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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:33:24 UTC
HMDB IDHMDB15561
Secondary Accession NumbersNone
Metabolite Identification
Common NameZuclopenthixol
DescriptionZuclopenthixol is only found in individuals that have used or taken this drug. It is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. [PubChem]Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene group. 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.
Structure
Thumb
Synonyms
ValueSource
(Z)-4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanolChEBI
ZuclopenthixolumChEBI
ZuclopentixolChEBI
Zuclopenthixol acetateHMDB
Zuclopenthixol decanoateHMDB
Zuclopenthixol dihydrochlorideHMDB
Chemical FormulaC22H25ClN2OS
Average Molecular Weight400.965
Monoisotopic Molecular Weight400.137611829
IUPAC Name2-(4-{3-[(9Z)-2-chloro-9H-thioxanthen-9-ylidene]propyl}piperazin-1-yl)ethan-1-ol
Traditional Namezuclopenthixol
CAS Registry Number53772-83-1
SMILES
OCCN1CCN(CC\C=C2\C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1
InChI Identifier
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-
InChI KeyInChIKey=WFPIAZLQTJBIFN-DVZOWYKESA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiopyrans
Sub Class1-benzothiopyrans
Direct ParentThioxanthenes
Alternative Parents
Substituents
  • Thioxanthene
  • Diarylthioether
  • N-alkylpiperazine
  • Chlorobenzene
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Aryl halide
  • Aryl chloride
  • Tertiary aliphatic amine
  • Tertiary amine
  • 1,2-aminoalcohol
  • Azacycle
  • Thioether
  • Alkanolamine
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antipsychotic Agents
  • Dopamine Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.60e-03 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0026 mg/mLALOGPS
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 RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01624
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01624
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01624
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4470984
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkZuclopenthixol
NuGOwiki LinkHMDB15561
Metagene LinkHMDB15561
METLIN IDNot Available
PubChem Compound5311507
PDB IDNot Available
ChEBI ID51364
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General 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. [12957216 ]
  2. 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. [15497819 ]
  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. [22513898 ]
  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. [22718540 ]
  5. 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. [23771405 ]
  6. Internet Mental Health [Link]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
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. [12957216 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
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. [17535043 ]
  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. [1822319 ]
  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. [8748043 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
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. [8748043 ]
  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 Dec;65(12):1229-35. [19644682 ]
  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. [12957216 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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) proteins
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
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. [12957216 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular weight:
49292.8
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. [1822319 ]
  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. [10222441 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Gene Name:
DRD5
Uniprot ID:
P21918
Molecular weight:
52950.5
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. [1822319 ]
  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. [10222441 ]