-12-31Not applicableCanada flag
Fluanxol Depot 2% -liq Im 20mg/mlSolution20 mg / mLIntramuscularLundbeck Inc.1995-12-31Not applicableCanada flag
Fluanxol Depot Inj 100mg/mlLiquid100 mg / mLIntramuscularMerrell Dow Pharmaceuticals (Canada) Inc., Division Of Mmdc1981-12-311996-09-09Canada flag
Fluanxol Depot Inj 20mg/mlLiquid20 mg / mLIntramuscularMerrell Dow Pharmaceuticals (Canada) Inc., Division Of Mmdc1981-12-311996-09-09Canada flag
Fluanxol Tab 0.5mgTablet0.5 mgOralMerrell Dow Pharmaceuticals (Canada) Inc., Division Of Mmdc1986-12-311996-09-09Canada flag
Fluanxol Tab 3mgTablet3 mgOralMerrell Dow Pharmaceuticals (Canada) Inc., Division Of Mmdc1986-12-311996-09-09Canada flag
Flupentixol Decanoate Injection BPSolution100 mg / mLIntramuscularSandoz Canada Incorporated2009-08-272021-04-08Canada flag
Flupentixol Decanoate Injection BPSolution20 mg / mLIntramuscularSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ANXISETFlupentixol (0.5 MG) + Melitracen (10 MG)Tablet, film coatedOralบริษัท ยูเนียนเมดดิคอล (ประเทศไทย) จำกัด2014-06-13Not applicableThailand flag
DEANXITFlupentixol (0.5 MG) + Melitracen (10 MG)Tablet, sugar coatedOralบริษัท บี.เอ็ล.ฮั้ว จำกัด1985-02-13Not applicableThailand flag
DEANXIT TABLETFlupentixol (0.5 mg) + Melitracen (10 mg)Tablet, film coatedOralLUNDBECK SINGAPORE PTE. LTD.1988-05-09Not applicable
DORMIR TABLET, 20 ADETFlupentixol (0.5 mg) + Melitracen (10 mg)TabletOSEL İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
ดิพรีซอลFlupentixol (0.5 MG) + Melitracen (10 MG)Tablet, film coatedOralบริษัท เภสัชกรรมศรีประสิทธิ์ จำกัด2018-02-09Not applicableThailand flag
ฟลูเทรสFlupentixol (0.5 MG) + Melitracen (10 MG)Tablet, film coatedOralบริษัท ยูนีซัน จำกัด2016-12-29Not applicableThailand flag

Categories

ATC Codes
N05AF01 — Flupentixol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiopyrans
Sub Class
1-benzothiopyrans
Direct Parent
Thioxanthenes
Alternative Parents
Diarylthioethers / N-alkylpiperazines / Benzenoids / Trialkylamines / 1,2-aminoalcohols / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Organofluorides / Hydrocarbon derivatives
show 1 more
Substituents
1,2-aminoalcohol / 1,4-diazinane / Alcohol / Alkanolamine / Alkyl fluoride / Alkyl halide / Amine / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
thioxanthenes (CHEBI:10454)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
FA0UYH6QUO
CAS number
2709-56-0
InChI Key
NJMYODHXAKYRHW-DVZOWYKESA-N
InChI
InChI=1S/C23H25F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,29H,3,9-15H2/b18-5-
IUPAC Name
2-(4-{3-[(9Z)-2-(trifluoromethyl)-9H-thioxanthen-9-ylidene]propyl}piperazin-1-yl)ethan-1-ol
SMILES
[H]\C(CCN1CCN(CCO)CC1)=C1/C2=CC=CC=C2SC2=C1C=C(C=C2)C(F)(F)F

References

Synthesis Reference

Smith Kline & French Laboratories; British Patent 925,538; May 8, 1963. Craig, P.N. and Zirkle, C.L.; U.S. Patent 3,282,930; November 1, 1966; assigned to Smith Kline & French Laboratories.

