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Identification
NameZuclopenthixol
Accession NumberDB01624  (DB08919, DB08920)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Zuclopenthixol, also known as Zuclopentixol or Zuclopenthixolum, is an antipsychotic agent. Zuclopenthixol is a thioxanthene-based neuroleptic with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. Major brands of zuclopenthixol are Cisordinol, Acuphase, and Clopixol. This drug is a liquid. This compound belongs to the 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. Known drug targets of zuclopenthixol include 5-hydroxytryptamine receptor 2A, D(1B) dopamine receptor, D(2) dopamine receptor, D(1A) dopamine receptor, and alpha-1A adrenergic receptor. It is known that zuclopenthixol is metabolized by Cytochrome P450 2D6. Zuclopenthixol was approved for use in Canada in 2011, but is not approved for use in the United States.

Structure
Thumb
Synonyms
SynonymLanguageCode
cis-ClopenthixolNot AvailableIS
ZuclopenthixolumLatinINN
ZuclopentixolSpanishINN
Salts
Name/CAS Structure Properties
Zuclopenthixol acetate
Thumb
  • InChI Key: OXAUOBQMCDIVPQ-IOXNKQMXSA-N
  • Monoisotopic Mass: 442.148176515
  • Average Mass: 443.001
DBSALT000545
Zuclopenthixol decanoate
64053-00-5
Thumb
  • InChI Key: QRUAPADZILXULG-WKIKZPBSSA-N
  • Monoisotopic Mass: 554.273377027
  • Average Mass: 555.214
DBSALT000787
Zuclopenthixol dihydrochloride
Thumb
  • InChI Key: LPWNZMIBFHMYMX-MHKBYHAFSA-N
  • Monoisotopic Mass: 472.090967307
  • Average Mass: 473.887
DBSALT000546
Brand names
NameCompany
AcuphaseH. Lundbeck A/S
Ciatyl-ZBayer Vital
CisordinolH. Lundbeck A/S
ClopixolH. Lundbeck A/S
Brand mixturesNot Available
Categories
CAS number53772-83-1
WeightAverage: 400.965
Monoisotopic: 400.137611829
Chemical FormulaC22H25ClN2OS
InChI KeyWFPIAZLQTJBIFN-DVZOWYKESA-N
InChI
InChI=1S/C22H25ClN2OS/c23-17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)27-22)5-3-9-24-10-12-25(13-11-24)14-15-26/h1-2,4-8,16,26H,3,9-15H2/b18-5-
IUPAC Name
2-(4-{3-[(9Z)-2-chloro-9H-thioxanthen-9-ylidene]propyl}piperazin-1-yl)ethan-1-ol
SMILES
OCCN1CCN(CC\C=C2\C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1
Mass Specshow(140 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzopyrans
SubclassThioxanthenes
Direct parentThioxanthenes
Alternative parentsChlorobenzenes; Aryl Chlorides; Diazinanes; Piperazines; Tertiary Amines; Primary Alcohols; Thioethers; Polyamines; Organochlorides
Substituentschlorobenzene; 1,4-diazinane; aryl halide; piperazine; benzene; aryl chloride; tertiary amine; thioether; polyamine; primary alcohol; amine; organohalogen; alcohol; organonitrogen compound; organochloride
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationUsed in the management of acute psychoses such as mania or schizophrenia. However, the use of zuclopenthixol acetate in psychiatric emergencies as an alternative to standard treatments (haloperidol, clotiapine, etc.) should be cautioned, since well executed and documented trials of zuclopenthixol acetate for this use have yet to be conducted. Zuclopenthixol acetate is not intended for long-term use.
PharmacodynamicsZuclopenthixol is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors.
Mechanism of actionZuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for alpha1-adrenergic and 5-HT2 receptors. It has weaker histamine H1 receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors.
AbsorptionUpon reaching the body water phase, the decanoate ester is slowly released from the oil depot, which is resultantly hydrolyzed to the active substance, zuclopenthixol. The decanoate ester provides a means of slow release since zuclopenthixol itself is a short-acting drug.
Volume of distribution

20 L/kg.

Protein binding98-99%
Metabolism

The metabolism of zuclopenthixol is mainly by sulphoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are devoid of pharmacological activity.

