Flupentixol
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- Approved, Investigational, Withdrawn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
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Chronic schizophrenia •••••••••••• ••••• •• •••• •••••••••••••• •• ••••••••••• •••••••••• •• ••••••••••••• •••••••••• •••••• Management of Depression •••••••••••• ••••• •••••• Used in combination to manage Depression Combination Product in combination with: Melitracen (DB13384) •••••••••••• ••••• ••••••• •••••••• •••••• Used in combination to manage Depression Combination Product in combination with: Melitracen (DB13384) •••••••••••• ••••• •••••• Used in combination to manage Dysphoria Combination Product in combination with: Melitracen (DB13384) •••••••••••• ••••• ••••••••• •••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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
Target Actions Organism ADopamine D2 receptor antagonistHumans ADopamine D1 receptor antagonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans UAlpha-1A adrenergic receptor antagonistHumans UDopamine D3 receptor antagonistHumans UDopamine D4 receptor antagonistHumans U5-hydroxytryptamine receptor 2C antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.15
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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Flupentixol is combined with 1,2-Benzodiazepine. Acebutolol Acebutolol may increase the orthostatic hypotensive activities of Flupentixol. Aceclofenac The risk or severity of hypertension can be increased when Flupentixol is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Flupentixol is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Flupentixol is combined with Acenocoumarol. - 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
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Flupentixol decanoate 3B2FE28C1W 30909-51-4 UIKWDDSLMBHIFT-UHFFFAOYSA-N Flupentixol dihydrochloride 96L0Z069N1 51529-01-2 IOVDQEIIMOZNNA-MHKBYHAFSA-N - International/Other Brands
- Depixol (Lundbeck A/S) / Fluanxol (Lundbeck A/S) / Jexit (Johnson)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fluanxol 0.5mg - Tab Tablet 0.5 mg Oral Lundbeck Inc. 1995-12-31 Not applicable Canada Fluanxol 3mg - Tab Tablet 3 mg Oral Lundbeck Inc. 1995-12-31 Not applicable Canada Fluanxol Depot 10%- Liq Im 100mg/ml Solution 100 mg / mL Intramuscular Lundbeck Inc. 1995-12-31 Not applicable Canada Fluanxol Depot 2% -liq Im 20mg/ml Solution 20 mg / mL Intramuscular Lundbeck Inc. 1995-12-31 Not applicable Canada Fluanxol Depot Inj 100mg/ml Liquid 100 mg / mL Intramuscular Merrell Dow Pharmaceuticals (Canada) Inc., Division Of Mmdc 1981-12-31 1996-09-09 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ANXISET Flupentixol (0.5 MG) + Melitracen (10 MG) Tablet, film coated Oral บริษัท ยูเนียนเมดดิคอล (ประเทศไทย) จำกัด 2014-06-13 Not applicable Thailand DEANXIT Flupentixol (0.5 MG) + Melitracen (10 MG) Tablet, sugar coated Oral บริษัท บี.เอ็ล.ฮั้ว จำกัด 1985-02-13 Not applicable Thailand Deanxit - Filmtabletten Flupentixol (0.5 mg) + Melitracen (10 mg) Tablet, film coated Oral Lundbeck Austria Gmb H 1971-01-13 Not applicable Austria DEANXIT TABLET Flupentixol (0.5 mg) + Melitracen (10 mg) Tablet, film coated Oral LUNDBECK SINGAPORE PTE. LTD. 1988-09-05 Not applicable Singapore DORMIR TABLET, 20 ADET Flupentixol (0.5 mg) + Melitracen (10 mg) Tablet OSEL İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey
Categories
- ATC Codes
- N05AF01 — Flupentixol
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents producing tachycardia
- Agents that produce hypertension
- Anticholinergic Agents
- Antidepressive Agents
- Antipsychotic Agents
- Antipsychotic Agents (First Generation [Typical])
- Central Nervous System Agents
- Central Nervous System Depressants
- Dopamine Agents
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Drugs causing inadvertant photosensitivity
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- Muscarinic Antagonists
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- P-glycoprotein inhibitors
- Photosensitizing Agents
- Piperazines
- Psycholeptics
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Sulfur Compounds
- Thioxanthene Derivatives
- Thioxanthenes
- Tranquilizing Agents
- Xanthenes
- 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
- 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]
- Hyttel J: Flupentixol and dopamine receptor selectivity. Psychopharmacology (Berl). 1981;75(2):217. doi: 10.1007/BF00432192. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Lundbeck Canada Inc. Product Monograph: FLUANXOL (Flupentixol), as oral tablets or intramuscular injection [Link]
- MP Biomedicals Australasia Pty Limited: cis(Z)-FLUPENTHIXOL Material Safety Data Sheet [Link]
- Summary of Product Characteristics: Deanxit (flupentixol and melitracen) oral tablets [Link]
- Package Leaflet: Fluanxol (flupentixol) oral tablets [Link]
- British Pharmacopoeia: Flupentixol Hydrochloride Safety data sheet [Link]
- External Links
- KEGG Drug
- D01044
- KEGG Compound
- C11191
- PubChem Compound
- 5281881
- PubChem Substance