General References
  1. Mahapatra J, Quraishi SN, David A, Sampson S, Adams CE: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD001470. doi: 10.1002/14651858.CD001470.pub2. [Article]
  2. Hyttel J: Flupentixol and dopamine receptor selectivity. Psychopharmacology (Berl). 1981;75(2):217. doi: 10.1007/BF00432192. [Article]
  3. Poldinger W, Sieberns S: Depression-inducing and antidepressive effects of neuroleptics. Experiences with flupenthixol and flupenthixol decanoate. Neuropsychobiology. 1983;10(2-3):131-6. doi: 10.1159/000117999. [Article]
  4. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [Article]
  5. Dong C, Chen Y, Li H, Yang Y, Zhang H, Ke K, Shi XN, Liu X, Li L, Ma J, Kung HF, Chen C, Lin MC: The antipsychotic agent flupentixol is a new PI3K inhibitor and potential anticancer drug for lung cancer. Int J Biol Sci. 2019 Jun 2;15(7):1523-1532. doi: 10.7150/ijbs.32625. eCollection 2019. [Article]
  6. Strange PG: Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev. 2001 Mar;53(1):119-33. [Article]
  7. Laruelle M, Frankle WG, Narendran R, Kegeles LS, Abi-Dargham A: Mechanism of action of antipsychotic drugs: from dopamine D(2) receptor antagonism to glutamate NMDA facilitation. Clin Ther. 2005;27 Suppl A:S16-24. doi: 10.1016/j.clinthera.2005.07.017. [Article]
  8. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F: The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci. 2004 Jul;29(4):252-65. [Article]
  9. Lynch MR: Schizophrenia and the D1 receptor: focus on negative symptoms. Prog Neuropsychopharmacol Biol Psychiatry. 1992;16(6):797-832. doi: 10.1016/0278-5846(92)90102-k. [Article]
  10. Howes O, McCutcheon R, Stone J: Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol. 2015 Feb;29(2):97-115. doi: 10.1177/0269881114563634. Epub 2015 Jan 13. [Article]
  11. Lundbeck Canada Inc. Product Monograph: FLUANXOL (Flupentixol), as oral tablets or intramuscular injection [Link]
  12. MP Biomedicals Australasia Pty Limited: cis(Z)-FLUPENTHIXOL Material Safety Data Sheet [Link]
  13. Summary of Product Characteristics: Deanxit (flupentixol and melitracen) oral tablets [Link]
  14. Package Leaflet: Fluanxol (flupentixol) oral tablets [Link]
KEGG Drug
D01044
KEGG Compound
C11191
PubChem Compound
5281881
PubChem Substance
46507816
ChemSpider
4445173
BindingDB
79172
RxNav
4495
ChEBI
10454
ChEMBL
CHEMBL54661
ZINC
ZINC000029489118
Therapeutic Targets Database
DAP000026
PharmGKB
PA10268
Guide to Pharmacology
GtP Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Flupentixol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAntipsychotic Agents / Central Nervous System Diseases / Clinical Therapy / Flupentixol / Olanzapine / Quetiapine / Schizophrenia; Psychosis / Syndrome, Metabolic1
4CompletedTreatmentCompliance / Depression / Dyspepsia1
4CompletedTreatmentEmotional Disorders / Neurologic Disorders1
4CompletedTreatmentSchizophrenia1
4CompletedTreatmentTinnitus1
3CompletedTreatmentGlobus1
3TerminatedTreatmentAnxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia1
3Unknown StatusTreatmentPsychosis Nos/Other1
2CompletedTreatmentCocaine Related Disorders2
2CompletedTreatmentCocaine Related Disorders / Substance Related Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, sugar coatedOral
Tablet, film coatedOral
Tablet, film coatedOral0.5 mg
Tablet
Tablet, sugar coatedOral0.5 MG
TabletOral0.5 mg
Tablet, film coatedOral0.5 MG
Tablet, film coatedOral1 MG
Tablet, film coatedOral
Tablet, sugar coatedOral2 MG
TabletOral3 mg
Tablet, sugar coatedOral5 MG
Tablet, film coatedOral5 MG
Injection, solutionParenteral100 mg
SolutionIntramuscular100 mg / mL
Injection, solutionParenteral100 MG/ML
Injection, solutionIntramuscular
Injection, solutionParenteral20 mg
SolutionIntramuscular20 mg / mL
Injection, solutionParenteral20 MG/1ML
Injection, solutionParenteral
SolutionIntramuscular
LiquidIntramuscular100 mg / mL
LiquidIntramuscular20 mg / mL
InjectionIntramuscular
InjectionIntramuscular20 mg/ml
Injection, solutionParenteral100 MG/1ML
Injection, solutionParenteral10 MG/0.5ML
TabletOral
Injection, solutionParenteral200 MG
Injection, solutionParenteral20 MG/ML
Injection, solutionParenteral40 MG/ML
Tablet, film coatedOral3 mg
SolutionIntramuscular20 mg/1ml
Tablet, sugar coatedOral3 mg
Prices
Unit descriptionCostUnit
Fluanxol Depot 100 mg/ml39.79USD ml
Fluanxol Depot 20 mg/ml7.96USD ml
Fluanxol 3 mg Tablet0.59USD tablet
Fluanxol 0.5 mg Tablet0.27USD 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)233-234MSDS of cis(Z)-flupenthixol
logP4.51HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00399 mg/mLALOGPS
logP4.56ALOGPS
logP4.5ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)15.59ChemAxon
pKa (Strongest Basic)8.43ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.71 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity128.17 m3·mol-1ChemAxon
Polarizability44.79 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9825
Blood Brain Barrier+0.9778
Caco-2 permeable-0.5438
P-glycoprotein substrateSubstrate0.8762