Route of eliminationPrimarily in the feces with approximately 10% in the urine.
Half life20 hours (range 12-28 hours) for the tablet form, 19 days for the depot form.
Clearance

approximately 0.9 L/min.

ToxicityAlthough there have not been any cases of overdosage reported, the symptoms are likely to be somnolence, coma, extrapyramidal symptoms, convulsions, hypotension, shock, or hyper- or hypothermia. Neuroleptic malignant syndrome may occur. Zuclopenthixol may potentiate anticholinergic effects of concurrent medications. Zuclopenthixol has a demonstrated antiemetic effect in animals, and may mask signs of toxicity due to other drug overdoses, or may mask symptoms of disease.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9443
Blood Brain Barrier + 0.9676
Caco-2 permeable - 0.5313
P-glycoprotein substrate Substrate 0.8762
P-glycoprotein inhibitor I Inhibitor 0.8736
P-glycoprotein inhibitor II Inhibitor 0.7439
Renal organic cation transporter Inhibitor 0.5829
CYP450 2C9 substrate Non-substrate 0.7898
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Non-substrate 0.6722
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Inhibitor 0.7518
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8213
Ames test Non AMES toxic 0.7617
Carcinogenicity Non-carcinogens 0.9029
Biodegradation Not ready biodegradable 0.9954
Rat acute toxicity 2.8877 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.6099
hERG inhibition (predictor II) Inhibitor 0.7023
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionIntramuscular200mg/mL
InjectionIntramuscular50mg/mL
TabletOral10 mg
TabletOral25 mg
Prices
Unit descriptionCostUnit
Clopixol Acuphase 50 mg/ml16.52USDml
Clopixol Depot 200 mg/ml16.52USDml
Clopixol 25 mg Tablet1.06USDtablet
Clopixol 10 mg Tablet0.42USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point~50http://www.lundbeck.com/upload/ca/en/files/pdf/product_monograph/Clopixol_PM_MKT_ctrl_148975_13SEPT2011_CLN_eng.pdf
water solubilityslighthttp://www.lundbeck.com/upload/ca/en/files/pdf/product_monograph/Clopixol_PM_MKT_ctrl_148975_13SEPT2011_CLN_eng.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0026ALOGPS
logP4.46ALOGPS
logP4.22ChemAxon
logS-5.2ALOGPS
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 Count5ChemAxon
Refractivity127 m3·mol-1ChemAxon
Polarizability45.29 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Khalifa AE: Zuclopenthixol facilitates memory retrieval in rats: possible involvement of noradrenergic and serotonergic mechanisms. Pharmacol Biochem Behav. 2003 Jul;75(4):755-62. Pubmed
  2. Fond G, Macgregor A, Tamouza R, Hamdani N, Meary A, Leboyer M, Dubremetz JF: Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate. Eur Arch Psychiatry Clin Neurosci. 2013 Jun 15. Pubmed
  3. Jayakody K, Gibson RC, Kumar A, Gunadasa S: Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. Cochrane Database Syst Rev. 2012 Apr 18;4:CD000525. doi: 10.1002/14651858.CD000525.pub3. Pubmed
  4. Nielsen MK, Johansen SS: Simultaneous determination of 25 common pharmaceuticals in whole blood using ultra-performance liquid chromatography-tandem mass spectrometry. J Anal Toxicol. 2012 Sep;36(7):497-506. doi: 10.1093/jat/bks054. Epub 2012 Jun 19. Pubmed
  5. Khalifa AE: Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats. Hum Exp Toxicol. 2004 Aug;23(9):439-45. Pubmed
  6. Hood S, Orr K, Bennett L, Davies S: Severe laryngeal dystonia in a patient receiving zuclopenthixol “Acuphase” and fluoxetine. Australas Psychiatry. 2010 Apr;18(2):174-6. doi: 10.3109/10398560903473686. Pubmed
  7. http://medicaid.alabama.gov/documents/2.0_Newsroom/2.4_Procurement/2.4.3_Pharm_Support_ITB/2.4.3_Antipsychotic_Agents_Class_Review_8-10-11.pdf
  8. http://www.mentalhealth.com/drug/p30-z03.html
External Links
ResourceLink
KEGG DrugD03556
PubChem Compound5311507
PubChem Substance46507341
ChemSpider4470984
Therapeutic Targets DatabaseDAP000845
PharmGKBPA452629
Drug Product Database2230402
Drugs.comhttp://www.drugs.com/international/zuclopenthixol.html
WikipediaZuclopenthixol
ATC CodesN05AF05
AHFS Codes
  • 281608
PDB EntriesNot Available
FDA labelshow(229 KB)
MSDSshow(568 KB)
Interactions
Drug Interactions
Drug
AbarelixAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
AmantadineAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and amantadine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
AmiodaroneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
AmitriptylineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
AmoxapineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ApomorphineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Antagonism may also occur between zuclopenthixol, a dopamine D2 receptor antagonist, and apomorphine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Arsenic trioxideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
AsenapineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
AzithromycinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
BromocriptineAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and bromocriptine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
BupropionBupropion, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if bupropion is initiated, discontinued or dose changed.
ChlorpromazineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Chlorpromazine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if chlorpromazine is initiated, discontinued or dose changed.
CinacalcetCinacalcet, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if cinacalcet is initiated, discontinued or dose changed.
CisaprideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
CitalopramAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ClarithromycinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ClomipramineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
CocaineCocaine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if cocaine is initiated, discontinued or dose changed.
DasatinibAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DelavirdineDelavirdine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if delavirdine is initiated, discontinued or dose changed.
DesipramineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DisopyramideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DofetilideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DolasetronAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DomperidoneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DonepezilPossible antagonism of action
DoxepinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
DronedaroneAdditive or synergistic QTc-prolonging effects may occur. Concomitant therapy is contraindicated.
DroperidolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ErythromycinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
EscitalopramAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
EtravirineZuclopenthixol (especially oral dosage form) may experience a decrease in serum concentration when used concomitantly with etravirine. It is recommended to monitor zuclopenthixol therapy for efficacy.
FlecainideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
FluconazoleAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
FluoxetineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Fluoxetine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if fluoxetine is initiated, discontinued or dose changed.
FlupentixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
FoscarnetAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
GalantaminePossible antagonism of action
HalofantrineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
HaloperidolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
IbutilideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
IloperidoneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ImipramineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
IndapamideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
IsradipineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
L-DOPAAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and levodopa, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
LapatinibAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
LevofloxacinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
LopinavirLopinavir, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if lopinavir is initiated, discontinued or dose changed.
LoxapineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MaprotilineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
MefloquineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
MesoridazineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
MethadoneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
MethotrimeprazineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Methotrimeprazine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if methotrimeprazine is initiated, discontinued or dose changed.
MetoclopramideAdditive dopamine D2 receptor antagonism may cause dopaminergic imbalance in the nigrostriatal (dopamine D1 receptors) and striatopallidal (dopamine D2 receptors). Increased risk of extrapyramidal reactions and neuroleptic malignant syndrome. Concomitant therapy should be avoided.
MoxifloxacinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
NilotinibAdditive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided.
NorfloxacinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
NortriptylineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
OctreotideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ParoxetineParoxetine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if paroxetine is initiated, discontinued or dose changed.
PazopanibAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
PentamidineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
PerflutrenAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
PergolideAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pergolide, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed. Pergolide, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if pergolide is initiated, discontinued or dose changed.
PimozideAdditive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy is contraindicated.
PramipexoleAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pramipexole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
PramlintideMay cause additive reduction in GI motility. Use caution or consider alternate therapy.
ProbucolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ProcainamideAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
PropafenoneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ProtriptylineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
QuetiapineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
QuinidineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Quinidine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if quinidine is initiated, discontinued or dose changed.
QuinineAdditive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided.
RanolazineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
RisperidoneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
RitonavirRitonavir, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if ritonavir is initiated, discontinued or dose changed.
RomidepsinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
RopiniroleAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and ropinirole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
RotigotineAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and rotigotine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
SotalolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
SparfloxacinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
SunitinibAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Zuclopenthixol, 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.
TacrolimusAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
TelavancinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
TelithromycinAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
TerbinafineTerbinafine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if terbinafine is initiated, discontinued or dose changed.
TetrabenazineAdditive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.
ThioridazineAdditive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy is contraindicated.
ThiothixeneAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimethobenzamideTrimethobenzamide and Zuclopenthixol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TrimipramineAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
TriprolidineTriprolidine and Zuclopenthixol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Zuclopenthixol, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Food InteractionsNot Available