- 46507816
- ChemSpider
- 4445173
- BindingDB
- 79172
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Antipsychotic Agents / Central Nervous System Disorder / Clinical Therapy / Flupentixol / Olanzapine / Quetiapine / Schizophrenia; Psychosis / Syndrome, Metabolic 1 4 Completed Treatment Compliance / Depression / Dyspepsia 1 4 Completed Treatment Emotional Disorders / Neurological Disorders 1 4 Completed Treatment Schizophrenia 1 4 Completed Treatment Tinnitus 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, sugar coated Oral Tablet Tablet Oral 5 mg Tablet Oral 0.25 mg Tablet, sugar coated Oral 0.5 MG Tablet, film coated Oral 0.5 MG Tablet, film coated Oral 1 MG Tablet Oral 1 mg Tablet, sugar coated Oral 2 MG Tablet, sugar coated Oral 5 MG Tablet, film coated Oral 5 MG Injection, solution Parenteral 100 mg Solution Intramuscular 100 mg / mL Injection, solution Parenteral 100 MG/ML Injection, solution Intramuscular 100 mg/ml Injection, solution Parenteral 20 mg Solution Intramuscular 20 mg / mL Injection, solution Parenteral 20 MG/1ML Solution Intramuscular 20 mg/ml Liquid Intramuscular 100 mg / mL Liquid Intramuscular 20 mg / mL Injection Intramuscular Injection Intramuscular 20 mg/ml Injection, solution Parenteral 100 MG/1ML Injection, solution Parenteral 10 MG/0.5ML Tablet Oral 0.5 mg Tablet Oral 3 mg Tablet, film coated Oral Injection, solution Parenteral 200 MG Injection, solution Parenteral 20 MG/ML Injection, solution Parenteral 40 MG/ML Tablet, film coated Oral Tablet, film coated Oral 3 mg Solution Intramuscular 20 mg/1ml Tablet, sugar coated Oral 3 mg - Prices
Unit description Cost Unit Fluanxol Depot 100 mg/ml 39.79USD ml Fluanxol Depot 20 mg/ml 7.96USD ml Fluanxol 3 mg Tablet 0.59USD tablet Fluanxol 0.5 mg Tablet 0.27USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 233-234 MSDS of cis(Z)-flupenthixol logP 4.51 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.00399 mg/mL ALOGPS logP 4.56 ALOGPS logP 4.5 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 15.59 Chemaxon pKa (Strongest Basic) 8.43 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 26.71 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 128.17 m3·mol-1 Chemaxon Polarizability 44.79 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9825 Blood Brain Barrier + 0.9778 Caco-2 permeable - 0.5438 P-glycoprotein substrate Substrate 0.8762 P-glycoprotein inhibitor I Inhibitor 0.92 P-glycoprotein inhibitor II Inhibitor 0.859 Renal organic cation transporter Inhibitor 0.5065 CYP450 2C9 substrate Non-substrate 0.8084 CYP450 2D6 substrate Substrate 0.804 CYP450 3A4 substrate Non-substrate 0.6921 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8933 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Inhibitor 0.5657 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7748 Ames test Non AMES toxic 0.828 Carcinogenicity Non-carcinogens 0.8985 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.8385 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6624 hERG inhibition (predictor II) Inhibitor 0.7962
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0000900000-51078530b2f9304759ec Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0000900000-a3e55e47b1a20ee56fcc Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4r-0139600000-ac84d737ec6445307da7 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0ue9-0003900000-8d09b2c9dda393230a34 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05i9-1229600000-d7c7b376787f28f39b3e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0019100000-e53e26ec20bf8ecdc874 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.54948 predictedDeepCCS 1.0 (2019) [M+H]+ 195.90749 predictedDeepCCS 1.0 (2019) [M+Na]+ 202.57454 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [Article]
- 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]
- 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]
- 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]
- 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]
- 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
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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]
- 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
- 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
- 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]
- 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
- 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
- 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
- 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
- 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
- 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
- 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]
- 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
- 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]
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
- 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]
- 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]
- 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]
- 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 February 20, 2024 23:55