P-glycoprotein inhibitor IInhibitor0.92
P-glycoprotein inhibitor IIInhibitor0.859
Renal organic cation transporterInhibitor0.5065
CYP450 2C9 substrateNon-substrate0.8084
CYP450 2D6 substrateSubstrate0.804
CYP450 3A4 substrateNon-substrate0.6921
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.5657
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7748
Ames testNon AMES toxic0.828
CarcinogenicityNon-carcinogens0.8985
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8385 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6624
hERG inhibition (predictor II)Inhibitor0.7962
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 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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [Article]
  3. Ogren SO, Hall H, Kohler C, Magnusson O, Lindbom LO, Angeby K, Florvall L: Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain. Eur J Pharmacol. 1984 Jul 20;102(3-4):459-74. [Article]
  4. Arnt J: Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine. Eur J Pharmacol. 1995 Sep 5;283(1-3):55-62. [Article]
  5. Huettl P, Gerhardt GA, Browning MD, Masserano JM: Effects of dopamine receptor agonists and antagonists on catecholamine release in bovine chromaffin cells. J Pharmacol Exp Ther. 1991 May;257(2):567-74. [Article]
  6. Nilsson CL, Ekman A, Hellstrand M, Eriksson E: Inverse agonism at dopamine D2 receptors. Haloperidol-induced prolactin release from GH4C1 cells transfected with the human D2 receptor is antagonized by R(-)-n-propylnorapomorphine, raclopride, and phenoxybenzamine. Neuropsychopharmacology. 1996 Jul;15(1):53-61. [Article]
  7. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [Article]
Details
2. Dopamine D1 receptor
Kind
Protein
Organism
Humans
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  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. [Article]
  4. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [Article]
Kind
Protein
Organism
Humans
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. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
This is a possible target based on the general actions of drugs in the arylpiperazine drug class.
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. Li X, Murray WV, Jolliffe L, Pulito V: Novel arylpiperazines as selective alpha1-adrenergic receptor antagonists. Bioorg Med Chem Lett. 2000 May 15;10(10):1093-6. doi: 10.1016/s0960-894x(00)00169-4. [Article]
  2. Mahapatra J, Quraishi SN, David A, Sampson S, Adams CE: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD001470. doi: 10.1002/14651858.CD001470.pub2. [Article]
Kind
Protein
Organism
Humans
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 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. Mahapatra J, Quraishi SN, David A, Sampson S, Adams CE: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD001470. doi: 10.1002/14651858.CD001470.pub2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Mahapatra J, Quraishi SN, David A, Sampson S, Adams CE: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD001470. doi: 10.1002/14651858.CD001470.pub2. [Article]
Kind
Protein
Organism
Humans
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, 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. Mahapatra J, Quraishi SN, David A, Sampson S, Adams CE: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD001470. doi: 10.1002/14651858.CD001470.pub2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. Zhu MY, Juorio AV, Paterson IA, Boulton AA: Regulation of aromatic L-amino acid decarboxylase in rat striatal synaptosomes: effects of dopamine receptor agonists and antagonists. Br J Pharmacol. 1994 May;112(1):23-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Schindler R: Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents. Lipids. 2001 May;36(5):543-8. doi: 10.1007/s11745-001-0755-z. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
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. Dey S, Hafkemeyer P, Pastan I, Gottesman MM: A single amino acid residue contributes to distinct mechanisms of inhibition of the human multidrug transporter by stereoisomers of the dopamine receptor antagonist flupentixol. Biochemistry. 1999 May 18;38(20):6630-9. [Article]
  2. Ford JM, Bruggemann EP, Pastan I, Gottesman MM, Hait WN: Cellular and biochemical characterization of thioxanthenes for reversal of multidrug resistance in human and murine cell lines. Cancer Res. 1990 Mar 15;50(6):1748-56. [Article]
  3. Maki N, Hafkemeyer P, Dey S: Allosteric modulation of human P-glycoprotein. Inhibition of transport by preventing substrate translocation and dissociation. J Biol Chem. 2003 May 16;278(20):18132-9. doi: 10.1074/jbc.M210413200. Epub 2003 Mar 17. [Article]
  4. Maki N, Dey S: Biochemical and pharmacological properties of an allosteric modulator site of the human P-glycoprotein (ABCB1). Biochem Pharmacol. 2006 Jul 14;72(2):145-55. doi: 10.1016/j.bcp.2006.04.008. Epub 2006 Apr 25. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 26, 2021 21:40