Targets

1. 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. Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, Rendtorff C, Tolvanen E: Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. Eur Neuropsychopharmacol. 1991 Dec;1(4):541-8. Pubmed
  2. Manzaneque JM, Navarro JF: An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. Methods Find Exp Clin Pharmacol. 1999 Jan-Feb;21(1):11-5. Pubmed

2. D(1B) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(1B) dopamine receptor P21918 Details

References:

  1. Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, Rendtorff C, Tolvanen E: Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. Eur Neuropsychopharmacol. 1991 Dec;1(4):541-8. Pubmed
  2. Manzaneque JM, Navarro JF: An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. Methods Find Exp Clin Pharmacol. 1999 Jan-Feb;21(1):11-5. Pubmed

3. 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. Gareri P, De Fazio P, Stilo M, Ferreri G, De Sarro G: Conventional and Atypical Antipsychotics in the Elderly : A Review. Clin Drug Investig. 2003;23(5):287-322. Pubmed
  2. Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, Rendtorff C, Tolvanen E: Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. Eur Neuropsychopharmacol. 1991 Dec;1(4):541-8. Pubmed
  3. Nyberg S, Farde L, Bartfai A, Halldin C: Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans. Int Clin Psychopharmacol. 1995 Nov;10(4):221-7. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

References:

  1. Khalifa AE: Zuclopenthixol facilitates memory retrieval in rats: possible involvement of noradrenergic and serotonergic mechanisms. Pharmacol Biochem Behav. 2003 Jul;75(4):755-62. Pubmed

5. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Khalifa AE: Zuclopenthixol facilitates memory retrieval in rats: possible involvement of noradrenergic and serotonergic mechanisms. Pharmacol Biochem Behav. 2003 Jul;75(4):755-62. Pubmed

6. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Nyberg S, Farde L, Bartfai A, Halldin C: Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans. Int Clin Psychopharmacol. 1995 Nov;10(4):221-7. Pubmed
  2. Gjerden P, Slordal L, Bramness JG: Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents. Eur J Clin Pharmacol. 2009 Jul 31. Pubmed
  3. Khalifa AE: Zuclopenthixol facilitates memory retrieval in rats: possible involvement of noradrenergic and serotonergic mechanisms. Pharmacol Biochem Behav. 2003 Jul;75(4):755-62. Pubmed

7. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

http://www.lundbeck.com/upload/ca/en/files/pdf/product_monograph/Clopixol_PM_MKT_ctrl_148975_13SEPT2011_CLN_eng.pdf


Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

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Drug created on August 29, 2007 14:18 / Updated on November 24, 2014 14:45